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Zhao X, Liu Y, Wang D, Li T, Xu Z, Li Z, Bai X, Wang Y. Role of GLP‑1 receptor agonists in sepsis and their therapeutic potential in sepsis‑induced muscle atrophy (Review). Int J Mol Med 2025; 55:74. [PMID: 40052580 PMCID: PMC11936484 DOI: 10.3892/ijmm.2025.5515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Accepted: 01/17/2025] [Indexed: 03/27/2025] Open
Abstract
Sepsis‑induced myopathy (SIM) is a common complication in intensive care units, which is often associated with adverse outcomes, primarily manifested as skeletal muscle weakness and atrophy. Currently, the management of SIM focuses on prevention strategies, as effective therapeutic options remain elusive. Glucagon‑like peptide‑1 (GLP‑1) receptor agonists (GLP‑1RAs) have garnered attention as hypoglycemic and weight‑loss agents, with an increasing body of research focusing on the extrapancreatic effects of GLP‑1. In preclinical settings, GLP‑1RAs exert protective effects against sepsis‑related multiple organ dysfunction through anti‑inflammatory and antioxidant mechanisms. Based on the existing research, we hypothesized that GLP‑1RAs may serve potential protective roles in the repair and regeneration of skeletal muscle affected by sepsis. The present review aimed to explore the relationship between GLP‑1RAs and sepsis, as well as their impact on muscle atrophy‑related myopathy. Furthermore, the potential mechanisms and therapeutic benefits of GLP‑1RAs are discussed in the context of muscle atrophy induced by sepsis.
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Affiliation(s)
- Xuan Zhao
- Trauma Center, Department of Emergency and Traumatic Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Yukun Liu
- Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Dongfang Wang
- Trauma Center, Department of Emergency and Traumatic Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Tonghan Li
- Trauma Center, Department of Emergency and Traumatic Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Zhikai Xu
- Trauma Center, Department of Emergency and Traumatic Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Zhanfei Li
- Trauma Center, Department of Emergency and Traumatic Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Xiangjun Bai
- Trauma Center, Department of Emergency and Traumatic Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Yuchang Wang
- Trauma Center, Department of Emergency and Traumatic Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
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Phengpol N, Promsan S, Pengrattanachot N, Jaruan O, Sutthasupha P, Lungkaphin A. Maternal obesity promotes impaired renal autophagic process and kidney injury in male offspring. Int J Obes (Lond) 2025:10.1038/s41366-025-01751-3. [PMID: 40133698 DOI: 10.1038/s41366-025-01751-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 02/12/2025] [Accepted: 03/14/2025] [Indexed: 03/27/2025]
Abstract
BACKGROUND Obesity during pregnancy increases the risk of obesity, insulin resistance, diabetes, and the development and progression of chronic kidney disease (CKD) in later life in offspring. Impaired renal autophagic process is linked to kidney dysfunction in the setting of increased renal lipid accumulation. The aim of this study was to elucidate the effect of maternal obesity on kidney injury related to impaired renal autophagic process in the offspring. METHODS Maternal obesity model was conducted using female C57BL/6 mice fed with high-fat diet (HFD) for 8 weeks before mating. HFD was consecutively maintained throughout gestation and lactation. Male offspring were selected for investigation after weaning. Metabolic parameters and kidney morphology were performed. Renal insulin signaling, lipid metabolism, lipid accumulation, fibrosis and autophagy were determined. RESULTS Male offspring of HFD fed mothers developed obesity with insulin resistance, hyperglycemia, hyperlipidemia and consequently promoted kidney injury. Maternal obesity increased CD36, FAS, SREBP1c and Perilipin-2 while suppressed PPARα and CPT1A. The reduction of AMPK, SIRT1, Beclin-1, LC3B, and LAMP2 and the elevation of mTOR and SQSTM1/P62 were observed. These findings indicated the impairment of autophagy and renal lipid metabolism exaggerating renal lipid accumulation in the offspring of maternal obesity. CONCLUSIONS This study demonstrated that long-term HFD consumption in mothers promoted obesity with insulin resistance related kidney injury through the impairment of autophagic process and renal lipid metabolism in the offspring. These circumstances accelerated kidney injury and contributed to an increased susceptibility to CKD in male offspring of maternal obesity.
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Affiliation(s)
- Nichakorn Phengpol
- Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Sasivimon Promsan
- Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | | | - Onanong Jaruan
- Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Prempree Sutthasupha
- Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Anusorn Lungkaphin
- Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
- Functional Foods for Health and Disease, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
- Functional Food Research Center for Well-being, Multidisciplinary Research Institute Chiang Mai University, Chiang Mai, Thailand.
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Dilaver RG, Afsar RE, Crescenzi R, Gamboa J, Ikizler TA. Effects of Dulaglutide on Ectopic Fat Deposition in Chronic Kidney Disease (CKD): A Pilot and Feasibility Study (GLIMP). MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2025:2025.03.19.25324266. [PMID: 40166561 PMCID: PMC11957094 DOI: 10.1101/2025.03.19.25324266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
Introduction Patients with chronic kidney disease (CKD) often exhibit ectopic fat accumulation, including intermuscular adipose tissue (IMAT), which is associated with metabolic and muscular dysfunctions. This study aimed to evaluate the effects of dulaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), on reducing IMAT and improving metabolic and physical functions in patients with CKD stage 3-4. Methods Seven patients were recruited between April 2022 and November 2023. A 12-week dulaglutide (1.5 mg/wk) intervention was conducted with pre-and post-treatment assessments, including magnetic resonance imaging (MRI) for the IMAT evaluation and systemic physical performance battery test (SPPB) for physical performance evaluation. Their body mass indexes (BMI) were calculated and blood samples were analyzed for inflammatory and metabolic markers, including high sensitive C-reactive protein (Hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), glucose, insulin resistance (IR), total cholesterol, triglyceride, adiponectin, leptin, and leptin-adiponectin ratio (LAR) before and after treatment. Paired t-tests and Mann-Whitney U tests were used for statistical analysis, with significance set at p < 0.05. Results Out of 58 assessed patients with CKD stage 3-4, 7 were enrolled, with 5 completing the full 12-week dulaglutide treatment. The total 7 people had a mean age of 59 years, mean BMI of 31.4 kg/m², and baseline eGFR of 31.7 mL/min/1.73m². IMAT decreased in 4 patients and increased in 3 patients, with no statistically significant changes overall (p = 0.69). The quadriceps muscle cross-sectional area (CSA) also showed no significant difference (p = 0.73). BMI and serum leptin levels significantly decreased after treatment (p < 0.05), while other inflammatory and metabolic markers, and physical performance scores showed no significant changes. No serious adverse events were reported. Conclusions This study examined the effects of a 12-week dulaglutide treatment on IMAT accumulation in patients with CKD stage 3-4. While BMI significantly decreased, changes in IMAT were modest and not statistically significant, with potential but unproven clinical and metabolic benefits. Many metabolic and inflammatory markers improved, though not statistically significantly, and physical performance remained unchanged. Muscle CSA and function were maintained, which may alleviate concerns about potential GLP-1RA-induced muscle loss. Dulaglutide was well-tolerated, with minimal side effects. The small sample size and short duration highlight the need for further research. Trial Registration Name of the Registry : ClinicalTrials.gov Trial Registration Number : NCT05254418 Date of Registration : 2022-02-01.
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Zhao W, Wang X, Liu Y, Lu L, Ding Y, Zhang T. Timosaponin AⅢ inhibits ectopic lipid deposition and enhances the browning of white adipose tissue. Eur J Pharmacol 2025; 998:177506. [PMID: 40074140 DOI: 10.1016/j.ejphar.2025.177506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 02/15/2025] [Accepted: 03/10/2025] [Indexed: 03/14/2025]
Abstract
Timosaponin AⅢ(TAⅢ), derived from the Chinese medicinal herb Anemarrhena asphodeloides Bunge, has been reported to have a range of pharmacological effects including improvement of learning and memory deficits, anti-tumor, hypoglycemic effect and anti-hypertension. This study explored the therapeutic effects and preliminary mechanisms of TAⅢ in improving insulin resistance in ob/ob mice. We found that treatment with 10 mg kg-1·d-1 of TAⅢ reduced the expression of SREBPs and alleviated ectopic lipid deposition by decreasing DAG accumulation in liver. The decrease of DAG further inhibited the membrane translocation of PKC-ε, releasing its inhibition of phosphorylation at Ser307 of IRS1, and ultimately enhancing the AKT signaling response to insulin stimulation. In addition, TAⅢ promoted the browning of iWAT by activating the PGC1α-UCP1 axis on ob/ob mice, thereby enhancing fatty acid oxidation and increasing energy consumption, thus reducing its interference with insulin signaling. TAⅢ worked by enhancing the function of adipose tissue and inhibited lipid synthesis. These actions collectively ameliorated metabolic disturbances associated with insulin resistance. Therefore, we preliminarily concluded that TAⅢ improved metabolic disturbances related to insulin resistance. However, further research is needed, additional studies are necessary to validate these potential mechanisms.
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Affiliation(s)
- Wenjun Zhao
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xiaoying Wang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yun Liu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Lu Lu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yue Ding
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; National Innovation Platform for Medical Industry-Education Integration, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Tong Zhang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; National Innovation Platform for Medical Industry-Education Integration, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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Kiyoyama H, Tanabe M, Higashi M, Kamamura N, Kawano Y, Ihara K, Hideura K, Ito K. Association of visceral fat obesity with structural change in abdominal organs: fully automated three-dimensional volumetric computed tomography measurement using deep learning. Abdom Radiol (NY) 2025:10.1007/s00261-025-04834-x. [PMID: 39937214 DOI: 10.1007/s00261-025-04834-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 01/13/2025] [Accepted: 02/02/2025] [Indexed: 02/13/2025]
Abstract
The purpose of this study was to explore the association between structural changes in abdominal organs and visceral fat obesity (VFO) using a fully automated three-dimensional (3D) volumetric computed tomography (CT) measurement method based on deep learning algorithm. A total of 610 patients (295 men and 315 women; mean age, 68.4 years old) were included. Fully automated 3D volumetric CT measurements of the abdominal organs were performed to determine the volume and average CT attenuation values of each organ. All patients were divided into 2 groups based on the measured visceral fat area: the VFO group (≥ 100 cm2) and non-VFO group (< 100 cm2), and the structural changes in abdominal organs were compared between these groups. The volumes of all organs were significantly higher in the VFO group than in the non-VFO group (all of p < 0.001). Conversely, the CT attenuation values of all organs in the VFO group were significantly lower than those in the non-VFO group (all of p < 0.001). Pancreatic CT values (r = - 0.701, p < 0.001) were most strongly associated with the visceral fat, followed by renal CT values (r = - 0.525, p < 0.001) and hepatic CT values (r = - 0.510, p < 0.001). Fully automated 3D volumetric CT measurement using a deep learning algorithm has the potential to detect the structural changes in the abdominal organs, especially the pancreas, such as an increase in the volumes and a decrease in CT attenuation values, probably due to increased ectopic fat accumulation in patients with VFO. This technique may provide valuable imaging support for the early detection and intervention of metabolic-related diseases.
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Affiliation(s)
- Haruka Kiyoyama
- Department of Radiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Masahiro Tanabe
- Department of Radiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan.
| | - Mayumi Higashi
- Department of Radiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Naohiko Kamamura
- Department of Radiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Yosuke Kawano
- Department of Radiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Kenichiro Ihara
- Department of Radiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Keiko Hideura
- Department of Radiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
| | - Katsuyoshi Ito
- Department of Radiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan
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Wang LF, Li Q, Le Zhao J, Wen K, Zhang YT, Zhao QH, Ding Q, Li JH, Guan XH, Xiao YF, Deng KY, Xin HB. CD38 deficiency prevents diabetic nephropathy by inhibiting lipid accumulation and oxidative stress through activation of the SIRT3 pathway. Biochem Cell Biol 2025; 103:1-12. [PMID: 39116458 DOI: 10.1139/bcb-2024-0058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/10/2024] Open
Abstract
Diabetic nephropathy (DN) is one of the most common complications of diabetes. Our previous study showed that CD38 knockout (CD38KO) mice had protective effects on many diseases. However, the roles and mechanisms of CD38 in DN remain unknown. Here, DN mice were generated by high-fat diet (HFD) feeding plus streptozotocin (STZ) injection in male CD38KO and CD38flox mice. Mesangial cells (SV40 MES 13 cells) were used to mimic the injury of DN with palPagination Donemitic acid (PA) treatment in vitro. Our results showed that CD38 expression was significantly increased in kidney of diabetic CD38flox mice and SV40 MES 13 cells treated with PA. CD38KO mice were significantly resistant to diabetes-induced renal injury. Moreover, CD38 deficiency markedly decreased HFD/STZ-induced lipid accumulation, fibrosis, and oxidative stress in kidney tissue. In contrast, overexpression of CD38 aggravated PA-induced lipid accumulation and oxidative stress. CD38 deficiency increased expression of SIRT3, while overexpression of CD38 decreased its expression. More importantly, 3-TYP, an inhibitor of SIRT3, significantly enhanced PA-induced lipid accumulation and oxidative stress in CD38 overexpressing cell lines. In conclusion, our results demonstrated that CD38 deficiency prevented DN by inhibiting lipid accumulation and oxidative stress through activation of the SIRT3 pathway.
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Affiliation(s)
- Ling-Fang Wang
- National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, China
| | - Qian Li
- National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, China
| | - Jia Le Zhao
- National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, China
| | - Ke Wen
- National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, China
| | - Ya-Ting Zhang
- National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, China
| | - Qi-Hang Zhao
- National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, China
| | - Qi Ding
- National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, China
| | - Jia-Hui Li
- National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, China
| | - Xiao-Hui Guan
- National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, China
| | - Yun-Fei Xiao
- National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, China
| | - Ke-Yu Deng
- National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, China
| | - Hong-Bo Xin
- National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330031, China
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Bragina A, Rodionova Y, Osadchiy K, Bayutina D, Vasilchenko MK, Fomin A, Podzolkov V. Relationships of Thickness of Perirenal Fat with Urinary Levels of MCP-1 and NGAL in Patients with Hypertension. J Obes Metab Syndr 2024; 33:360-366. [PMID: 39266455 PMCID: PMC11704222 DOI: 10.7570/jomes24002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 02/26/2024] [Accepted: 05/29/2024] [Indexed: 09/14/2024] Open
Abstract
Background We conducted a study to determine the relationships between perirenal fat (PRF) thickness and urinary levels of monocyte chemoattractant protein-1 (MCP-1) and neutrophil gelatinase-associated lipocalin (NGAL) in patients with hypertension (HTN). Methods In 338 HTN patients (aged 63.5±12.3 years on average), MCP-1 and NGAL levels were studied using enzyme-linked immunosorbent assay (ELISA). To measure PRF thickness, all patients underwent CT scans. Results We considered PRF thickness ≥1.91 cm as the diagnostic threshold for perirenal obesity. Patients with excessive PRF thickness exhibited significantly lower levels of MCP-1 and NGAL compared with those with PRF thickness ≥1.91 cm: 0.98 pg/mL (interquartile range [IQR], 0.21 to 2.05) vs. 2.35 pg/mL (IQR, 0.37 to 5.22) for MCP-1 and 50.0 pg/mL (IQR, 48.9 to 67.8) vs. 98.3 pg/mL (IQR, 68.4 to 187.1) for NGAL. We found a relationship of PRF thickness with both MCP-1 (r=0.46, P<0.05) and NGAL (r=0.53, P<0.05), the levels of which were significantly different in patients with first- and third-stage chronic kidney disease: 0.33 pg/mL (IQR, 0.21 to 1.35) vs. 4.47 pg/mL (IQR, 0.23 to 10.81); 50.0 pg/mL (IQR, 49.4 to 85.5) vs. 126.45 pg/mL (IQR, 57.5 to 205.15), respectively (P=0.04). Patients with metabolically healthy obesity (MHO) had significantly lower MCP-1 levels than those with metabolically unhealthy obesity (MUO): 0.65 pg/mL (IQR, 0.21 to 2.15) vs. 3.28 pg/mL (IQR, 2.05 to 5.22) (P=0.014). MHO patients showed significantly lower NGAL levels than MUO patients: 50.0 pg/mL (IQR, 49.4 to 62.2) vs. 98.3 pg/mL (IQR, 50.0 to 174.8) (P=0.04). Multiple linear regression analysis revealed significant relationships of MCP-1 with PRF thickness (β±standard error, 0.41±0.15; P<0.001) and smoking (0.26±0.13; P=0.01) and of NGAL with age (0.45±0.16; P<0.01) and PRF thickness (0.49±0.15; P<0.001). Conclusion We identified higher concentrations of renal fibrosis markers in patients with perirenal and MUO as well as a link between PRF thickness and MCP-1 and NGAL levels in urine.
