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1
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Fan J, Hu J. Retinol binding protein 4 and type 2 diabetes: from insulin resistance to pancreatic β-cell function. Endocrine 2024; 85:1020-1034. [PMID: 38520616 DOI: 10.1007/s12020-024-03777-5] [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: 09/22/2023] [Accepted: 03/01/2024] [Indexed: 03/25/2024]
Abstract
BACKGROUND AND AIM Retinol binding protein 4 (RBP4) is an adipokine that has been explored as a key biomarker of type 2 diabetes mellitus (T2DM) in recent years. Researchers have conducted a series of experiments to understand the interplay between RBP4 and T2DM, including its role in insulin resistance and pancreatic β-cell function. The results of these studies indicate that RBP4 has a significant influence on T2DM and is considered a potential biomarker of T2DM. However, there have also been some controversies about the relationship between RBP4 levels and T2DM. In this review, we update and summarize recent studies focused on the relationship between RBP4 and T2DM and its role in insulin resistance and pancreatic β-cell function to clarify the existing controversy and provide evidence for future studies. We also assessed the potential therapeutic applications of RBP4 in treating T2DM. METHODS A narrative review. RESULTS Overall, there were significant associations between RBP4 levels, insulin resistance, pancreatic β-cell function, and T2DM. CONCLUSIONS More mechanistic studies are needed to determine the role of RBP4 in the onset of T2DM, especially in terms of pancreatic β-cell function. In addition, further studies are required to evaluate the effects of drug intervention, lifestyle intervention, and bariatric surgery on RBP4 levels to control T2DM and the role of reducing RBP4 levels in improving insulin sensitivity and pancreatic β-cell function.
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Affiliation(s)
- Jiahua Fan
- State Key Laboratory of Respiratory Disease, Guangzhou Key Laboratory of Tuberculosis Research, Department of Clinical Nutrition, Guangzhou Chest Hospital, Institute of Tuberculosis, Guangzhou Medical University, Guangzhou, 510095, Guangdong, PR China.
| | - Jinxing Hu
- State Key Laboratory of Respiratory Disease, Guangzhou Key Laboratory of Tuberculosis Research, Department of Tuberculosis, Guangzhou Chest Hospital, Institute of Tuberculosis, Guangzhou Medical University, Guangzhou, 510095, Guangdong, PR China
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Li JJ, Sa RL, Zhang Y, Yan ZL. Evaluating new biomarkers for diabetic nephropathy: Role of α2-macroglobulin, podocalyxin, α-L-fucosidase, retinol-binding protein-4, and cystatin C. World J Diabetes 2024; 15:1212-1225. [PMID: 38983807 PMCID: PMC11229980 DOI: 10.4239/wjd.v15.i6.1212] [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: 01/07/2024] [Revised: 02/27/2024] [Accepted: 04/30/2024] [Indexed: 06/11/2024] Open
Abstract
BACKGROUND The intricate relationship between type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) presents a challenge in understanding the significance of various biomarkers in diagnosis. AIM To elucidate the roles and diagnostic values of α2-macroglobulin (α2-MG), podocalyxin (PCX), α-L-fucosidase (AFU), retinol-binding protein-4 (RBP-4), and cystatin C (CysC) in DN. METHODS From December 2018 to December 2020, 203 T2DM patients were enrolled in the study. Of these, 115 were diagnosed with DN (115 patients), while the remaining 88 patients were classified as non-DN. The urinary levels of α2-MG, PCX, and AFU and the serum concentrations RBP-4 and CysC were measured in conjunction with other relevant clinical indicators to evaluate their potential correlations and diagnostic utility. RESULTS After adjustments for age and gender, significant positive correlations were observed between the biomarkers CysC, RBP-4, α2-MG/urinary creatinine (UCr), PCX/UCr, and AFU/UCr, and clinical indicators such as urinary albumin-to-creatinine ratio (UACR), serum creatinine, urea, 24-h total urine protein, and neutrophil-to-lymphocyte ratio (NLR). Conversely, these biomarkers exhibited negative correlations with the estimated glomerular filtration rate (P < 0.05). Receiver operating characteristic (ROC) curve analysis further demonstrated the diagnostic performance of these biomarkers, with UACR showcasing the highest area under the ROC curve (AUCROC) at 0.97. CONCLUSION This study underscores the diagnostic significance of α2-MG, PCX, and AFU in the development of DN. The biomarkers RBP-4, CysC, PCX, AFU, and α2-MG provide promising diagnostic insights, while UACR is the most potent diagnostic biomarker in assessing DN.