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Affiliation(s)
- Anna Bragina
- Department of Faculty Therapy No. 2, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Yulia Rodionova
- Department of Faculty Therapy No. 2, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Konstantin Osadchiy
- Department of Faculty Therapy No. 2, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Daria Bayutina
- Department of Faculty Therapy No. 2, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Maria K. Vasilchenko
- Department of Faculty Therapy No. 2, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Alexander Fomin
- Department of Faculty Therapy No. 2, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Valeriy Podzolkov
- Department of Faculty Therapy No. 2, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
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Zhang X, Wu W, Li Y, Peng Z. Exploring the role and therapeutic potential of lipid metabolism in acute kidney injury. Ren Fail 2024; 46:2403652. [PMID: 39319697 PMCID: PMC11425701 DOI: 10.1080/0886022x.2024.2403652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 09/06/2024] [Accepted: 09/06/2024] [Indexed: 09/26/2024] Open
Abstract
Acute kidney injury (AKI) is a prevalent condition, yet no specific treatment is available. Extensive research has revealed the pivotal role of lipid-related alterations in AKI. Lipid metabolism plays an essential role in the sustenance of the kidneys. In addition to their energy-supplying function, lipids contribute to the formation of renal biomembranes and the establishment of the renal microenvironment. Moreover, lipids or their metabolites actively participate in signal transduction, which governs various vital biological processes, such as proliferation, differentiation, apoptosis, autophagy, and epithelial-mesenchymal transition. While previous studies have focused predominantly on abnormalities in lipid metabolism in chronic kidney disease, this review focuses on lipid metabolism anomalies in AKI. We explore the significance of lipid metabolism products as potential biomarkers for the early diagnosis and classification of AKI. Additionally, this review assesses current preclinical investigations on the modulation of lipid metabolism in the progression of AKI. Finally, on the basis of existing research, this review proposes future directions, highlights challenges, and presents novel targets and innovative ideas for the treatment of and intervention in AKI.
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Affiliation(s)
- Xiaoyu Zhang
- Department of Critical Care Medicine, Zhongnan Hospital, Wuhan University, Wuhan, China
- Clinical Research Center of Hubei Critical Care Medicine, Wuhan, China
| | - Wen Wu
- Department of Critical Care Medicine, Zhongnan Hospital, Wuhan University, Wuhan, China
- Clinical Research Center of Hubei Critical Care Medicine, Wuhan, China
- Department of Critical Care Medicine, Yichang Central People's Hospital, Yichang, China
| | - Yiming Li
- Department of Critical Care Medicine, Zhongnan Hospital, Wuhan University, Wuhan, China
- Clinical Research Center of Hubei Critical Care Medicine, Wuhan, China
| | - Zhiyong Peng
- Department of Critical Care Medicine, Zhongnan Hospital, Wuhan University, Wuhan, China
- Clinical Research Center of Hubei Critical Care Medicine, Wuhan, China
- Department of Critical Care Medicine, Center of Critical Care Nephrology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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Yang XY, Jiang D, Wang YZ, Duan MY, Huang YW, Wang XJ, Xiang ZM, Sheng J, Zhu QQ. Chlorogenic acid alleviates renal fibrosis by reducing lipid accumulation in diabetic kidney disease through suppressing the Notch1 and Stat3 signaling pathway. Ren Fail 2024; 46:2371988. [PMID: 38952291 PMCID: PMC11221469 DOI: 10.1080/0886022x.2024.2371988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 06/19/2024] [Indexed: 07/03/2024] Open
Abstract
AIMS Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD renal fibrosis. METHODS This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing in vitro and in vivo models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein. RESULTS In vitro studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, in vivo studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was -6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1. CONCLUSION CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways.
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Affiliation(s)
- Xiao-ying Yang
- Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, China
- College of Science, Yunnan Agricultural University, Kunming, China
| | - Die Jiang
- Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, China
- College of Food Science and Technology, Yunnan Agricultural University, Kunming, China
| | - Yuan-zhu Wang
- Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, China
- College of Food Science and Technology, Yunnan Agricultural University, Kunming, China
| | - Mei-yan Duan
- Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, China
- College of Food Science and Technology, Yunnan Agricultural University, Kunming, China
| | - Ye-wei Huang
- Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, China
- State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Kunming, China
| | - Xuan-jun Wang
- Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, China
- State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Kunming, China
| | - Ze-min Xiang
- Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, China
- College of Food Science and Technology, Yunnan Agricultural University, Kunming, China
| | - Jun Sheng
- Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, China
- State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Kunming, China
| | - Qiang-qiang Zhu
- Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, China
- College of Food Science and Technology, Yunnan Agricultural University, Kunming, China
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10
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Zheng K, Qian Y, Wang H, Song D, You H, Hou B, Han F, Zhu Y, Feng F, Lam SM, Shui G, Li X. Withdrawn: Combinatorial lipidomics and proteomics underscore erythrocyte lipid membrane aberrations in the development of adverse cardio-cerebrovascular complications in maintenance hemodialysis patients. Redox Biol 2024; 76:103295. [PMID: 39159596 PMCID: PMC11378344 DOI: 10.1016/j.redox.2024.103295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 07/21/2024] [Accepted: 07/31/2024] [Indexed: 08/21/2024] Open
Abstract
This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). The authors reached out to the Publisher to alert the Publisher to incorrect text published in the article. After investigating the situation, the journal came to the conclusion that the wrong version of the file was sent by the authors to the production team during the proof stage and the misplaced text was not noticed by the authors when they approved the final version. After consulting with the Editor-in-Chief of the journal, the decision was made to withdraw the current version of the article.
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Affiliation(s)
- Ke Zheng
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Yujun Qian
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China; Department of Nephrology, Jiangsu Province Hospital/The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Haiyun Wang
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Dan Song
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Hui You
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Bo Hou
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Fei Han
- Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Yicheng Zhu
- Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Feng Feng
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Sin Man Lam
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
| | - Guanghou Shui
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
| | - Xuemei Li
- Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
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11
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Dhondge RH, Agrawal S, Patil R, Kadu A, Kothari M. A Comprehensive Review of Metabolic Syndrome and Its Role in Cardiovascular Disease and Type 2 Diabetes Mellitus: Mechanisms, Risk Factors, and Management. Cureus 2024; 16:e67428. [PMID: 39310549 PMCID: PMC11416200 DOI: 10.7759/cureus.67428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 08/21/2024] [Indexed: 09/25/2024] Open
Abstract
Metabolic syndrome is a multifaceted metabolic disorder characterized by a constellation of interconnected risk factors, including insulin resistance, abdominal obesity, dyslipidemia, and hypertension. These components collectively predispose individuals to an elevated risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The prevalence of metabolic syndrome has escalated globally, paralleling the rise in obesity rates and sedentary lifestyles. This review explores the pathophysiology underlying metabolic syndrome, emphasizing its role in the development and progression of CVD and T2DM. Epidemiological data underscore the substantial public health burden metabolic syndrome poses, necessitating effective preventive strategies and management approaches. The current diagnostic criteria and screening tools are discussed, highlighting their utility in clinical practice. Management strategies encompass lifestyle modifications, pharmacotherapy, and surgical interventions, each targeting specific components of metabolic syndrome to mitigate cardiovascular and metabolic risks. The challenges in diagnosing and managing metabolic syndrome are addressed alongside emerging research directions to enhance prevention and treatment outcomes. By elucidating the intricate relationship between metabolic syndrome, CVD, and T2DM, this review aims to guide healthcare practitioners in optimizing patient care and advancing public health initiatives to combat this pervasive syndrome.
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Affiliation(s)
- Rushikesh H Dhondge
- General Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Sachin Agrawal
- General Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Rajvardhan Patil
- General Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Ajinkya Kadu
- General Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Manjeet Kothari
- General Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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12
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Feng Q, Zhang Y, Wang Z, Yang P, Zhang Y, Fu B. A study of baseline data from SPRINT: Exploring lipid profile changes in middle-aged and elderly patients. Lipids 2024; 59:101-109. [PMID: 38741514 DOI: 10.1002/lipd.12396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Revised: 02/26/2024] [Accepted: 04/15/2024] [Indexed: 05/16/2024]
Abstract
The elderly population is at a higher risk of cardiovascular complications, and dyslipidemia plays a significant role as a contributing factor. Chronic kidney disease (CKD) patients are prone to lipid abnormalities, further increasing the risk of cardiovascular complications. We aimed to investigate the lipid profile characteristics of the middle-aged and elderly population, particularly CKD patients. We conducted a cross-sectional study using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT). It was examined how lipid profiles are affected by age within the general population, and how BMI and lipid characteristics are affected by CKD subtype. Among 8746 participants, we observed a decreasing trend in LnTAG (natural logarithm of Triacylglycerol) and total Cholesterol (CHR) levels with increasing age, while high-density lipoprotein cholesterol (HDL-C) levels increased with age. In the CKD and non-CKD subgroups created through propensity score matching based on age, sex, and race, CKD individuals exhibited significantly higher average LnTAG levels across all age groups compared to the non-CKD group. Multivariable linear regression analysis, controlling for confounding variables, revealed a negative correlation between LnTAG and estimated glomerular filtration rate (eGFR) (r = -0.002, p < 0.001). HDL-C showed a positive correlation with eGFR (r = 0.001, p < 0.001). [Correction added on 1 July 2024, after first online publication: The value of r in the preceding sentence has been updated to r = 0.001.] That is, in the middle-aged and elderly population, age demonstrated a negative correlation with total CHR and TAG levels, while exhibiting a positive correlation with HDL-C levels. CKD patients exhibited relatively higher TAG levels, which were positively associated with CKD progression.
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Affiliation(s)
- Qun Feng
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yanzhi Zhang
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Zijuan Wang
- Department of Nephrology, Tianjin Jizhou District Traditional Chinese Medicine Hospital, Tianjin, China
| | - Peng Yang
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yu Zhang
- Department of Nephrology and Rheumatology, Second Hospital Affiliated to Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Bin Fu
- Department of Nephrology and Rheumatology, Second Hospital Affiliated to Tianjin University of Traditional Chinese Medicine, Tianjin, China
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13
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Mao TH, Huang HQ, Zhang CH. Clinical characteristics and treatment compounds of obesity-related kidney injury. World J Diabetes 2024; 15:1091-1110. [PMID: 38983811 PMCID: PMC11229974 DOI: 10.4239/wjd.v15.i6.1091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 12/22/2023] [Accepted: 04/08/2024] [Indexed: 06/11/2024] Open
Abstract
Disorders in energy homeostasis can lead to various metabolic diseases, particularly obesity. The obesity epidemic has led to an increased incidence of obesity-related nephropathy (ORN), a distinct entity characterized by proteinuria, glomerulomegaly, progressive glomerulosclerosis, and renal function decline. Obesity and its associated renal damage are common in clinical practice, and their incidence is increasing and attracting great attention. There is a great need to identify safe and effective therapeutic modalities, and therapeutics using chemical compounds and natural products are receiving increasing attention. However, the summary is lacking about the specific effects and mechanisms of action of compounds in the treatment of ORN. In this review, we summarize the important clinical features and compound treatment strategies for obesity and obesity-induced kidney injury. We also summarize the pathologic and clinical features of ORN as well as its pathogenesis and potential therapeutics targeting renal inflammation, oxidative stress, insulin resistance, fibrosis, kidney lipid accumulation, and dysregulated autophagy. In addition, detailed information on natural and synthetic compounds used for the treatment of obesity-related kidney disease is summarized. The synthesis of detailed information aims to contribute to a deeper understanding of the clinical treatment modalities for obesity-related kidney diseases, fostering the anticipation of novel insights in this domain.
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Affiliation(s)
- Tuo-Hua Mao
- Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Han-Qi Huang
- Department of Endocrinology, Hubei No. 3 People’s Hospital of Jianghan University, Wuhan 430033, Hubei Province, China
| | - Chuan-Hai Zhang
- Department of Physiology, UT Southwestern Medical Center, Dallas, TX 75390, United States
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14
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Fabunmi OA, Dludla PV, Nkambule BB. High-dose oral contraceptives induce hyperinsulinemia without altering immune activation in diet-induced obesity which persists even following a dietary low-fat diet intervention. J Reprod Immunol 2024; 163:104234. [PMID: 38479054 DOI: 10.1016/j.jri.2024.104234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 02/24/2024] [Accepted: 03/07/2024] [Indexed: 06/03/2024]
Abstract
Combined oral contraceptives (COCs) are known to cause weight gain and alter metabolic and immunological pathways. However, modifications in arterial or venous thrombotic risk profiles of women of reproductive ages on COC remain unclear. The study aimed at assessing the impact of COC on immune activation in diet-induced obesity. We further established whether the dietary intervention of switching from a high-fat diet (HFD) to a low-fat diet (LFD) attenuates immunological responses. Twenty (n=20) five-week-old female Sprague Dawley rats were randomly divided into two diet groups of HFD (n=15) and LFD (n=5) and were monitored for eight weeks. After eight weeks, animals in the HFD group switched diets to LFD and were randomly assigned to receive high-dose COC (HCOC) or low-dose COC (LCOC) for six weeks. Animals on HFD significantly gained weight and had a higher lee index when compared to the LFD group (p < 0.05). Moreover, the triglyceride-glucose index, insulin, and other metabolic parameters also increased in the HFD group compared to the LFD group (p < 0.001). Consistently, the levels of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α), were elevated in the HFD group when compared to the LFD group (p < 0.05). Upon switching from a high-fat to a low-fat diet, insulin levels persistently increased in animals receiving HCOC treatment compared to the LFD and HFD/LFD groups (p < 0.05). Thus, in a rat model of HFD-feeding, short-term HCOC treatment induces long-term metabolic dysregulation, which persists despite dietary intervention. However, further studies are recommended to confirm these findings.