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Affiliation(s)
- Jing-Jing Li
- Department of Infectious Diseases, Inner Mongolia Medical University, Hohhot First Hospital, Hohhot 010000, Inner Mongolia Autonomous Region, China
| | - Ru-La Sa
- Department of Endocrinology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010000, Inner Mongolia Autonomous Region, China
| | - Yu Zhang
- Department of Dermatology, Inner Mongolia Autonomous Region People’s Hospital, Hohhot 010000, Inner Mongolia Autonomous Region, China
| | - Zhao-Li Yan
- Department of Endocrinology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010000, Inner Mongolia Autonomous Region, China
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Dong Z, Si G, Zhu X, Li C, Hua R, Teng J, Zhang W, Xu L, Qian W, Liu B, Wang J, Wang T, Tang Y, Zhao Y, Gong X, Tao Z, Xu Z, Li Y, Chen B, Kong X, Xu Y, Gu N, Li C. Diagnostic Performance and Safety of a Novel Ferumoxytol-Enhanced Coronary Magnetic Resonance Angiography. Circ Cardiovasc Imaging 2023; 16:580-590. [PMID: 37463240 DOI: 10.1161/circimaging.123.015404] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 06/13/2023] [Indexed: 07/20/2023]
Abstract
BACKGROUND Currently, noninvasive arteriography for the diagnosis of coronary artery disease is clinically limited to the computed tomography scanning, where patients have to be exposed to the radiation and risks associated with iodinated contrast. We aimed to investigate the diagnostic performance and safety of a novel ferumoxytol-enhanced coronary magnetic resonance angiography (CMRA) in patients with suspected coronary artery disease. METHODS Thirty patients, 19 males, with a median age of 63 years old, and 17 with renal insufficiency, who were scheduled for invasive coronary angiography, were enrolled. Ferumoxytol was administered intravenously with a dose of 3 mg/kg during CMRA. Images were acquired with an ECG-triggered, navigator-gated, inversion recovery-prepared 3D fast low-angle shot sequence, and the image quality was assessed by a 4-point scale. Eighteen-segment coronary artery model was adopted to evaluate the visibility of the coronary arteries, and the image quality and stenosis were evaluated in nine segments. The diagnostic performance of CMRA is described as sensitivity, specificity, positive and negative predictive values, and accuracy with the invasive coronary angiography results as reference. The patients' vital signs were monitored during CMRA, and their hepatic and renal functions were followed up for 3 months to evaluate the safety of ferumoxytol. RESULTS Two hundred fifty-two of the 270 study segments were identified by CMRA, and their quality score reached 3.6±0.7. Referring to the invasive coronary angiography results, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ferumoxytol-enhanced CMRA reached 100.0%, 66.7%, 92.3%, 100.0%, and 93.3% respectively in patient-based analysis; 91.4%, 90.9%, 86.5%, 94.3%, and 91.1%, respectively in vessel-based analysis; and 92.3%, 96.7%, 83.7%, 98.6%, and 96.0%, respectively in segment-based analysis. No ferumoxytol-related adverse event was observed during the 3-month follow-up. CONCLUSIONS Ferumoxytol-enhanced CMRA demonstrated good diagnostic performance and excellent safety in the diagnosis of significant coronary stenosis, providing an alternative to coronary computed tomography angiography for the diagnosis of coronary artery disease. REGISTRATION URL: https://www. CLINICALTRIALS gov; Unique identifier: NCT05032937.
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Affiliation(s)
- Zhou Dong
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (Z.D., C.L., R.H., J.T., W.Z., T.W., X.G., Z.T., Z.X., Y.L., B.C., X.K., C.L.)
| | - Guangxiang Si
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, Southeast University, Nanjing, China (G.S., N.G.)
| | - Xiaomei Zhu
- Department of Radiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (X.Z., L.X., W.Q., B.L., J.W., Y.X.)
| | - Chen Li
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (Z.D., C.L., R.H., J.T., W.Z., T.W., X.G., Z.T., Z.X., Y.L., B.C., X.K., C.L.)
| | - Rui Hua
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (Z.D., C.L., R.H., J.T., W.Z., T.W., X.G., Z.T., Z.X., Y.L., B.C., X.K., C.L.)
| | - Jianzhen Teng
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (Z.D., C.L., R.H., J.T., W.Z., T.W., X.G., Z.T., Z.X., Y.L., B.C., X.K., C.L.)
| | - Wenhao Zhang
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (Z.D., C.L., R.H., J.T., W.Z., T.W., X.G., Z.T., Z.X., Y.L., B.C., X.K., C.L.)
| | - Lulu Xu
- Department of Radiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (X.Z., L.X., W.Q., B.L., J.W., Y.X.)
| | - Wen Qian
- Department of Radiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (X.Z., L.X., W.Q., B.L., J.W., Y.X.)
| | - Bo Liu
- Department of Radiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (X.Z., L.X., W.Q., B.L., J.W., Y.X.)
| | - Jun Wang
- Department of Radiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (X.Z., L.X., W.Q., B.L., J.W., Y.X.)
| | - Tong Wang
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (Z.D., C.L., R.H., J.T., W.Z., T.W., X.G., Z.T., Z.X., Y.L., B.C., X.K., C.L.)
| | - Yingdan Tang
- Department of Biostatistics, School of Public Health, Nanjing Medical University, No. 101 Longmian Avenue, Nanjing, China (Y.T., Y.Z.)
| | - Yang Zhao
- Department of Biostatistics, School of Public Health, Nanjing Medical University, No. 101 Longmian Avenue, Nanjing, China (Y.T., Y.Z.)
| | - Xiaoxuan Gong
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (Z.D., C.L., R.H., J.T., W.Z., T.W., X.G., Z.T., Z.X., Y.L., B.C., X.K., C.L.)
| | - Zhiwen Tao
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (Z.D., C.L., R.H., J.T., W.Z., T.W., X.G., Z.T., Z.X., Y.L., B.C., X.K., C.L.)
| | - Zhihui Xu
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (Z.D., C.L., R.H., J.T., W.Z., T.W., X.G., Z.T., Z.X., Y.L., B.C., X.K., C.L.)
| | - Yong Li
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (Z.D., C.L., R.H., J.T., W.Z., T.W., X.G., Z.T., Z.X., Y.L., B.C., X.K., C.L.)
| | - Bo Chen
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (Z.D., C.L., R.H., J.T., W.Z., T.W., X.G., Z.T., Z.X., Y.L., B.C., X.K., C.L.)
| | - Xiangqing Kong
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (Z.D., C.L., R.H., J.T., W.Z., T.W., X.G., Z.T., Z.X., Y.L., B.C., X.K., C.L.)
| | - Yi Xu
- Department of Radiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (X.Z., L.X., W.Q., B.L., J.W., Y.X.)
| | - Ning Gu
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (Z.D., C.L., R.H., J.T., W.Z., T.W., X.G., Z.T., Z.X., Y.L., B.C., X.K., C.L.)
- Medical School, Nanjing University, Nanjing, Jiangsu, China (N.G.)
| | - Chunjian Li
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China (Z.D., C.L., R.H., J.T., W.Z., T.W., X.G., Z.T., Z.X., Y.L., B.C., X.K., C.L.)