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Affiliation(s)
- Oyesanmi A Fabunmi
- School of Laboratory Medicine and Medical Sciences (SLMMS), College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa; Health-awareness, Exercise and Cardio-immunologic Research Unit (HECIRU), Department of Physiology, College of Medicine, Ekiti State University, Ado-Ekiti 5363, Nigeria.
| | - Phiwayinkosi V Dludla
- Cochrane South Africa, South African Medical Research Council, Tygerberg 7505, South Africa; Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3880, South Africa
| | - Bongani B Nkambule
- School of Laboratory Medicine and Medical Sciences (SLMMS), College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa.
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15
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Tang LJ, Sun DQ, Song SJ, Yip TCF, Wong GLH, Zhu PW, Chen SD, Karsdal M, Leeming DJ, Jiang P, Wang C, Chen Q, Byrne CD, Targher G, Eslam M, George J, Wong VWS, Zheng MH. Serum PRO-C3 is useful for risk prediction and fibrosis assessment in MAFLD with chronic kidney disease in an Asian cohort. Liver Int 2024; 44:1129-1141. [PMID: 38426611 DOI: 10.1111/liv.15878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 01/23/2024] [Accepted: 02/09/2024] [Indexed: 03/02/2024]
Abstract
BACKGROUND Metabolic dysfunction-associated fatty liver disease (MAFLD) is an emerging risk factor for chronic kidney disease (CKD). N-terminal propeptide of collagen type 3 (PRO-C3) is a biomarker of advanced fibrosis in MAFLD and PRO-C3 may be involved in renal fibrosis. We aimed to use PRO-C3 measurements to generate a new algorithmic score to test the prediction of MAFLD with chronic kidney disease (MAFLD-CKD). METHODS A derivation and independent validation cohort of 750 and 129 Asian patients with biopsy-confirmed MAFLD were included. Serum PRO-C3 concentration was measured and regression analyses were performed to examine associations with MAFLD-CKD. A derivative algorithm for MAFLD-CKD risk prediction was evaluated with receiver operator characteristic (ROC) curve analysis. RESULTS The study included two Asian cohorts (n = 180 with MAFLD-CKD; mean-eGFR: 94.93 mL/min/1.73 m2; median-urinary albumin-to-creatinine ratio: 6.58 mg/mmol). PRO-C3 was associated with the severity of MAFLD-CKD and independently associated with MAFLD-CKD (adjusted odds ratio = 1.16, 95% confidence interval [CI]: 1.08-1.23, p < .001). A new non-invasive score (termed PERIOD) including PRO-C3 efficiently predicted MAFLD-CKD (AUROC = .842, 95% CI: .805-.875). Accuracy, specificity and negative predictive values were 80.2%, 85.1% and 88.4%, respectively. In the validation cohort, the PERIOD score had good diagnostic performance (AUROC = .807, 95% CI: .691-.893) with similar results in all patient subgroups. In the MAFLD-CKD subgroup, the accuracy for identifying advanced fibrosis was further improved by combining the PRO-C3-based ADAPT with the Agile 3+ scores (AUROC = .90, 95% CI: .836-.964). CONCLUSIONS The PERIOD score is helpful for accurately predicting the risk of MAFLD-CKD. PRO-C3 can also be used to assess liver fibrosis in people with MAFLD-CKD.
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Affiliation(s)
- Liang-Jie Tang
- MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Cancer Center, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China
| | - Dan-Qin Sun
- Department of Nephrology, Jiangnan University Medical Center, Wuxi, China
- Affiliated Wuxi Clinical College of Nantong University, Wuxi, China
| | - Sherlot Juan Song
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Terry Cheuk-Fung Yip
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Pei-Wu Zhu
- Department of Laboratory Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Sui-Dan Chen
- Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Morten Karsdal
- Nordic Bioscience Biomarkers and Research A/S, Herlev, Denmark
| | | | - Pei Jiang
- Fosun Diagnostics (Shanghai) Co., Ltd, Shanghai, China
| | - Cong Wang
- Fosun Diagnostics (Shanghai) Co., Ltd, Shanghai, China
| | - Qiang Chen
- Cancer Center, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China
- MOE Frontier Science Centre for Precision Oncology, University of Macau, Taipa, Macau SAR, China
| | - Christopher D Byrne
- Southampton National Institute for Health and Care Research, Biomedical Research Centre, University of Southampton and University Hospital Southampton, Southampton, UK
| | - Giovanni Targher
- Department of Medicine, University of Verona, Verona, Italy
- IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Italy
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, Westmead, New South Wales, Australia
- University of Sydney, Sydney, New South Wales, Australia
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, Westmead, New South Wales, Australia
- University of Sydney, Sydney, New South Wales, Australia
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Institute of Hepatology, Wenzhou Medical University, Wenzhou, China
- Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
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16
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Wu JH, Lin KJ, Hsu YH, Chiang YJ, Chu SH, Lin CT, Pan PY, Chen SY, Wang JY, Wang HH. Festivity: The Effects of Traditional Holidays on the Graft Function Among Stable Kidney Recipients. Transplant Proc 2024; 56:546-549. [PMID: 38523012 DOI: 10.1016/j.transproceed.2024.02.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 02/21/2024] [Accepted: 02/29/2024] [Indexed: 03/26/2024]
Abstract
PURPOSE We observed transient elevations in creatinine levels among kidney recipients after three traditional holidays in Taiwan. This retrospective cohort study aimed to compare the changes in eGFR levels after Chinese New Year, Dragon Boat Festival, and Mid-Autumn Festival, all of which are associated with high-calorie and high-fat diets. MATERIALS AND METHODS We conducted a retrospective analysis of 364 kidney recipients with stable graft function who were following at Chang Gung Memorial Hospital Linkou from 2018 to 2020. The graft function before and after the festival was determined by calculating the eGFR level using the serum creatinine measured during clinic visits prior to and following the festival. The patients were then categorized into subgroups based on their sex, BMI, and co-morbidities. The eGFR levels before and after the festival were evaluated and compared within these subgroups. RESULTS A total of 301 kidney recipients have been finally included in this retrospective cohort study. The analysis showed a significant decrease in overall eGFR levels after Chinese New Year (from 56.92 ± 29.70 to 55.14 ± 24.79, P = .006), Mid-Autumn Festival (from 54.03 ± 24.61 to 53.35 ± 24.33, P = .008), and Dragon Boat Festival only in 2020 (from 50.98 ± 24.35 to 49.99 ± 23.45, P = .018). The analysis of subgroups suggested a tendency of renal function decline after all 3 traditional holidays in patient groups with DM or hypertension or nonoverweight status. CONCLUSION In this study, we observed a significant decline in renal function among kidney recipients following traditional holidays in Taiwan, particularly among recipients with hypertension or diabetes mellitus or those who were not overweight.
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Affiliation(s)
- Jen-Hsuan Wu
- Department of Urology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Kuo-Jen Lin
- Department of Urology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ying-Hao Hsu
- Department of Urology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Yang-Jen Chiang
- Department of Urology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan; Chang Gung Transplant Institute, Taoyuan, Taiwan
| | - Sheng-Hsien Chu
- Department of Urology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan; Chang Gung Transplant Institute, Taoyuan, Taiwan
| | - Chih-Te Lin
- Department of Urology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan; Chang Gung Transplant Institute, Taoyuan, Taiwan
| | - Pai-Yen Pan
- Department of Urology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; Chang Gung Transplant Institute, Taoyuan, Taiwan
| | - Sy-Yuan Chen
- Department of Urology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; Chang Gung Transplant Institute, Taoyuan, Taiwan
| | | | - Hsu-Han Wang
- Department of Urology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan; Chang Gung Transplant Institute, Taoyuan, Taiwan.
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17
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U-Din M, Ahmed BA, Syed SA, Ong FJ, Oreskovich SM, Gunn E, Surette MG, Punthakee Z, Steinberg GR, Morrison KM. Characteristics of Abdominal Visceral Adipose Tissue, Metabolic Health and the Gut Microbiome in Adults. J Clin Endocrinol Metab 2024; 109:680-690. [PMID: 37837606 DOI: 10.1210/clinem/dgad604] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 08/30/2023] [Accepted: 10/12/2023] [Indexed: 10/16/2023]
Abstract
CONTEXT Compared with the relatively benign effects of increased subcutaneous adipose tissue (SAT), increased visceral adipose tissue (VAT) volume is a causal risk factor for hypertension, hyperlipidemia, type 2 diabetes, and cardiovascular disease. In rodents, increased VAT volume and triglyceride density and ectopic lipid accumulation in kidneys and liver have been induced by alterations in the gut microbiome. However, few studies have characterized these relationships in humans. OBJECTIVE To evaluate the tissue triglyceride content of VAT and SAT, liver, kidneys, and pancreas in male and female adults and assess associations with markers of glucose tolerance, serum insulin, and lipids and characteristics of the gut microbiome. METHODS Cross-sectional observational study of healthy human adults (n = 60) at a clinical research center. Body mass index (BMI), body composition, and oral glucose tolerance were assessed. Microbiome analysis was conducted on stool samples using 16S rRNA v3 amplicon sequencing. The triglyceride content of VAT, SAT, liver, kidney and pancreas were determined by assessing proton density fat fraction (PDFF) with magnetic resonance imaging (MRI). RESULTS Higher VAT PDFF and the ratio of VAT to SAT PDFF were related to higher BMI, HbA1c, HOMA-IR, non-high-density lipoprotein cholesterol, plasma triglycerides, low-density lipoprotein (LDL) cholesterol, and lower high-density lipoprotein (HDL) cholesterol. A higher VAT PDFF and VAT to SAT PDFF ratio were associated with lower alpha diversity and altered beta diversity of the gut microbiome. Differences in VAT were associated with higher relative abundance of the phylum Firmicutes, lower relative abundance of the phylum Bacteroidetes, and enrichment of the bacterial genera Dorea, Streptococcus, and Solobacterium. CONCLUSION VAT PDFF measured with MRI is related to impaired glucose homeostasis, dyslipidemia, and differences in the gut microbiome, independently of the total body fat percentage.
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Affiliation(s)
- Mueez U-Din
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON L8S 4L8, Canada
- Turku PET Centre, Turku University Hospital, Turku 20520, Finland
| | - Basma A Ahmed
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON L8S 4L8, Canada
- Department of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada
- Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada
| | - Saad A Syed
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON L8S 4L8, Canada
- Department of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON L8S 4L8, Canada
| | - Frank J Ong
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON L8S 4L8, Canada
| | - Stephan M Oreskovich
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON L8S 4L8, Canada
| | - Elizabeth Gunn
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON L8S 4L8, Canada
| | - Michael G Surette
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON L8S 4L8, Canada
- Department of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada
- Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON L8S 4L8, Canada
| | - Zubin Punthakee
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON L8S 4L8, Canada
- Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada
| | - Gregory R Steinberg
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON L8S 4L8, Canada
- Department of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, ON L8S 4L8, Canada
- Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada
| | - Katherine M Morrison
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON L8S 4L8, Canada
- Department of Paediatrics, McMaster University, Hamilton, ON L8S 4L8, Canada
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18
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Almoraie NM, Shatwan IM. The Potential Effects of Dietary Antioxidants in Obesity: A Comprehensive Review of the Literature. Healthcare (Basel) 2024; 12:416. [PMID: 38391792 PMCID: PMC10887832 DOI: 10.3390/healthcare12040416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 01/19/2024] [Accepted: 02/03/2024] [Indexed: 02/24/2024] Open
Abstract
Obesity has become a global health concern, with its prevalence steadily increasing in recent decades. It is associated with numerous health complications, including cardiovascular diseases, diabetes, and certain types of cancer. The aetiology of obesity is multifactorial, involving genetic, environmental, and lifestyle factors. In recent years, oxidative stress has emerged as a potential contributor to obesity and its related metabolic disorders. Dietary antioxidants, which can counteract oxidative stress, have gained significant attention for their potential role in preventing and managing obesity. This comprehensive review aims to explore the impact of dietary antioxidants on obesity and its associated metabolic dysregulations, discussing the underlying mechanisms and highlighting the potential therapeutic implications.
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Affiliation(s)
- Noha M Almoraie
- Food and Nutrition Department, Faculty of Human Sciences and Design, King Abdulaziz University, Building 43, Room 233, Level 2, Jeddah 3270, Saudi Arabia
| | - Israa M Shatwan
- Food and Nutrition Department, Faculty of Human Sciences and Design, King Abdulaziz University, Building 43, Room 233, Level 2, Jeddah 3270, Saudi Arabia
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Liang J, He Y, Huang C, Ji F, Zhou X, Yin Y. The Regulation of Selenoproteins in Diabetes: A New Way to Treat Diabetes. Curr Pharm Des 2024; 30:1541-1547. [PMID: 38706350 DOI: 10.2174/0113816128302667240422110226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 03/31/2024] [Indexed: 05/07/2024]
Abstract
Selenium is an essential micronutrient required for the synthesis and function of selenoproteins, most of which are enzymes involved in maintaining oxidative balance in the body. Diabetes is a group of metabolic disorders characterized by high blood glucose levels over a prolonged period of time. There are three main types of diabetes: type 1, type 2, and gestational diabetes. This review summarizes recent advances in the field of diabetes research with an emphasis on the roles of selenoproteins on metabolic disturbance in diabetes. We also discuss the interaction between selenoproteins and glucose and lipid metabolism to provide new insights into the prevention and treatment of diabetes.
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Affiliation(s)
- Jing Liang
- Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha 410125, China
- College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yiwen He
- Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha 410125, China
- Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, College of Life Sciences, Hunan Normal University, Changsha 410081, China
| | - Chunxia Huang
- School of Stomatology, Changsha Medical University, Changsha 410219, China
| | - Fengjie Ji
- Tropical Crops Genetic Resources Institute, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China
| | - Xihong Zhou
- Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha 410125, China
- College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Yulong Yin
- Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha 410125, China
- College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
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20
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Sawie HG, Khadrawy YA, El-Gizawy MM, Mourad HH, Omara EA, Hosny EN. Effect of alpha-lipoic acid and caffeine-loaded chitosan nanoparticles on obesity and its complications in liver and kidney in rats. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2023; 396:3017-3031. [PMID: 37306714 PMCID: PMC10567965 DOI: 10.1007/s00210-023-02507-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 04/19/2023] [Indexed: 06/13/2023]
Abstract
The present work investigated the effect of α-lipoic acid (ALA) and caffeine-loaded chitosan nanoparticles (CAF-CS NPs) on obesity and its hepatic and renal complications in rats. Rats were divided into control, rat model of obesity induced by high fat diet (HFD), and obese rats treated with ALA and/or CAF-CS NPs. At the end of the experiment, the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) and the levels of urea, creatinine, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were determined in the sera of animals. In addition, malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione (GSH) were measured in hepatic and renal tissues. Renal Na+, K+-ATPase was assessed. The histopathological changes were examined in the hepatic and renal tissues. Obese rats showed a significant increase in AST, ALT, ALP, urea, and creatinine. This was associated with a significant increase in IL-1β, TNF-α, MDA, and NO. A significant decrease in hepatic and renal GSH and renal Na+, K+-ATPase activity was recorded in obese rats. Obese rats also showed histopathological alterations in hepatic and renal tissues. Treatment with ALA and/or CAF-CS NPs reduced the weight of obese rats and ameliorated almost all the hepatic and renal biochemical and histopathological changes induced in obese rats. In conclusion, the present findings indicate that ALA and/or CAF-CS NPs offered an effective therapy against obesity induced by HFD and its hepatic and renal complications. The therapeutic effect of ALA and CAF-CS NPs could be mediated through their antioxidant and anti-inflammatory properties.
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Affiliation(s)
- Hussein G Sawie
- Medical Physiology Department, Medical Research and Clinical Studies Institute, National Research Centre, El-Behouth St, Giza, Egypt
| | - Yasser A Khadrawy
- Medical Physiology Department, Medical Research and Clinical Studies Institute, National Research Centre, El-Behouth St, Giza, Egypt
| | - Mayada M El-Gizawy
- Medical Physiology Department, Medical Research and Clinical Studies Institute, National Research Centre, El-Behouth St, Giza, Egypt
| | - Hagar H Mourad
- Medical Physiology Department, Medical Research and Clinical Studies Institute, National Research Centre, El-Behouth St, Giza, Egypt
| | - Enayat A Omara
- Pathology Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt
| | - Eman N Hosny
- Medical Physiology Department, Medical Research and Clinical Studies Institute, National Research Centre, El-Behouth St, Giza, Egypt.
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21
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Cai Y, Zhang S, Chen L, Fu Y. Integrated multi-omics and machine learning approach reveals lipid metabolic biomarkers and signaling in age-related meibomian gland dysfunction. Comput Struct Biotechnol J 2023; 21:4215-4227. [PMID: 37675286 PMCID: PMC10480060 DOI: 10.1016/j.csbj.2023.08.026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Revised: 08/26/2023] [Accepted: 08/26/2023] [Indexed: 09/08/2023] Open
Abstract
Meibomian gland dysfunction (MGD) is a prevalent inflammatory disorder of the ocular surface that significantly impacts patients' vision and quality of life. The underlying mechanism of aging and MGD remains largely uncharacterized. The aim of this work is to investigate lipid metabolic alterations in age-related MGD (ARMGD) through integrated proteomics, lipidomics and machine learning (ML) approach. For this purpose, we collected samples of female mouse meibomian glands (MGs) dissected from eyelids at age two months (n = 9) and two years (n = 9) for proteomic and lipidomic profilings using the liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. To further identify ARMGD-related lipid biomarkers, ML model was established using the least absolute shrinkage and selection operator (LASSO) algorithm. For proteomic profiling, 375 differentially expressed proteins were detected. Functional analyses indicated the leading role of cholesterol biosynthesis in the aging process of MGs. Several proteins were proposed as potential biomarkers, including lanosterol synthase (Lss), 24-dehydrocholesterol reductase (Dhcr24), and farnesyl diphosphate farnesyl transferase 1 (Fdft1). Concomitantly, lipidomic analysis unveiled 47 lipid species that were differentially expressed and clustered into four classes. The most notable age-related alterations involved a decline in cholesteryl esters (ChE) levels and an increase in triradylglycerols (TG) levels, accompanied by significant differences in their lipid unsaturation patterns. Through ML construction, it was confirmed that ChE(26:0), ChE(26:1), and ChE(30:1) represent the most promising diagnostic molecules. The present study identified essential proteins, lipids, and signaling pathways in age-related MGD (ARMGD), providing a reference landscape to facilitate novel strategies for the disease transformation.
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Affiliation(s)
- Yuchen Cai
- Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Siyi Zhang
- Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Liangbo Chen
- Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Yao Fu
- Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
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22
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Kostyukevich Y, Stekolshikova E, Levashova A, Kovalenko A, Vishnevskaya A, Bashilov A, Kireev A, Tupertsev B, Rumiantseva L, Khaitovich P, Osipenko S, Nikolaev E. Untargeted Lipidomics after D 2O Administration Reveals the Turnover Rate of Individual Lipids in Various Organs of Living Organisms. Int J Mol Sci 2023; 24:11725. [PMID: 37511483 PMCID: PMC10380497 DOI: 10.3390/ijms241411725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 07/13/2023] [Accepted: 07/19/2023] [Indexed: 07/30/2023] Open
Abstract
The administration of low doses of D2O to living organisms was used for decades for the investigation of metabolic pathways and for the measurement of the turnover rate for specific compounds. Usually, the investigation of the deuterium uptake in lipids is performed by measuring the deuteration level of the palmitic acid residue using GC-MS instruments, and to our knowledge, the application of the modern untargeted LC-MS/MS lipidomics approaches was only reported a few times. Here, we investigated the deuterium uptake for >500 lipids for 13 organs and body liquids of mice (brain, lung, heart, liver, kidney, spleen, plasma, urine, etc.) after 4 days of 100% D2O administration. The maximum deuteration level was observed in the liver, plasma, and lung, while in the brain and heart, the deuteration level was lower. Using MS/MS, we demonstrated the incorporation of deuterium in palmitic and stearic fragments in lipids (PC, PE, TAG, PG, etc.) but not in the corresponding free forms. Our results were analyzed based on the metabolic pathways of lipids.
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Affiliation(s)
- Yury Kostyukevich
- Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, Bld. 1, 121205 Moscow, Russia
| | - Elena Stekolshikova
- Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, Bld. 1, 121205 Moscow, Russia
| | - Anna Levashova
- Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, Bld. 1, 121205 Moscow, Russia
- Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency, Krasnogorsky District, Village Light Mountains, Bld. 1, 143442 Moscow, Russia
| | - Anna Kovalenko
- Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, Bld. 1, 121205 Moscow, Russia
| | - Anna Vishnevskaya
- Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, Bld. 1, 121205 Moscow, Russia
| | - Anton Bashilov
- Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, Bld. 1, 121205 Moscow, Russia
| | - Albert Kireev
- Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, Bld. 1, 121205 Moscow, Russia
| | - Boris Tupertsev
- Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, Bld. 1, 121205 Moscow, Russia
| | - Lidiia Rumiantseva
- Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, Bld. 1, 121205 Moscow, Russia
| | - Philipp Khaitovich
- Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, Bld. 1, 121205 Moscow, Russia
| | - Sergey Osipenko
- Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, Bld. 1, 121205 Moscow, Russia
| | - Eugene Nikolaev
- Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, Bld. 1, 121205 Moscow, Russia
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23
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Sun DQ, Targher G, Byrne CD, Wheeler DC, Wong VWS, Fan JG, Tilg H, Yuan WJ, Wanner C, Gao X, Long MT, Kanbay M, Nguyen MH, Navaneethan SD, Yilmaz Y, Huang Y, Gani RA, Marzuillo P, Boursier J, Zhang H, Jung CY, Chai J, Valenti L, Papatheodoridis G, Musso G, Wong YJ, El-Kassas M, Méndez-Sánchez N, Sookoian S, Pavlides M, Duseja A, Holleboom AG, Shi J, Chan WK, Fouad Y, Yang J, Treeprasertsuk S, Cortez-Pinto H, Hamaguchi M, Romero-Gomez M, Al Mahtab M, Ocama P, Nakajima A, Dai C, Eslam M, Wei L, George J, Zheng MH. An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease. Hepatobiliary Surg Nutr 2023; 12:386-403. [PMID: 37351121 PMCID: PMC10282675 DOI: 10.21037/hbsn-22-421] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 02/01/2023] [Indexed: 08/27/2023]
Abstract
BACKGROUND With the rising global prevalence of fatty liver disease related to metabolic dysfunction, the association of this common liver condition with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the term non-alcoholic fatty liver disease (NAFLD). The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD. However, to date, there is no appropriate guidance on CKD in individuals with MAFLD. Furthermore, there has been little attention paid to the link between MAFLD and CKD in the Nephrology community. METHODS AND RESULTS Using a Delphi-based approach, a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD. CONCLUSIONS This Delphi-based consensus statement provided guidance on the epidemiology, mechanisms, management and treatment of MAFLD and CKD, as well as the relationship between the severity of MAFLD and risk of CKD, which establish a framework for the early prevention and management of these two common and interconnected diseases.
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Affiliation(s)
- Dan-Qin Sun
- Department of Nephrology, Jiangnan University Medical Center, Wuxi, China
- Affiliated Wuxi Clinical College of Nantong University, Wuxi, China
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
| | - Christopher D. Byrne
- Southampton National Institute for Health and Care Research Biomedical Research Centre, University Hospital Southampton, and Southampton General Hospital, University of Southampton, Southampton, UK
| | - David C. Wheeler
- Department of Renal Medicine, University College London, London, UK
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China
| | - Jian-Gao Fan
- Center for Fatty Liver, Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria
| | - Wei-Jie Yuan
- Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Christoph Wanner
- Division of Nephrology, Department of Medicine, Würzburg University Clinic, Würzburg, Germany
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Michelle T. Long
- Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Mehmet Kanbay
- Division of Nephrology, Department of Medicine (M.K.), Koc University School of Medicine, Istanbul, Turkey
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA
- Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA, USA
| | - Sankar D. Navaneethan
- Section of Nephrology and Institute of Clinical and Translational Research, Baylor College of Medicine, and Michael E. DeBakey VA Medical Center, Houston, TX, USA
| | - Yusuf Yilmaz
- Department of Gastroenterology, School of Medicine, Marmara University, Istanbul, Turkey
- Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey
| | - Yuli Huang
- Department of Cardiology, Shunde Hospital, Southern Medical University, Foshan, China
| | - Rino A. Gani
- Division of Hepatobiliary, Department of Internal Medicine, Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Jakarta, Indonesia
| | - Pierluigi Marzuillo
- Department of Woman, Child and of General and Specialized Surgery, Università della Campania “Luigi Vanvitelli”, Napoli, Italy
| | - Jérôme Boursier
- HIFIH Laboratory, UPRES EA3859, Angers University, Angers, France
- Hepato-Gastroenterology and Digestive Oncology Department, Angers University Hospital, Angers, France
| | - Huijie Zhang
- Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Chan-Young Jung
- Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Republic of Korea
| | - Jin Chai
- Cholestatic Liver Diseases Center, Department of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Luca Valenti
- Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milano, Università degli Studi di Milano, Milan, Italy
| | - George Papatheodoridis
- Department of Gastroenterology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Giovanni Musso
- Emergency and Intensive Care Medicine, HUMANITAS Gradenigo Hospital;
| | - Yu-Jun Wong
- Department of Gastroenterology & Hepatology, Changi General Hospital, Singhealth, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
| | - Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
| | | | - Silvia Sookoian
- Clinical and Molecular Hepatology, Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
| | - Michael Pavlides
- Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Adriaan G. Holleboom
- Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Junping Shi
- Department of Hepatology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China
| | - Wah-Kheong Chan
- Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Yasser Fouad
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Minia University, Minya, Egypt
| | - Junwei Yang
- Center for Kidney Disease, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | | | - Helena Cortez-Pinto
- Clínica Universitária de Gastrenterologia, Laboratório de Nutrição, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
| | - Masahide Hamaguchi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Manuel Romero-Gomez
- UCM Digestive Diseases, University Hospital Virgen del Rocio, Institute of Biomedicine of Seville (CSIC/HUVR/US), Ciberehd, University of Seville, Sevilla, Spain
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Ponsiano Ocama
- Department of Medicine, Makerere University of College of Health Sciences, Kampala, Uganda
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Chunsun Dai
- Center for Kidney Disease, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, China
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Lai Wei
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
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24
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Pereira PR, Pereira J, Braga PC, Pereira SS, Nora M, Guimarães M, Monteiro MP, Rodrigues A. Renal Dysfunction Phenotypes in Patients Undergoing Obesity Surgery. Biomolecules 2023; 13:biom13050790. [PMID: 37238660 DOI: 10.3390/biom13050790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 04/30/2023] [Accepted: 05/02/2023] [Indexed: 05/28/2023] Open
Abstract
Obesity surgery candidates are at an increased risk of kidney injury, but pre-operative evaluation usually neglects kidney function assessment. This study aimed to identify renal dysfunction in candidates for bariatric surgery. To reduce the sources of bias, subjects with diabetes, prediabetes under metformin treatment, neoplastic or inflammatory diseases were excluded. Patients' (n = 192) average body mass index was 41.7 ± 5.4 kg/m2. Among these, 51% (n = 94) had creatinine clearance over 140 mL/min, 22.4% (n = 43) had proteinuria over 150 mg/day and 14.6% (n = 28) albuminuria over 30 mg/day. A creatinine clearance higher than 140 mL/min was associated with higher levels of proteinuria and albuminuria. Univariate analysis identified sex, glycated hemoglobin, uric acid, HDL and VLDL cholesterol as being associated with albuminuria, but not with proteinuria. On multivariate analysis, glycated hemoglobin and creatinine clearance as continuous variables were significantly associated with albuminuria. In summary, in our patient population prediabetes, lipid abnormalities and hyperuricemia were associated with albuminuria, but not with proteinuria, suggesting different disease mechanisms might be implicated. Data suggest that in obesity-associated kidney disease, tubulointerstitial injury precedes glomerulopathy. A significant proportion of obesity surgery candidates present clinically relevant albuminuria and proteinuria along with renal hyperfiltration, suggesting that routine pre-operative assessment of these parameters should be considered.
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Affiliation(s)
- Pedro R Pereira
- Department of Nephrology, Centro Hospitalar de Trás-os-Montes e Alto Douro (CHTMAD), 5000-508 Vila Real, Portugal
- UMIB-Unit for Multidisciplinary Research in Biomedicine, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
- ITR-Laboratory of Integrative and Translocation Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal
| | - João Pereira
- UMIB-Unit for Multidisciplinary Research in Biomedicine, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
- ITR-Laboratory of Integrative and Translocation Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal
| | - Patrícia C Braga
- UMIB-Unit for Multidisciplinary Research in Biomedicine, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
- ITR-Laboratory of Integrative and Translocation Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal
| | - Sofia S Pereira
- UMIB-Unit for Multidisciplinary Research in Biomedicine, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
- ITR-Laboratory of Integrative and Translocation Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal
| | - Mário Nora
- Department of General Surgery, Hospital São Sebastião, Centro Hospitalar de Entre o Douro e Vouga, Rua Dr. Cândido Pinho, 4050-220 Santa Maria da Feira, Portugal
| | - Marta Guimarães
- UMIB-Unit for Multidisciplinary Research in Biomedicine, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
- ITR-Laboratory of Integrative and Translocation Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal
- Department of General Surgery, Hospital São Sebastião, Centro Hospitalar de Entre o Douro e Vouga, Rua Dr. Cândido Pinho, 4050-220 Santa Maria da Feira, Portugal
| | - Mariana P Monteiro
- UMIB-Unit for Multidisciplinary Research in Biomedicine, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
- ITR-Laboratory of Integrative and Translocation Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal
| | - Anabela Rodrigues
- UMIB-Unit for Multidisciplinary Research in Biomedicine, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
- ITR-Laboratory of Integrative and Translocation Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal
- Department of Nephrology, Centro Hospitalar Universitário de Santo António, 4099-001 Porto, Portugal
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25
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Zhang XL, Zhang M, Lei N, Ouyang WW, Chen HF, Lao BN, Xu YM, Tang F, Fu LZ, Liu XS, Wu YF. An investigation of low-protein diets' qualification rates and an analysis of their short-term effects for patients with CKD stages 3-5: a single-center retrospective cohort study from China. Int Urol Nephrol 2023; 55:1059-1070. [PMID: 36310191 PMCID: PMC10030416 DOI: 10.1007/s11255-022-03390-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 10/15/2022] [Indexed: 03/22/2023]
Abstract
BACKGROUND The feasibility and efficacy of low-protein diets (LPD) treatment in chronic kidney disease (CKD) is controversial. Based on the characteristics of the Chinese diet, we observe the qualification rates and short-term clinical effects of LPD for CKD patients in our center. METHODS This is a retrospective cohort study. CKD stages 3-5 patients who were regularly followed up 5 times (over 2 years) and treated with LPD were included. We collected clinical data to observe the changes in LPD qualification rates and divided patients into LPD and non-LPD group according to the average dietary protein intake (DPI) of 5 follow-up time points and compared the changes in primary and secondary outcome measures between the two groups. RESULTS We analyzed data from 161 eligible CKD stages 3-5 patients. From baseline to the 5th follow-up time point, the LPD qualification rates of all patients were 11.80%, 35.40%, 47.82%, 53.43% and 54.04%, respectively. For primary outcome measures, the urine protein/creatinine ratio (UPCR) decreased more in the LPD group than in the non-LPD group [Median (interquartile range, IQR) of the difference between the 5th follow-up time point and baseline: 0.19 (- 0.01-0.73) vs. 0.10 (- 0.08-0.27), P < 0.001]. We constructed three classes of mixed linear models (model I, II, III). The UPCR slopes were all negative in the LPD group and positive in the non-LPD group (P < 0.001). Meanwhile, in model I, the estimate glomerular filtration rate(eGFR) decline slope in the LPD group was lower than that in the non-LPD group [slope (standard error): - 1.32 (0.37) vs. - 2.35 (0.33), P = 0.036]. For secondary outcome measures, body mass index (BMI) triglycerides (TG), body weight, and fat free mass (FFM) showed stable statistical differences in the comparison of LPD and non-LPD groups, with greater declines in the former. CONCLUSION The results of this study suggest that LPD treatment can reduce UPCR in patients with CKD stages 3-5, and may also delay the decline in eGFR. Meanwhile, it also reduces BMI, TG, body weight, and FFM, thus the need to prevent malnutrition in clinical implementation.