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Schiborn C, Weber D, Grune T, Biemann R, Jäger S, Neu N, Müller von Blumencron M, Fritsche A, Weikert C, Schulze MB, Wittenbecher C. Retinol and Retinol Binding Protein 4 Levels and Cardiometabolic Disease Risk. Circ Res 2022; 131:637-649. [PMID: 36017698 PMCID: PMC9473720 DOI: 10.1161/circresaha.122.321295] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
BACKGROUND Despite mechanistic studies linking retinol and RBP4 (retinol binding protein 4) to the pathogenesis of cardiovascular diseases (CVD) and type 2 diabetes (T2D), epidemiological evidence is still conflicting. We investigated whether conflicting results of previous studies may be explained by differences in the association of retinol and RBP4 with cardiometabolic risk across subgroups with distinct sex, hypertension state, liver, or kidney function. METHODS We used case-cohorts nested in the EPIC (European Prospective Investigation Into Cancer and Nutrition)-Potsdam cohort (N=27 548) comprising a random sample of participants (n=2500) and all physician-verified cases of incident CVD (n=508, median follow-up time 8.2 years) and T2D (n=820, median follow-up time 6.3 years). We estimated nonlinear and linear multivariable-adjusted associations between the biomarkers and cardiometabolic diseases by restricted cubic splines and Cox regression, respectively, testing potential interactions with hypertension, liver, and kidney function. Additionally, we performed 2-sample Mendelian Randomization analyses in publicly available data. RESULTS The association of retinol with cardiometabolic risk was modified by hypertension state (P interaction CVD<0.001; P interaction T2D<0.001). Retinol was associated with lower cardiometabolic risk in participants with treated hypertension (hazard ratioper SD [95% CI]: CVD, 0.71 [0.56-0.90]; T2D, 0.81 [0.70-0.94]) but with higher cardiometabolic risk in normotensive participants (CVD, 1.32 [1.06-1.64]; T2D, 1.15 [0.98-1.36]). Our analyses also indicated a significant interaction between RBP4 and hypertension on CVD risk (P interaction=0.04). Regarding T2D risk, we observed a u-shaped association with RBP4 in women (P nonlinearity=0.01, P effect=0.02) and no statistically significant association in men. The biomarkers' interactions with liver or kidney function were not statistically significant. Hypertension state-specific associations for retinol concentrations with cardiovascular mortality risk were replicated in National Health and Nutrition Examination Survey III. CONCLUSIONS Our findings suggest a hypertension-dependent relationship between plasma retinol and cardiometabolic risk and complex interactions of RBP4 with sex and hypertension on cardiometabolic risk.
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Affiliation(s)
- Catarina Schiborn
- German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany (C.S., D.W., T.G., S.J., N.N., M.M.v.B., M.B.S., C. Wittenbecher).,German Center for Diabetes Research (DZD), Neuherberg, Germany (C.S., S.J., A.F., M.B.S., C. Wittenbecher)
| | - Daniela Weber
- German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany (C.S., D.W., T.G., S.J., N.N., M.M.v.B., M.B.S., C. Wittenbecher)
| | - Tilman Grune
- German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany (C.S., D.W., T.G., S.J., N.N., M.M.v.B., M.B.S., C. Wittenbecher).,German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Germany (T.G.)
| | - Ronald Biemann
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Germany (R.B.)
| | - Susanne Jäger
- German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany (C.S., D.W., T.G., S.J., N.N., M.M.v.B., M.B.S., C. Wittenbecher).,German Center for Diabetes Research (DZD), Neuherberg, Germany (C.S., S.J., A.F., M.B.S., C. Wittenbecher)
| | - Natascha Neu
- German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany (C.S., D.W., T.G., S.J., N.N., M.M.v.B., M.B.S., C. Wittenbecher)
| | - Marie Müller von Blumencron
- German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany (C.S., D.W., T.G., S.J., N.N., M.M.v.B., M.B.S., C. Wittenbecher)
| | - Andreas Fritsche
- German Center for Diabetes Research (DZD), Neuherberg, Germany (C.S., S.J., A.F., M.B.S., C. Wittenbecher).,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Germany (A.F.).,Division of Endocrinology, Diabetology and Nephrology, Department of Internal Medicine, University of Tübingen, Germany (A.F.)