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Affiliation(s)
- Xian-Long Zhang
- Renal Division, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong, China
| | - Min Zhang
- The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Nuo Lei
- The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Wen-Wei Ouyang
- Key Unit of Methodology in Clinical Research, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
| | - Hui-Fen Chen
- The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Bei-Ni Lao
- The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yan-Min Xu
- The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Fang Tang
- Chronic Disease Management Outpatient, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
| | - Li-Zhe Fu
- Chronic Disease Management Outpatient, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
| | - Xu-Sheng Liu
- Renal Division, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong, China
| | - Yi-Fan Wu
- Renal Division, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong, China.
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Serrano E, Shenoy P, Martinez Cantarin MP. Adipose tissue metabolic changes in chronic kidney disease. IMMUNOMETABOLISM (COBHAM (SURREY, ENGLAND)) 2023; 5:e00023. [PMID: 37128293 PMCID: PMC10144329 DOI: 10.1097/in9.0000000000000023] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 04/04/2023] [Indexed: 05/03/2023]
Abstract
Adipose tissue is a complex organ whose functions go beyond being an energy reservoir to sustain proper body energy homeostasis. Functioning as an endocrine organ, the adipose tissue has an active role in the body's metabolic balance regulation through several secreted factors generally termed as adipokines. Thus, adipose tissue dysregulation in chronic kidney disease (CKD) can have a deep impact in the pathophysiology of diseases associated with metabolic dysregulation including metabolic syndrome, insulin resistance (IR), atherosclerosis, and even cachexia. CKD is a progressive disorder linked to increased morbidity and mortality. Despite being characterized by renal function loss, CKD is accompanied by metabolic disturbances such as dyslipidemia, protein energy wasting, chronic low-grade inflammation, IR, and lipid redistribution. Thus far, the mechanisms by which these changes occur and the role of adipose tissue in CKD development and progression are unclear. Further understanding of how these factors develop could have implications for the management of CKD by helping identify pharmacological targets to improve CKD outcomes.
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Affiliation(s)
- Eurico Serrano
- Division of Nephrology, Department of Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA
| | - Prashamsa Shenoy
- Division of Nephrology, Department of Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA
| | - Maria Paula Martinez Cantarin
- Division of Nephrology, Department of Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA
- *Correspondence: Maria Paula Martinez Cantarin, E-mail:
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Advanced Oxidation Protein Products Contribute to Chronic-Kidney-Disease-Induced Adipose Inflammation through Macrophage Activation. Toxins (Basel) 2023; 15:toxins15030179. [PMID: 36977070 PMCID: PMC10059001 DOI: 10.3390/toxins15030179] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 02/22/2023] [Accepted: 02/24/2023] [Indexed: 03/03/2023] Open
Abstract
Fat atrophy and adipose tissue inflammation can cause the pathogenesis of metabolic symptoms in chronic kidney disease (CKD). During CKD, the serum levels of advanced oxidation protein products (AOPPs) are elevated. However, the relationship between fat atrophy/adipose tissue inflammation and AOPPs has remained unknown. The purpose of this study was to investigate the involvement of AOPPs, which are known as uremic toxins, in adipose tissue inflammation and to establish the underlying molecular mechanism. In vitro studies involved co-culturing mouse-derived adipocytes (differentiated 3T3-L1) and macrophages (RAW264.7). In vivo studies were performed using adenine-induced CKD mice and AOPP-overloaded mice. Fat atrophy, macrophage infiltration and increased AOPP activity in adipose tissue were identified in adenine-induced CKD mice. AOPPs induced MCP-1 expression in differentiated 3T3-L1 adipocytes via ROS production. However, AOPP-induced ROS production was suppressed by the presence of NADPH oxidase inhibitors and the scavengers of mitochondria-derived ROS. A co-culturing system showed AOPPs induced macrophage migration to adipocytes. AOPPs also up-regulated TNF-α expression by polarizing macrophages to an M1-type polarity, and then induced macrophage-mediated adipose inflammation. In vitro data was supported by experiments using AOPP-overloaded mice. AOPPs contribute to macrophage-mediated adipose inflammation and constitute a potential new therapeutic target for adipose inflammation associated with CKD.
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Egg Yolk Fat Deposition Is Regulated by Diacylglycerol and Ceramide Enriched by Adipocytokine Signaling Pathway in Laying Hens. Animals (Basel) 2023; 13:ani13040607. [PMID: 36830395 PMCID: PMC9951658 DOI: 10.3390/ani13040607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 01/19/2023] [Accepted: 01/30/2023] [Indexed: 02/11/2023] Open
Abstract
The mechanism which regulates differential fat deposition in egg yolk from the indigenous breeds and commercial laying hens is still unclear. In this research, Chinese indigenous Huainan Partridge chickens and Nongda III commercial laying hens were used for egg collection and liver sampling. The weight of eggs and yolk were recorded. Yolk fatty acids were determined by gas chromatography-mass spectrometry. Lipid metabolites in the liver were detected by liquid chromatography-mass spectrometry. Yolk weight, yolk ratio and yolk fat ratio exhibited higher in the Huainan Partridge chicken than that of the Nongda III. Compared to the Nongda III, the content of total saturated fatty acid was lower, while the unsaturated fatty acid was higher in the yolk of the Huainan Partridge chicken. Metabolites of phosphatidylinositol and phosphatidylserine from glycerolphospholipids, and metabolites of diacylglycerol from glycerolipids showed higher enrichment in the Huainan Partridge chicken than that of the Nongda III, which promoted the activation of the adipocytokine signaling pathway. However, metabolites of phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine and lysophosphatidylcholine from glycerol phospholipids, and metabolites of triacylglycerol from glycerolipids showed lower enrichment in the Huainan Partridge chicken than that of the Nongda III. The high level of yolk fat deposition in the Huainan Partridge chicken is regulated by the activation of the adipocytokine signaling pathway which can promote the accumulation of diacylglycerol and ceramide in the liver.
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Wang K, Zhao Y, Xu L, Liao X, Xu Z. Health outcomes of 100% orange juice and orange flavored beverage: A comparative analysis of gut microbiota and metabolomics in rats. Curr Res Food Sci 2023; 6:100454. [PMID: 36815996 PMCID: PMC9932342 DOI: 10.1016/j.crfs.2023.100454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 01/08/2023] [Accepted: 02/01/2023] [Indexed: 02/05/2023] Open
Abstract
A high intake of sugar-sweetened fruity beverage (FB) is associated with a higher risk of metabolic syndromes, but the health outcome of 100% fruit juice (FJ) intake remains unclear. We aim to reveal health outcomes of diet intervention (FJ or FB) with system profiling via interaction of gut microbiota and metabolomics in a rat (Rattus norvegicus) model. Firstly, the glucose, sucrose, fructose, and bioactive metabolites of FJ and FB were analyzed, and FJ possessed higher sucrose and flavonoids, while FB showed higher glucose and fructose. Secondly, C0 was set as the control group on Day 0, and a 4-week diet invention was performed to control, FJ-intake, and FB-intake groups with normal saline, FJ, and FB, respectively. The results showed that FJ improved alpha diversity and decreased the Firmicutes/Bacteroidota ratio (F/B ratio) of gut microbiota and prevented insulin resistance. However, FB possessed unchanged microbial diversity and enhanced F/B ratio, causing insulin resistance with renal triglyceride accumulation. In summary, FJ, although naturally containing similar amounts of total free sugars as FB, could be a healthier drink choice.
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Affiliation(s)
- Kewen Wang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China
- Institute of Quality Standard & Testing Technology for Agro-Products, Key Laboratory of Agro-food Safety and Quality, Ministry of Agriculture and Rural Affairs, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - Yang Zhao
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China
| | - Lei Xu
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China
- Institute of Quality Standard & Testing Technology for Agro-Products, Key Laboratory of Agro-food Safety and Quality, Ministry of Agriculture and Rural Affairs, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - Xiaojun Liao
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China
- Corresponding author.
| | - Zhenzhen Xu
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China
- Institute of Quality Standard & Testing Technology for Agro-Products, Key Laboratory of Agro-food Safety and Quality, Ministry of Agriculture and Rural Affairs, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
- Corresponding author. College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China.
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Nephroprotective Effect of Fennel ( Foeniculum vulgare) Seeds and Their Sprouts on CCl 4-Induced Nephrotoxicity and Oxidative Stress in Rats. Antioxidants (Basel) 2023; 12:antiox12020325. [PMID: 36829884 PMCID: PMC9952328 DOI: 10.3390/antiox12020325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 01/22/2023] [Accepted: 01/26/2023] [Indexed: 02/01/2023] Open
Abstract
Functional and nutritional characteristics of seed sprouts and their association with oxidative stress-related disorders have recently become a focus of scientific investigations. The biological activities of fennel seeds (FS) and fennel seed sprouts (FSS) were investigated in vitro and in vivo. The total phenolic content (TPC), total flavonoids (TF), total flavonols (TFF), and antioxidant activity (AOA) of FS and FSS were examined. HPLC and GC-MS analyses for FS and FSS were carried out. Consequently, the nephroprotective and antioxidative stress potential of FS and FSS extracts at 300 and 600 mg kg-1 on CCl4-induced nephrotoxicity and oxidative stress in rats was investigated. In this context, kidney relative weight, blood glucose level (BGL), lipid profile, kidney function (T. protein, albumin, globulin, creatinine, urea, and blood urea nitrogen (BUN)), and oxidative stress biomarkers (GSH, CAT, MDA, and SOD) in the rat's blood as well as the histopathological alteration in kidney tissues were examined. Results indicated that the sprouting process of FS significantly improved TPC, TF, TFL, and AOA in vitro. HPLC identified nineteen compounds of phenolic acids and their derivatives in FS. Thirteen phenolic compounds in FS and FSS were identified, the highest of which was vanillic acid. Six flavonoids were also identified with a predominance of kaempferol. GC-MS indicated that the trans-anethole (1-methoxy-4-[(E)-prop-1-enyl]benzene) component was predominant in FS and FSS, significantly increasing after sprouting. In in vivo examination, administering FS and FSS extracts ameliorated the BGL, triglycerides (TG), total cholesterol (CHO), and their derivative levels compared to CCl4-intoxicated rats. A notable improvement in FS and FSS with 600 mg kg-1 compared to 300 mg kg-1 was observed. A dose of 600 mg FSS kg-1 reduced the TG, CHO, and LDL-C and increased HDL-C levels by 32.04, 24.62, 63.00, and 67.17% compared to G2, respectively. The atherogenic index (AI) was significantly improved with 600 mg kg-1 of FSS extracts. FS and FSS improved kidney function, reduced malondialdehyde (MDA), and restored the activity of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Both FS and FSS extracts attenuated the histopathological alteration in CCl4-treated rats. Interestingly, FSS extract presented better efficiency as a nephroprotection agent than FS extract. In conclusion, FSS can potentially restore oxidative stability and improve kidney function after acute CCl4 kidney injury better than FS. Therefore, FS and FSS extracts might be used for their promising nephroprotective potential and to help prevent diseases related to oxidative stress. Further research on their application in humans is highly recommended.
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Baumgartner C, Krššák M, Vila G, Krebs M, Wolf P. Ectopic lipid metabolism in anterior pituitary dysfunction. Front Endocrinol (Lausanne) 2023; 14:1075776. [PMID: 36860364 PMCID: PMC9968795 DOI: 10.3389/fendo.2023.1075776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Accepted: 02/02/2023] [Indexed: 02/17/2023] Open
Abstract
Over the past decades, adapted lifestyle and dietary habits in industrialized countries have led to a progress of obesity and associated metabolic disorders. Concomitant insulin resistance and derangements in lipid metabolism foster the deposition of excess lipids in organs and tissues with limited capacity of physiologic lipid storage. In organs pivotal for systemic metabolic homeostasis, this ectopic lipid content disturbs metabolic action, thereby promotes the progression of metabolic disease, and inherits a risk for cardiometabolic complications. Pituitary hormone syndromes are commonly associated with metabolic diseases. However, the impact on subcutaneous, visceral, and ectopic fat stores between disorders and their underlying hormonal axes is rather different, and the underlying pathophysiological pathways remain largely unknown. Pituitary disorders might influence ectopic lipid deposition indirectly by modulating lipid metabolism and insulin sensitivity, but also directly by organ specific hormonal effects on energy metabolism. In this review, we aim to I) provide information about the impact of pituitary disorders on ectopic fat stores, II) and to present up-to-date knowledge on potential pathophysiological mechanisms of hormone action in ectopic lipid metabolism.