| | - Cornelia Weikert
- Department of Food Safety, German Federal Institute for Risk Assessment, Berlin, Germany (C. Weikert)
| | - Matthias B. Schulze
- German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany (C.S., D.W., T.G., S.J., N.N., M.M.v.B., M.B.S., C. Wittenbecher).,German Center for Diabetes Research (DZD), Neuherberg, Germany (C.S., S.J., A.F., M.B.S., C. Wittenbecher).,Department of Food Safety, German Federal Institute for Risk Assessment, Berlin, Germany (C. Weikert)
| | - Clemens Wittenbecher
- German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany (C.S., D.W., T.G., S.J., N.N., M.M.v.B., M.B.S., C. Wittenbecher).,German Center for Diabetes Research (DZD), Neuherberg, Germany (C.S., S.J., A.F., M.B.S., C. Wittenbecher).,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (C. Wittenbecher).,Division of Food and Nutrition Science, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden (C. Wittenbecher)
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Berger MM, Shenkin A, Schweinlin A, Amrein K, Augsburger M, Biesalski HK, Bischoff SC, Casaer MP, Gundogan K, Lepp HL, de Man AME, Muscogiuri G, Pietka M, Pironi L, Rezzi S, Cuerda C. ESPEN micronutrient guideline. Clin Nutr 2022; 41:1357-1424. [PMID: 35365361 DOI: 10.1016/j.clnu.2022.02.015] [Citation(s) in RCA: 287] [Impact Index Per Article: 95.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 02/16/2022] [Indexed: 11/19/2022]
Abstract
BACKGROUND Trace elements and vitamins, named together micronutrients (MNs), are essential for human metabolism. Recent research has shown the importance of MNs in common pathologies, with significant deficiencies impacting the outcome. OBJECTIVE This guideline aims to provide information for daily clinical nutrition practice regarding assessment of MN status, monitoring, and prescription. It proposes a consensus terminology, since many words are used imprecisely, resulting in confusion. This is particularly true for the words "deficiency", "repletion", "complement", and "supplement". METHODS The expert group attempted to apply the 2015 standard operating procedures (SOP) for ESPEN which focuses on disease. However, this approach could not be applied due to the multiple diseases requiring clinical nutrition resulting in one text for each MN, rather than for diseases. An extensive search of the literature was conducted in the databases Medline, PubMed, Cochrane, Google Scholar, and CINAHL. The search focused on physiological data, historical evidence (published before PubMed release in 1996), and observational and/or randomized trials. For each MN, the main functions, optimal analytical methods, impact of inflammation, potential toxicity, and provision during enteral or parenteral nutrition were addressed. The SOP wording was applied for strength of recommendations. RESULTS There was a limited number of interventional trials, preventing meta-analysis and leading to a low level of evidence. The recommendations underwent a consensus process, which resulted in a percentage of agreement (%): strong consensus required of >90% of votes. Altogether the guideline proposes sets of recommendations for 26 MNs, resulting in 170 single recommendations. Critical MNs were identified with deficiencies being present in numerous acute and chronic diseases. Monitoring and management strategies are proposed. CONCLUSION This guideline should enable addressing suboptimal and deficient status of a bundle of MNs in at-risk diseases. In particular, it offers practical advice on MN provision and monitoring during nutritional support.
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Affiliation(s)
- Mette M Berger
- Department of Adult Intensive Care, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
| | - Alan Shenkin
- Institute of Aging and Chronic Disease, University of Liverpool, Liverpool, UK.
| | - Anna Schweinlin
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Karin Amrein
- Medical University of Graz, Department of Internal Medicine, Division of Endocrinology and Diabetology, Austria.
| | - Marc Augsburger
- University Centre of Legal Medicine Lausanne-Geneva, Lausanne University Hospital and University of Lausanne, Geneva University Hospital and University of Geneva, Lausanne-Geneva, Switzerland.
| | | | - Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Michael P Casaer
- KU Leuven, Department of Cellular and Molecular Medicine, Laboratory of Intensive Care Medicine, Leuven, Belgium.
| | - Kursat Gundogan
- Division of Intensive Care Medicine, Department of Internal Medicine, Erciyes University School of Medicine, Kayseri, Turkey.
| | | | - Angélique M E de Man
- Department of Intensive Care Medicine, Research VUmc Intensive Care (REVIVE), Amsterdam Cardiovascular Science (ACS), Amsterdam Infection and Immunity Institute (AI&II), Amsterdam Medical Data Science (AMDS), Amsterdam UMC, Location VUmc, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands.
| | - Giovanna Muscogiuri
- Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università di Napoli (Federico II), Naples, Italy; United Nations Educational, Scientific and Cultural Organization (UNESCO) Chair for Health Education and Sustainable Development, Federico II, University, Naples, Italy.
| | - Magdalena Pietka
- Pharmacy Department, Stanley Dudrick's Memorial Hospital, Skawina, Poland.
| | - Loris Pironi
- Alma Mater Studiorum - University of Bologna, Department of Medical and Surgical Sciences, Italy; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Centre for Chronic Intestinal Failure - Clinical Nutrition and Metabolism Unit, Italy.
| | - Serge Rezzi
- Swiss Nutrition and Health Foundation (SNHf), Epalinges, Switzerland.