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Is bariatric surgery improving mitochondrial function in the renal cells of patients with obesity-induced kidney disease? Pharmacol Res 2022; 185:106488. [DOI: 10.1016/j.phrs.2022.106488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/28/2022] [Accepted: 10/03/2022] [Indexed: 11/22/2022]
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Lai W, Shi M, Huang R, Fu P, Ma L. Fatty acid-binding protein 4 in kidney diseases: From mechanisms to clinics. Eur J Pharmacol 2022; 931:175224. [PMID: 35995212 DOI: 10.1016/j.ejphar.2022.175224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Revised: 07/28/2022] [Accepted: 08/16/2022] [Indexed: 11/03/2022]
Abstract
Considerable evidence indicated the relationship between fatty acid-binding protein 4 (FABP4) and kidney diseases. FABP4, a small molecular lipid chaperone, is identified to regulate fatty acid oxidation, inflammation, apoptosis, endoplasmic reticulum stress and macrophage-to-myofibroblast transition in kidney diseases. Many studies have shown that circulating FABP4 level is related to proteinuria, renal function decline, cardiovascular complications of end-stage renal disease and even the prognosis of kidney transplanted patients. Notably, pharmacological or genetic inhibition of FABP4 attenuated renal injury in the various experimental models of kidney diseases, making it promising to develop potential therapeutic strategies targeting FABP4 in kidney diseases. In this study, we updated and reviewed the mechanisms and clinical significance of FABP4 in kidney diseases.
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Affiliation(s)
- Weijing Lai
- Kidney Research Institute, Department of Nephrology, West China Hospital of Sichuan University, Sichuan, Chengdu, 610041, China; Department of Nephrology, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, China
| | - Min Shi
- Kidney Research Institute, Department of Nephrology, West China Hospital of Sichuan University, Sichuan, Chengdu, 610041, China
| | - Rongshuang Huang
- Kidney Research Institute, Department of Nephrology, West China Hospital of Sichuan University, Sichuan, Chengdu, 610041, China
| | - Ping Fu
- Kidney Research Institute, Department of Nephrology, West China Hospital of Sichuan University, Sichuan, Chengdu, 610041, China.
| | - Liang Ma
- Kidney Research Institute, Department of Nephrology, West China Hospital of Sichuan University, Sichuan, Chengdu, 610041, China.
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Harkin C, Smith KW, MacKay CL, Moore T, Brockbank S, Ruddock M, Cobice DF. Spatial localization of β-unsaturated aldehyde markers in murine diabetic kidney tissue by mass spectrometry imaging. Anal Bioanal Chem 2022; 414:6657-6670. [PMID: 35881173 PMCID: PMC9411223 DOI: 10.1007/s00216-022-04229-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 07/04/2022] [Accepted: 07/12/2022] [Indexed: 11/09/2022]
Abstract
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Limitations in current diagnosis and screening methods have sparked a search for more specific and conclusive biomarkers. Hyperglycemic conditions generate a plethora of harmful molecules in circulation and within tissues. Oxidative stress generates reactive α-dicarbonyls and β-unsaturated hydroxyhexenals, which react with proteins to form advanced glycation end products. Mass spectrometry imaging (MSI) enables the detection and spatial localization of molecules in biological tissue sections. Here, for the first time, the localization and semiquantitative analysis of “reactive aldehydes” (RAs) 4-hydroxyhexenal (4-HHE), 4-hydroxynonenal (4-HNE), and 4-oxo-2-nonenal (4-ONE) in the kidney tissues of a diabetic mouse model is presented. Ionization efficiency was enhanced through on-tissue chemical derivatization (OTCD) using Girard’s reagent T (GT), forming positively charged hydrazone derivatives. MSI analysis was performed using matrix-assisted laser desorption ionization (MALDI) coupled with Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR). RA levels were elevated in diabetic kidney tissues compared to lean controls and localized throughout the kidney sections at a spatial resolution of 100 µm. This was confirmed by liquid extraction surface analysis–MSI (LESA-MSI) and liquid chromatography–mass spectrometry (LC–MS). This method identified β-unsaturated aldehydes as “potential” biomarkers of DN and demonstrated the capability of OTCD-MSI for detection and localization of poorly ionizable molecules by adapting existing chemical derivatization methods. Untargeted exploratory distribution analysis of some precursor lipids was also assessed using MALDI-FT-ICR-MSI.
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Affiliation(s)
- Carla Harkin
- Mass Spectrometry Centre, Biomedical Sciences Research Institute (BMSRI), School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, UK
| | - Karl W Smith
- National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, 32310-4005, USA.,Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V., Dortmund, Germany
| | - C Logan MacKay
- Scottish Instrumentation and Research Centre for Advanced Mass Spectrometry (SIRCAMS), EastChem School of Chemistry, University of Edinburgh, Edinburgh, Scotland, UK
| | - Tara Moore
- Genomic Medicine, Biomedical Sciences Research Institute (BMSRI), School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, UK
| | | | - Mark Ruddock
- Randox Laboratories Ltd, 55 The Diamond Rd, Crumlin, UK
| | - Diego F Cobice
- Mass Spectrometry Centre, Biomedical Sciences Research Institute (BMSRI), School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, UK.
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Oxidative Stress and Lipid Dysregulation in Lipid Droplets: A Connection to Chronic Kidney Disease Revealed in Human Kidney Cells. Antioxidants (Basel) 2022; 11:antiox11071387. [PMID: 35883878 PMCID: PMC9312214 DOI: 10.3390/antiox11071387] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 07/10/2022] [Accepted: 07/14/2022] [Indexed: 02/04/2023] Open
Abstract
Chronic kidney disease (CKD), which is defined as a condition causing the gradual loss of kidney function, shows renal lipid droplet (LD) accumulation that is associated with oxidative damage. There is a possibility that an LD abnormality in quality plays a role in CKD development. This study aimed to explore the chemical composition of LDs that are induced in human kidney cells during exposure to free fatty acids as an LD source and oxidized lipoproteins as oxidative stress. The LDs were aspirated directly from cells using nanotips, followed by in-tip microextraction, and the LD lipidomic profiling was conducted using nanoelectrospray mass spectrometry. As a result, the free fatty acids increased the LD lipid content and, at the same time, changed their composition significantly. The oxidized lipoproteins caused distorted proportions of intact lipids, such as triacylglycerols (TG), phosphatidylcholines (PC), phosphatidylethanolamines (PE), and cholesteryl esters (CE). Notably, the oxidized lipids, including the hydroperoxides of TG, PC, and PE, exhibited significant elevations in dose-dependent manners. Furthermore, the dysregulation of intact lipids was paralleled with the accumulation of lipid hydroperoxides. The present study has revealed that the oxidation of lipids and the dysregulation of the lipid metabolism coexisted in LDs in the kidney cells, which has provided a potential new target for diagnosis and new insights into CKD.
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Zhang Z, Zheng R, Zhu C, Geng H, Xu G. Lipidomics characterization of the lipid metabolism profiles in a cystinuria rat model: Precalculus damage in the kidney of cystinuria. Prostaglandins Other Lipid Mediat 2022; 162:106651. [PMID: 35680078 DOI: 10.1016/j.prostaglandins.2022.106651] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 05/20/2022] [Accepted: 06/02/2022] [Indexed: 10/18/2022]
Abstract
Cystinuria is a genetic disorder of cystine transport, including defective protein b0,+AT (encoded by SLC7A9), and/or rBAT (encoded by SLC3A1). Patients present hyperexcretion of cystine in the urine, recurrent cystine lithiasis, and progressive decline in kidney function. Moreover, heterodimer transport is defective. To date, little omics data are accessible regarding this metabolic disease caused by membrane proteins. Since membrane function is closely related to changes in the lipidome, we decided to explore the changes in kidney tissue of a self-established cystinuria rat model by performing lipidomic analysis by LC-MS/MS. Our results demonstrated that Slc7a9 deficiency changed the lipid profile of the renal cortex and induced vital modifications in the lipidome, including major alterations in ChE, LPA, and PA. Among those alterations, this lipidomic study highlights the lipid changes that participate in inflammatory responses during cystinuria. As a result, lipid research, perhaps has great potential, for it may lead to the identification of novel therapeutic targets for the prevention and treatment of cystinuria.
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Affiliation(s)
- Zihan Zhang
- Shanghai Jiaotong University School of Medicine, China
| | - Rui Zheng
- Department of Pediatric Urology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China
| | - Caihua Zhu
- Shanghai Applied Protein Technology Co., Ltd., 201100, China
| | - Hongquan Geng
- Shanghai Jiaotong University School of Medicine, China; Department of Pediatric Urology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China.
| | - Guofeng Xu
- Shanghai Jiaotong University School of Medicine, China; Department of Pediatric Urology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China.
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Bier A, Shapira E, Khasbab R, Sharabi Y, Grossman E, Leibowitz A. High-Fructose Diet Increases Renal ChREBPβ Expression, Leading to Intrarenal Fat Accumulation in a Rat Model with Metabolic Syndrome. BIOLOGY 2022; 11:biology11040618. [PMID: 35453816 PMCID: PMC9027247 DOI: 10.3390/biology11040618] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 04/07/2022] [Accepted: 04/14/2022] [Indexed: 01/07/2023]
Abstract
Simple Summary Fructose consumption leads to the development of metabolic syndrome. Fatty liver and chronic kidney disease are closely related to metabolic syndrome. Lately, a transcription factor that regulates fructose metabolism in the liver, named ChREBPβ, which is responsible for de-novo lipogenesis and intra-hepatic fat accumulation (“fatty liver”), was described. In this study, we demonstrate that the effect of fructose consumption on the kidneys resembles its liver effect. Rats fed with a high-fructose diet exhibit bigger kidneys with higher triglycerides content, compared to control rats. The expression of ChREBPβ and its downstream genes was upregulated as well. Treating kidney-origin cells with fructose increased the expression of this factor as well, showing the direct effect of fructose on this factor. Thus, the appearance of fatty kidney in response to high-fructose consumption revealed a new mechanism linking metabolic syndrome to chronic kidney disease. Abstract Fructose consumption is associated with metabolic syndrome (MeS). Dysregulated lipid metabolism and ectopic lipid accumulation, such as in “fatty liver’’, are pivotal components of the syndrome. MeS is also associated with chronic kidney disease (CKD). The aim of this study was to evaluate kidney fructose metabolism and whether the addition of fructose leads to intrarenal fat accumulation. Sprague Dawley rats were fed either normal chow (Ctrl) or a high-fructose diet (HFrD). MeS features such as blood pressure and metabolic parameters in blood were measured. The kidneys were harvested for ChREBPβ and de novo lipogenesis (DNL) gene expression, triglyceride content and histopathology staining. HK2 (human kidney) cells were treated with fructose for 48 h and gene expression for ChREBPβ and DNL were determined. The HFrD rats exhibited higher blood pressure, glucose and triglyceride levels. The kidney weight of the HFrD rats was significantly higher than Ctrl rats. The difference can be explained by the higher triglyceride content in the HFrD kidneys. Oil red staining revealed lipid droplet formation in the HFrD kidneys, which was also supported by increased adipophilin mRNA expression. For ChREBPβ and its downstream genes, scd and fasn, mRNA expression was elevated in the HFrD kidneys. Treating HK2 cells with 40 mM fructose increased the expression of ChREBPβ. This study demonstrates that fructose consumption leads to intrarenal lipid accumulation and to the formation of a “fatty kidney”. This suggests a potential mechanism that can at least partially explain CKD development in fructose-induced MeS.
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Affiliation(s)
- Ariel Bier
- Medicine D, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262000, Israel; (A.B.); (E.S.); (Y.S.); (E.G.)
| | - Eliyahu Shapira
- Medicine D, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262000, Israel; (A.B.); (E.S.); (Y.S.); (E.G.)
- Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel
| | - Rawan Khasbab
- Hypertension Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262000, Israel;
| | - Yehonatan Sharabi
- Medicine D, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262000, Israel; (A.B.); (E.S.); (Y.S.); (E.G.)
- Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel
- Hypertension Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262000, Israel;
| | - Ehud Grossman
- Medicine D, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262000, Israel; (A.B.); (E.S.); (Y.S.); (E.G.)
- Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel
- Hypertension Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262000, Israel;
| | - Avshalom Leibowitz
- Medicine D, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262000, Israel; (A.B.); (E.S.); (Y.S.); (E.G.)
- Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel
- Hypertension Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262000, Israel;
- Correspondence: ; Tel.: +972-35302834; Fax: +972-35302835
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Wu X, Chen Z, Wu Y, Chen Y, Jia J, Shen N, Chiba H, Hui SP. Flazin as a Lipid Droplet Regulator against Lipid Disorders. Nutrients 2022; 14:1501. [PMID: 35406114 PMCID: PMC9002757 DOI: 10.3390/nu14071501] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 03/28/2022] [Accepted: 04/01/2022] [Indexed: 12/20/2022] Open
Abstract
Lipid disorders are closely related to numerous metabolic diseases, and lipid droplets (LDs) have been considered as a new target for regulating lipid metabolism. Dietary intervention and nutraceuticals provide safe and long-term beneficial effects for treating metabolic diseases. Flazin is a diet-derived bioactive constituent mainly existing in fermented foods, of which the lipid metabolism improvement function has not been studied. In this study, the effect of flazin on lipid regulation at both cell level and organelle level was investigated. Lipidomic profiling showed that flazin significantly decreased cellular triglyceride (TG) by 12.0-22.4% compared with modeling groups and improved the TG and free fatty acid profile. LD staining revealed that flazin efficiently reduced both cellular neutral lipid content by 17.4-53.9% and LD size by 10.0-35.3%. Furthermore, nanoelectrospray ionization mass spectrometry analysis proved that flazin exhibited a preferential suppression of LD TG and regulated LD morphology, including a size decrease and surface property improvement. An evaluation of related gene expression suggested the mechanism to be lipolysis promotion and lipogenesis inhibition. These findings indicated that flazin might be an LD regulator for reversing lipid metabolism disturbance. Moreover, the strategy proposed in this study may contribute to developing other nutraceuticals for treating lipid disorder-related metabolic diseases.
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Affiliation(s)
- Xunzhi Wu
- Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo 060-0812, Japan; (X.W.); (Z.C.); (Y.W.); (Y.C.); (J.J.); (N.S.)
| | - Zhen Chen
- Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo 060-0812, Japan; (X.W.); (Z.C.); (Y.W.); (Y.C.); (J.J.); (N.S.)
| | - Yue Wu
- Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo 060-0812, Japan; (X.W.); (Z.C.); (Y.W.); (Y.C.); (J.J.); (N.S.)
| | - Yifan Chen
- Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo 060-0812, Japan; (X.W.); (Z.C.); (Y.W.); (Y.C.); (J.J.); (N.S.)
| | - Jiaping Jia
- Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo 060-0812, Japan; (X.W.); (Z.C.); (Y.W.); (Y.C.); (J.J.); (N.S.)
| | - Nianqiu Shen
- Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo 060-0812, Japan; (X.W.); (Z.C.); (Y.W.); (Y.C.); (J.J.); (N.S.)
| | - Hitoshi Chiba
- Department of Nutrition, Sapporo University of Health Sciences, Nakanuma Nishi-4-2-1-15, Higashi-ku, Sapporo 007-0894, Japan;
| | - Shu-Ping Hui
- Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo 060-0812, Japan; (X.W.); (Z.C.); (Y.W.); (Y.C.); (J.J.); (N.S.)
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Role of Distinct Fat Depots in Metabolic Regulation and Pathological Implications. Rev Physiol Biochem Pharmacol 2022; 186:135-176. [PMID: 35915363 DOI: 10.1007/112_2022_73] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
People suffering from obesity and associated metabolic disorders including diabetes are increasing exponentially around the world. Adipose tissue (AT) distribution and alteration in their biochemical properties play a major role in the pathogenesis of these diseases. Emerging evidence suggests that AT heterogeneity and depot-specific physiological changes are vital in the development of insulin resistance in peripheral tissues like muscle and liver. Classically, AT depots are classified into white adipose tissue (WAT) and brown adipose tissue (BAT); WAT is the site of fatty acid storage, while BAT is a dedicated organ of metabolic heat production. The discovery of beige adipocyte clusters in WAT depots indicates AT heterogeneity has a more central role than hither to ascribed. Therefore, we have discussed in detail the current state of understanding on cellular and molecular origin of different AT depots and their relevance toward physiological metabolic homeostasis. A major focus is to highlight the correlation between altered WAT distribution in the body and metabolic pathogenesis in animal models and humans. We have also underscored the disparity in the molecular (including signaling) changes in various WAT tissues during diabetic pathogenesis. Exercise-mediated beneficial alteration in WAT physiology/distribution that protects against metabolic disorders is evolving. Here we have discussed the depot-specific biochemical adjustments induced by different forms of exercise. A detailed understanding of the molecular details of inter-organ crosstalk via substrate utilization/storage and signaling through chemokines provide strategies to target selected WAT depots to pharmacologically mimic the benefits of exercise countering metabolic diseases including diabetes.
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Zhan Z, Li A, Zhang W, Wu X, He J, Li Z, Li Y, Sun J, Zhang H. ATP-citrate lyase inhibitor improves ectopic lipid accumulation in the kidney in a db/db mouse model. Front Endocrinol (Lausanne) 2022; 13:914865. [PMID: 36568100 PMCID: PMC9771989 DOI: 10.3389/fendo.2022.914865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 11/11/2022] [Indexed: 12/12/2022] Open
Abstract
AIM We evaluated a novel treatment for obesity-related renal, an ATP-citrate lyase (ACL) inhibitor, to attenuate ectopic lipid accumulation (ELA) in the kidney and the ensuing inflammation. MATERIALS AND METHODS An ACL inhibitor was administered intragastrically to 12-week-old db/db mice for 30 days. The appearance of ELA was observed by staining kidney sections with Oil Red O, and the differences in tissue lipid metabolites were assessed by mass spectrometry. The anti-obesity and renoprotection effects of ACL inhibitors were observed by histological examination and multiple biochemical assays. RESULTS Using the AutoDock Vina application, we determined that among the four known ACL inhibitors (SB-204990, ETC-1002, NDI-091143, and BMS-303141), BMS-303141 had the highest affinity for ACL and reduced ACL expression in the kidneys of db/db mice. We reported that BMS-303141 administration could decrease the levels of serum lipid and renal lipogenic enzymes acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), HMG-CoA reductase (HMGCR), and diminish renal ELA in db/db mice. In addition, we found that reducing ELA improved renal injuries, inflammation, and tubulointerstitial fibrosis. CONCLUSION ACL inhibitor BMS-303141 protects against obesity-related renal injuries.
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Affiliation(s)
- Zishun Zhan
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- The Critical Kidney Disease Research Center of Central South University, Changsha, Hunan, China
| | - Aimei Li
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- The Critical Kidney Disease Research Center of Central South University, Changsha, Hunan, China
| | - Wei Zhang
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- The Critical Kidney Disease Research Center of Central South University, Changsha, Hunan, China
| | - Xueqin Wu
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- The Critical Kidney Disease Research Center of Central South University, Changsha, Hunan, China
| | - Jinrong He
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- The Critical Kidney Disease Research Center of Central South University, Changsha, Hunan, China
| | - Zhi Li
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- The Critical Kidney Disease Research Center of Central South University, Changsha, Hunan, China
| | - Yanchun Li
- Division of Biological Sciences, Department of Medicine, University of Chicago, Chicago, Chicago, IL, United States
| | - Jian Sun
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- The Critical Kidney Disease Research Center of Central South University, Changsha, Hunan, China
- Department of Rheumatology and Immunology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- *Correspondence: Hao Zhang, ; Jian Sun,
| | - Hao Zhang
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- The Critical Kidney Disease Research Center of Central South University, Changsha, Hunan, China
- *Correspondence: Hao Zhang, ; Jian Sun,
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Borer KT. Why We Eat Too Much, Have an Easier Time Gaining Than Losing Weight, and Expend Too Little Energy: Suggestions for Counteracting or Mitigating These Problems. Nutrients 2021; 13:3812. [PMID: 34836068 PMCID: PMC8618649 DOI: 10.3390/nu13113812] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 10/13/2021] [Accepted: 10/19/2021] [Indexed: 12/11/2022] Open
Abstract
The intent of this review is to survey physiological, psychological, and societal obstacles to the control of eating and body weight maintenance and offer some evidence-based solutions. Physiological obstacles are genetic and therefore not amenable to direct abatement. They include an absence of feedback control against gaining weight; a non-homeostatic relationship between motivations to be physically active and weight gain; dependence of hunger and satiation on the volume of food ingested by mouth and processed by the gastrointestinal tract and not on circulating metabolites and putative hunger or satiation hormones. Further, stomach size increases from overeating and binging, and there is difficulty in maintaining weight reductions due to a decline in resting metabolism, increased hunger, and enhanced efficiency of energy storage. Finally, we bear the evolutionary burden of extraordinary human capacity to store body fat. Of the psychological barriers, human craving for palatable food, tendency to overeat in company of others, and gullibility to overeat when offered large portions, can be overcome consciously. The tendency to eat an unnecessary number of meals during the wakeful period can be mitigated by time-restricted feeding to a 6-10 hour period. Social barriers of replacing individual physical work by labor-saving appliances, designing built environments more suitable for car than active transportation; government food macronutrient advice that increases insulin resistance; overabundance of inexpensive food; and profit-driven efforts by the food industry to market energy-dense and nutritionally compromised food are best overcome by informed individual macronutrient choices and appropriate timing of exercise with respect to meals, both of which can decrease insulin resistance. The best defense against overeating, weight gain, and inactivity is the understanding of factors eliciting them and of strategies that can avoid and mitigate them.
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Affiliation(s)
- Katarina T Borer
- School of Kinesiology, The University of Michigan, Ann Arbor, MI 48104, USA
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Escasany E, Lanzón B, García-Carrasco A, Izquierdo-Lahuerta A, Torres L, Corrales P, Rodríguez Rodríguez AE, Luis-Lima S, Martínez Álvarez C, Javier Ruperez F, Ros M, Porrini E, Rydén M, Medina-Gómez G. Transforming growth factor β3 deficiency promotes defective lipid metabolism and fibrosis in murine kidney. Dis Model Mech 2021; 14:271939. [PMID: 34431499 PMCID: PMC8489029 DOI: 10.1242/dmm.048249] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 07/27/2021] [Indexed: 01/06/2023] Open
Abstract
Glomerulosclerosis and tubulointerstitial fibrosis are pathological features of chronic kidney disease. Transforming growth factor β (TGFβ) is a key player in the development of fibrosis. However, of the three known TGFβ isoforms, only TGFβ1 has an established role in fibrosis, and the pathophysiological relevance of TGFβ2 and TGFβ3 is unknown. Because Tgfb3 deficiency in mice results in early postnatal lethality, we analyzed the kidney phenotype of heterozygous Tgfb3-knockout mice (Tgfb3+/−) and compared it with that of matched wild-type mice. Four-month-old Tgfb3+/− mice exhibited incipient renal fibrosis with epithelial–mesenchymal transition, in addition to glomerular basement membrane thickening and podocyte foot process effacement associated with albuminuria. Also evident was insulin resistance and oxidative stress at the renal level, together with aberrant renal lipid metabolism and mitochondrial function. Omics analysis revealed toxic species, such as diacylglycerides and ceramides, and dysregulated mitochondrial metabolism in Tgfb3+/− mice. Kidneys of Tgfb3+/− mice showed morphological alterations of mitochondria and overactivation of non-canonical MAPK ERK1/2 and JNK cascades. Our study indicates that renal TGFβ3 might have antifibrotic and renoprotective properties, opposing or counteracting the activity of TGFβ1. This article has an associated First Person interview with the first author of the paper. Summary: Our study describes the renal abnormalities of heterozygous Tgfb3-targeted mice and suggests that TGFβ3 is renoprotective and may counteract the activity of TGFβ1.
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Affiliation(s)
- Elia Escasany
- Lipobeta group, Área de Bioquímica y Biología Molecular, Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Avda. de Atenas s/n, Alcorcón, 28922 Madrid, Spain
| | - Borja Lanzón
- Lipobeta group, Área de Bioquímica y Biología Molecular, Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Avda. de Atenas s/n, Alcorcón, 28922 Madrid, Spain
| | - Almudena García-Carrasco
- Lipobeta group, Área de Bioquímica y Biología Molecular, Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Avda. de Atenas s/n, Alcorcón, 28922 Madrid, Spain
| | - Adriana Izquierdo-Lahuerta
- Lipobeta group, Área de Bioquímica y Biología Molecular, Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Avda. de Atenas s/n, Alcorcón, 28922 Madrid, Spain
| | - Lucía Torres
- Lipobeta group, Área de Bioquímica y Biología Molecular, Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Avda. de Atenas s/n, Alcorcón, 28922 Madrid, Spain
| | - Patricia Corrales
- Lipobeta group, Área de Bioquímica y Biología Molecular, Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Avda. de Atenas s/n, Alcorcón, 28922 Madrid, Spain
| | | | - Sergio Luis-Lima
- IIS-Fundación Jiménez Díaz, Departamento de Nefrología e Hipertensión, 28040 Madrid, Spain
| | - Concepción Martínez Álvarez
- Departamento de Anatomía y Embriología, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - Francisco Javier Ruperez
- Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Boadilla del Monte, 28660 Madrid, Spain
| | - Manuel Ros
- Lipobeta group, Área de Bioquímica y Biología Molecular, Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Avda. de Atenas s/n, Alcorcón, 28922 Madrid, Spain
| | - Esteban Porrini
- Universidad La Laguna, Instituto Tecnologías Biomédicas (ITB), 38200 La Laguna, Tenerife, Spain
| | - Mikael Rydén
- Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, 141 86 Stockholm, Sweden
| | - Gema Medina-Gómez
- Lipobeta group, Área de Bioquímica y Biología Molecular, Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Avda. de Atenas s/n, Alcorcón, 28922 Madrid, Spain.,LAFEMEX laboratory, Área de Bioquímica y Biología Molecular, Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Avda. de Atenas s/n, Alcorcón, 28922 Madrid, Spain
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Sharma I, Liao Y, Zheng X, Kanwar YS. New Pandemic: Obesity and Associated Nephropathy. Front Med (Lausanne) 2021; 8:673556. [PMID: 34268323 PMCID: PMC8275856 DOI: 10.3389/fmed.2021.673556] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 05/28/2021] [Indexed: 12/12/2022] Open
Abstract
Incidence of obesity related renal disorders have increased 10-folds in recent years. One of the consequences of obesity is an increased glomerular filtration rate (GFR) that leads to the enlargement of the renal glomerulus, i.e., glomerulomegaly. This heightened hyper-filtration in the setting of type 2 diabetes irreparably damages the kidney and leads to progression of end stage renal disease (ESRD). The patients suffering from type 2 diabetes have progressive proteinuria, and eventually one third of them develop chronic kidney disease (CKD) and ESRD. For ameliorating the progression of CKD, inhibitors of renin angiotensin aldosterone system (RAAS) seemed to be effective, but on a short-term basis only. Long term and stable treatment strategies like weight loss via restricted or hypo-caloric diet or bariatric surgery have yielded better promising results in terms of amelioration of proteinuria and maintenance of normal GFR. Body mass index (BMI) is considered as a traditional marker for the onset of obesity, but apparently, it is not a reliable indicator, and thus there is a need for more precise evaluation of regional fat distribution and amount of muscle mass. With respect to the pathogenesis, recent investigations have suggested perturbation in fatty acid and cholesterol metabolism as the critical mediators in ectopic renal lipid accumulation associated with inflammation, increased generation of ROS, RAAS activation and consequential tubulo-interstitial injury. This review summarizes the renewed approaches for the obesity assessment and evaluation of the pathogenesis of CKD, altered renal hemodynamics and potential therapeutic targets.
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Affiliation(s)
- Isha Sharma
- Departments of Pathology and Medicine, Northwestern University, Chicago, IL, United States
| | - Yingjun Liao
- Departments of Pathology and Medicine, Northwestern University, Chicago, IL, United States.,Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, China
| | - Xiaoping Zheng
- Departments of Pathology and Medicine, Northwestern University, Chicago, IL, United States.,Department of Urology, Third Xiangya Hospital, Central South University, Changsha, China
| | - Yashpal S Kanwar
- Departments of Pathology and Medicine, Northwestern University, Chicago, IL, United States
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Xia X, Wang X, Wang H, Lin Z, Shao K, Xu J, Zhao Y. Ameliorative effect of white tea from 50-year-old tree of Camellia sinensis L. (Theaceae) on kidney damage in diabetic mice via SIRT1/AMPK pathway. JOURNAL OF ETHNOPHARMACOLOGY 2021; 272:113919. [PMID: 33577915 DOI: 10.1016/j.jep.2021.113919] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 01/26/2021] [Accepted: 02/06/2021] [Indexed: 06/12/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Diabetic kidney damage (DKD) is one of the most common complications of diabetes, which is known as a chronic inflammatory kidney disease caused by persistent hyperglycemia. White tea was originally used as a folk medicine to treat measles in ancient China. What arouses our interest is that there is a traditional method to treat diabetes with white tea taken from over 30-year-old tree of Camellia sinensis L. However, there are few reports on the renal protection of white tea. AIM OF THE STUDY This present study was designed to study the potential protective effects of white tea (WT) and old tree white tea (OTWT) on high-fat-diet (HFD) combined with streptozotocin (STZ)-induced type 2 diabetic mice to explore the possible mechanism of WT/OTWT against DKD. MATERIALS AND METHODS C57BL/6 mice were randomly divided into four groups: NC, T2D, WT (400 mg/kg·b.w, p.o.), OTWT (400 mg/kg·b.w, p.o.). Diabetes was established in all groups except NC group, by six weeks of HFD feeding combined with STZ (50 mg/kg, i.p.) for 3 times, treatments were administered for six weeks and then all the animals were decapitated; kidney tissues and blood samples were collected for the further analysis, including: levels of insulin, lipid metabolism (TG, TC, HDL, LDL, FFA), antioxidative enzymes (catalase (CAT), super oxide dismutase (SOD), glutathione peroxidase (GPx)), blood urea nitrogen (BUN) and creatine, inflammatory cytokines (TNF-α, IL-1β, COX-2, iNOS, MCP-1), advanced glycation end products (AGE), receptor of AGE (RAGE), Nrf2, AMPK, SIRT1, and PGC-1α. H&E, PAS and Masson staining were performed to examine the histopathological alterations of the kidneys. RESULTS Our data showed that WT and OTWT reversed the abnormal serum lipids (TG, TC, HDL, LDL, FFA) in T2D mice, upregulated antioxidative enzymes levels (CAT, SOD, GPx) and inhibit the excessive production of proinflammatory mediators (including MCP-1, TNF-α, IL1β, COX-2 and iNOS) by varying degrees, and OTWT was more effective. In histopathology, OTWT could significantly alleviate the accumulation of renal AGE in T2D mice, thereby improving the structural changes of the kidneys, such as glomerular hypertrophy, glomerular basement membrane thickening and kidney FIbrosis. CONCLUSIONS Both WT and OTWT could alleviate the diabetic changes in T2D mice via hypoglycemic, hypolipidemic, anti-oxidative and anti-inflammatory effects, while OTWT was more evident. OTWT could prominently alleviate the accumulation of AGE in the kidneys of T2D mice, thereby ameliorating the renal oxidative stress and inflammatory damage, which was associated with the activation of SIRT1/AMPK pathway.
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Affiliation(s)
- Xiaoyan Xia
- School of Traditional Chinese Medicine, Shanxi Datong University, Datong, 037009, China; School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, China.
| | - Xude Wang
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, China.
| | - Hua Wang
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, China.
| | - Zhenchuan Lin
- Pinpin Tea Industry Co., Ltd., Fujian, 355200, China.
| | - Keping Shao
- Pinpin Tea Industry Co., Ltd., Fujian, 355200, China.
| | - Jing Xu
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, China.
| | - Yuqing Zhao
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, China; Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China.
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Wu M, Yang Z, Zhang C, Shi Y, Han W, Song S, Mu L, Du C, Shi Y. Inhibition of NLRP3 inflammasome ameliorates podocyte damage by suppressing lipid accumulation in diabetic nephropathy. Metabolism 2021; 118:154748. [PMID: 33675822 DOI: 10.1016/j.metabol.2021.154748] [Citation(s) in RCA: 89] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 02/18/2021] [Accepted: 02/27/2021] [Indexed: 01/19/2023]
Abstract
BACKGROUND Nucleotide leukin-rich polypeptide 3 (NLRP3) inflammasome is documented as a potent target for treating metabolic diseases and inflammatory disorders. Our recent work demonstrated that inhibition of NLRP3 inflammasome activation inhibits renal inflammation and fibrosis in diabetic nephropathy. This study was to investigate the effect of NLRP3 inflammasome on podocyte injury and the underlying mechanism in diabetic nephropathy. METHODS In vivo, db/db mice were treated with MCC950, a NLRP3 inflammasome specific inhibitor. NLRP3 knockout (NKO) mice were induced to diabetes by intraperitoneal injections of streptozotocin (STZ). We assessed renal function, albuminuria, podocyte injury and glomerular lipid accumulation in diabetic mice. In vitro, apoptosis, cytoskeleton change, lipid accumulation, NF-κB p65 activation and reactive oxygen species (ROS) generation were evaluated in podocytes interfered with NLRP3 siRNA or MCC950 under high glucose (HG) conditions. In addition, the effect and mechanism of IL-1β on lipid accumulation was explored in podocytes exposed to normal glucose (NG) or HG. RESULTS MCC950 treatment improved renal function, attenuated albuminuria, mesangial expansion, podocyte loss, as well as glomerular lipid accumulation in db/db mice. The diabetes-induced podocyte loss and glomerular lipid accumulation were reversed in NLRP3 knockout mice. The increased expression of sterol regulatory element-binding protein1 (SREBP1) and SREBP2, and decreased expression of ATP-binding cassette A1 (ABCA1) in podocytes were reversed by MCC950 treatment or NLRP3 knockout in diabetic mice. In vitro, NLRP3 siRNA or MCC950 treatment markedly inhibited HG-induced apoptosis, cytoskeleton change, lipid accumulation, NF-κB p65 activation, and mitochondrial ROS production in cultured podocytes. In addition, BAY11-7082 or tempol treatment inhibited HG-induced lipid accumulation in podocytes. Moreover, exposure of IL-1β to podocytes induced lipid accumulation, NF-κB p65 activation and mitochondrial ROS generation. CONCLUSION Inhibition of NLRP3 inflammasome protects against podocyte damage through suppression of lipid accumulation in diabetic nephropathy. IL-1β/ROS/NF-κB p65 mediates diabetes-associated lipid accumulation in podocytes. The suppression of NLRP3 inflammasome activation may be an effective therapeutic approach to diabetic nephropathy.
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Affiliation(s)
- Ming Wu
- Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Laboratory of Kidney Disease, Shijiazhuang 050017, China
| | - Zhifen Yang
- Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China
| | - Chengyu Zhang
- Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China
| | - Yu Shi
- Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China
| | - Weixia Han
- Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China
| | - Shan Song
- Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Laboratory of Kidney Disease, Shijiazhuang 050017, China; Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China
| | - Lin Mu
- Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Laboratory of Kidney Disease, Shijiazhuang 050017, China
| | - Chunyang Du
- Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Laboratory of Kidney Disease, Shijiazhuang 050017, China; Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China
| | - Yonghong Shi
- Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Laboratory of Kidney Disease, Shijiazhuang 050017, China; Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang 050017, China.
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Chung KW. Advances in Understanding of the Role of Lipid Metabolism in Aging. Cells 2021; 10:cells10040880. [PMID: 33924316 PMCID: PMC8068994 DOI: 10.3390/cells10040880] [Citation(s) in RCA: 88] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 04/09/2021] [Accepted: 04/12/2021] [Indexed: 02/06/2023] Open
Abstract
During aging, body adiposity increases with changes in the metabolism of lipids and their metabolite levels. Considering lipid metabolism, excess adiposity with increased lipotoxicity leads to various age-related diseases, including cardiovascular disease, cancer, arthritis, type 2 diabetes, and Alzheimer's disease. However, the multifaceted nature and complexities of lipid metabolism make it difficult to delineate its exact mechanism and role during aging. With advances in genetic engineering techniques, recent studies have demonstrated that changes in lipid metabolism are associated with aging and age-related diseases. Lipid accumulation and impaired fatty acid utilization in organs are associated with pathophysiological phenotypes of aging. Changes in adipokine levels contribute to aging by modulating changes in systemic metabolism and inflammation. Advances in lipidomic techniques have identified changes in lipid profiles that are associated with aging. Although it remains unclear how lipid metabolism is regulated during aging, or how lipid metabolites impact aging, evidence suggests a dynamic role for lipid metabolism and its metabolites as active participants of signaling pathways and regulators of gene expression. This review describes recent advances in our understanding of lipid metabolism in aging, including established findings and recent approaches.
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Affiliation(s)
- Ki Wung Chung
- College of Pharmacy, Pusan National University, Busan 46214, Korea
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47
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Ghosh SS, Wang J, Yannie PJ, Cooper RC, Sandhu YK, Kakiyama G, Korzun WJ, Ghosh S. Over-Expression of Intestinal Alkaline Phosphatase Attenuates Atherosclerosis. Circ Res 2021; 128:1646-1659. [PMID: 33834851 DOI: 10.1161/circresaha.120.317144] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
[Figure: see text].
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Affiliation(s)
- Siddhartha S Ghosh
- Internal Medicine (S.S.G., J.W., Y.K.S., G.K., S.G.), Virginia Commonwealth University (VCU) Medical Center, Richmond, VA
| | - Jing Wang
- Internal Medicine (S.S.G., J.W., Y.K.S., G.K., S.G.), Virginia Commonwealth University (VCU) Medical Center, Richmond, VA
| | - Paul J Yannie
- Hunter Homes McGuire VA Medical Center, Richmond (P.J.Y., G.K., S.G.)
| | | | - Yashnoor K Sandhu
- Internal Medicine (S.S.G., J.W., Y.K.S., G.K., S.G.), Virginia Commonwealth University (VCU) Medical Center, Richmond, VA
| | - Genta Kakiyama
- Internal Medicine (S.S.G., J.W., Y.K.S., G.K., S.G.), Virginia Commonwealth University (VCU) Medical Center, Richmond, VA.,Hunter Homes McGuire VA Medical Center, Richmond (P.J.Y., G.K., S.G.)
| | - William J Korzun
- Clinical and Laboratory Sciences (W.J.K.), Virginia Commonwealth University (VCU) Medical Center, Richmond, VA
| | - Shobha Ghosh
- Internal Medicine (S.S.G., J.W., Y.K.S., G.K., S.G.), Virginia Commonwealth University (VCU) Medical Center, Richmond, VA.,Hunter Homes McGuire VA Medical Center, Richmond (P.J.Y., G.K., S.G.)
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48
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Sulforaphane prevents type 2 diabetes-induced nephropathy via AMPK-mediated activation of lipid metabolic pathways and Nrf2 antioxidative function. Clin Sci (Lond) 2021; 134:2469-2487. [PMID: 32940670 DOI: 10.1042/cs20191088] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Revised: 09/16/2020] [Accepted: 09/17/2020] [Indexed: 12/12/2022]
Abstract
Sulforaphane (SFN) prevents diabetic nephropathy (DN) in type 2 diabetes (T2D) by up-regulating nuclear factor (erythroid-derived 2)-like 2 (Nrf2). AMP-activated protein kinase (AMPK) can attenuate the pathogenesis of DN by improving renal lipotoxicity along with the activation of Nrf2-mediated antioxidative signaling. Therefore, we investigated whether AMPKα2, the central subunit of AMPK in energy metabolism, is required for SFN protection against DN in T2D, and whether potential cross-talk occurs between AMPKα2 and Nrf2. AMPKα2 knockout (Ampkα2-/-) mice and wildtype (WT) mice were fed a high-fat diet (HFD) or a normal diet (ND) to induce insulin resistance, followed by streptozotocin (STZ) injection to induce hyperglycemia, as a T2D model. Both T2D and control mice were treated with SFN or vehicle for 3 months. At the end of the 3-month treatment, all mice were maintained only on HFD or ND for an additional 3 months without SFN treatment. Mice were killed at sixth month after T2D onset. Twenty-four-hour urine albumin at third and sixth months was significantly increased as renal dysfunction, along with significant renal pathological changes and biochemical changes including renal hypertrophy, oxidative damage, inflammation, and fibrosis in WT T2D mice, which were prevented by SFN in certain contexts, but not in Ampkα2-/- T2D mice. SFN prevention of T2D-induced renal lipotoxicity was associated with AMPK-mediated activation of lipid metabolism and Nrf2-dependent antioxidative function in WT mice, but not in SFN-treated Ampkα2-/- mice. Therefore, SFN prevention of DN is AMPKα2-mediated activation of probably both lipid metabolism and Nrf2 via AMPK/AKT/glycogen synthase kinase (GSK)-3β/Src family tyrosine kinase (Fyn) pathways.
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Gao L, Yang TT, Zhang JS, Liu HX, Cai DC, Wang LT, Wang J, Li XW, Gao K, Zhang SY, Cao YJ, Ji XX, Yang MM, Han B, Wang S, He L, Nie XY, Liu DM, Meng G, He CY. THBS1/CD47 Modulates the Interaction of γ-Catenin With E-Cadherin and Participates in Epithelial-Mesenchymal Transformation in Lipid Nephrotoxicity. Front Cell Dev Biol 2021; 8:601521. [PMID: 33681182 PMCID: PMC7930485 DOI: 10.3389/fcell.2020.601521] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 12/31/2020] [Indexed: 12/28/2022] Open
Abstract
Hyperlipidemia, an important risk factor for cardiovascular and end-stage renal diseases, often aggravates renal injury and compromises kidney function. Here, histological analysis of human kidney samples revealed that high lipid levels induced the development of renal fibrosis. To elucidate the mechanism underlying lipid nephrotoxicity, we used two types of mouse models (Apoe−/− and C57BL/6 mice fed a 45 and 60% high-fat diet, respectively). Histological analysis of kidney tissues revealed high-lipid-induced renal fibrosis and inflammation; this was confirmed by examining fibrotic and inflammatory marker expression using Western blotting and real-time polymerase chain reaction. Oxidized low-density lipoprotein (OX-LDL) significantly induced the fibrotic response in HK-2 tubular epithelial cells. RNA-sequencing and Gene Ontology analysis of differentially expressed mRNAs in OX-LDL-treated HK-2 tubular epithelial cells and real-time PCR validation in Apoe−/− mice showed that the expression of thrombospondin-1 (THBS1) in the high-fat group was significantly higher than that of the other top known genes, along with significant overexpression of its receptor CD47. THBS1 knockdown cells verified its relation to OX-LDL-induced fibrosis and inflammation. Liquid chromatography tandem mass spectrometry and STRING functional protein association network analyses predicted that THBS1/CD47 modulated the interaction between γ-catenin and E-cadherin and was involved in epithelial–mesenchymal transition, which was supported by immunoprecipitation and immunohistochemistry. CD47 downregulation following transfection with small-hairpin RNA in OX-LDL-treated tubular epithelial cells and treatment with anti-CD47 antibody restored the expression of E-cadherin and attenuated renal injury, fibrosis, and inflammatory response in OX-LDL-treated cells and in type 2 diabetes mellitus. These findings indicate that CD47 may serve as a potential therapeutic target in long-term lipid-induced kidney injury.
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Affiliation(s)
- Li Gao
- State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China
| | - Ting-Ting Yang
- State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China
| | - Jun-Sheng Zhang
- Pathophysiology Department, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Hong-Xia Liu
- State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China
| | - Dong-Cheng Cai
- State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China
| | - Lin-Tao Wang
- State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China
| | - Jing Wang
- State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China
| | - Xin-Wei Li
- State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China
| | - Kun Gao
- State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China
| | - Su-Ya Zhang
- State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China
| | - Yu-Jia Cao
- State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China
| | - Xiao-Xia Ji
- State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China
| | - Miao-Miao Yang
- Pathophysiology Department, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, China.,Anhui Yizhiben Center for Judicial Expertise, Hefei, China
| | - Biao Han
- Pathophysiology Department, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, China.,Anhui Yizhiben Center for Judicial Expertise, Hefei, China
| | - Sheng Wang
- Center for Scientific Research of Anhui Medical University, Hefei, China
| | - Lu He
- State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China
| | - Xiao-Yan Nie
- State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China
| | - Dan-Mei Liu
- State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China
| | - Gang Meng
- Pathophysiology Department, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, China.,Anhui Yizhiben Center for Judicial Expertise, Hefei, China
| | - Chao-Yong He
- State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing, China
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Antiobesity Effect of a Novel Herbal Formulation LI85008F in High-Fat Diet-Induced Obese Mice. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:6612996. [PMID: 33628302 PMCID: PMC7886504 DOI: 10.1155/2021/6612996] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 01/15/2021] [Accepted: 01/30/2021] [Indexed: 11/26/2022]
Abstract
A variety of natural products have been explored for their antiobesity potential and widely used to develop dietary supplements for the prevention of weight gain from excess body fat. In an attempt to find a natural antiobesity agent, this study was designed to evaluate the antiobesity activity of a novel herbal formulation LI85008F composed of extracts from three medicinal plants in high-fat diet- (HFD-) induced obese mice. After the thirteen-week oral administration of the test materials to mice, the body weight gain, whole-body fat mass, adipose tissue weight, and the expression levels of obesity-related proteins were measured. Our results indicated that LI85008F can suppress body weight gain and lower whole-body fat mass in HFD-induced obese mice. Significant decreases in epididymal and retroperitoneal fat mass were observed in LI85008F-treated groups compared with the HFD-fed control group (p < 0.05). Furthermore, the oral administration of LI85008F caused significant decreases in the expression level of adipogenic (C/EBPα and PPARγ) and lipogenic (ACC) markers and notable increases in the production level of thermogenetic (AMPKα, PGC1α and UCP1) and lipolytic (HSL) proteins. These findings suggest that LI85008F holds great promise for a novel herbal formulation with antiobesity activities, preventing body fat accumulation and altering lipid metabolism.
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