| | - Cristina Cuerda
- Departamento de Medicina, Universidad Complutense de Madrid, Nutrition Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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Isotope-dilution liquid chromatography-tandem mass spectrometry for quantification of human retinol binding protein 4 in serum. Anal Biochem 2022; 645:114589. [DOI: 10.1016/j.ab.2022.114589] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Revised: 01/31/2022] [Accepted: 02/01/2022] [Indexed: 01/15/2023]
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Wu P, Wang Y, Ye Y, Yang X, Lu Q, Liu Y, Zeng H, Song X, Yan S, Wen Y, Qi X, Yang CX, Liu G, Lv C, Pan XF, Pan A. Serum retinol-binding protein 4 levels and risk of gestational diabetes mellitus: A nested case-control study in Chinese women and an updated meta-analysis. Diabetes Metab Res Rev 2022; 38:e3496. [PMID: 34537998 DOI: 10.1002/dmrr.3496] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Revised: 07/25/2021] [Accepted: 08/11/2021] [Indexed: 11/11/2022]
Abstract
AIMS We prospectively evaluated the association of circulating retinol-binding protein 4 (RBP4) levels in early pregnancy and risk of incident gestational diabetes mellitus (GDM) in pregnant women. METHODS A nested case-control study was conducted among 332 women who developed GDM and 664 matched controls based on the Tongji-Shuangliu Birth Cohort. GDM was diagnosed during 24-28 weeks of gestation according to the International Association of Diabetes and Pregnancy Study Group criteria. Serum RBP4 levels in early pregnancy (6-15 weeks of gestation) were determined by ELISA assay. Multivariable conditional logistic regression models were used to analyse the association and generated the odds ratio (OR) and 95% confidence interval (CI). EMBASE and PubMed were searched up to 30 November 2020 to identify studies investigating the association between blood RBP4 levels in early pregnancy and incident GDM. RESULTS In the multivariable model with adjustment of potential risk factors, the OR comparing the extreme quartiles of serum RBP4 levels was 2.26 (95% CI: 1.34, 3.81; p for trend <0.001), and each standard deviation (SD) increment of RBP4 was associated with 1.39-fold (95% CI: 1.15, 1.69) higher risk of GDM. The results were confirmed in a meta-analysis that included additional four studies with an overall OR of 1.47 (95% CI: 1.18, 1.83) per 1-SD increment of RBP4. CONCLUSIONS Serum RBP4 levels in early pregnancy, independent of metabolic risk factors, are positively associated with the risk of GDM in pregnant women. Our findings may provide new insights into the mechanisms underlying the aetiology of GDM.
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Affiliation(s)
- Ping Wu
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yi Wang
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yi Ye
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xue Yang
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Qi Lu
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yan Liu
- Department of Obstetrics and Gynecology, Shuangliu Maternal and Child Health Hospital, Chengdu, Sichuan, China
| | - Huayan Zeng
- Nutrition Department, Shuangliu Maternal and Child Health Hospital, Chengdu, Sichuan, China
| | - Xingyue Song
- Department of Emergency, Hainan Clinical Research Center for Acute and Critical Diseases, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
| | - Shijiao Yan
- Research Unit of Island Emergency Medicine, Chinese Academy of Medical Sciences, Hainan Medical University, Haikou, Hainan, China
- School of Public Health, Hainan Medical University, Haikou, Hainan, China
| | - Ying Wen
- Department of Communicable Diseases Control and Prevention, Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China
| | - Xiaorong Qi
- Department of Gynecology and Obstetrics, West China Second Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan, China
| | - Chun-Xia Yang
- Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Gang Liu
- Department of Nutrition & Food Hygiene, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Chuanzhu Lv
- Research Unit of Island Emergency Medicine, Chinese Academy of Medical Sciences, Hainan Medical University, Haikou, Hainan, China
- Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Medical University, Haikou, Hainan, China
- Emergency Medicine Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Xiong-Fei Pan
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - An Pan
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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Krieg L, Schaffert A, Kern M, Landgraf K, Wabitsch M, Beck-Sickinger AG, Körner A, Blüher M, von Bergen M, Schubert K. An MRM-Based Multiplexed Quantification Assay for Human Adipokines and Apolipoproteins. Molecules 2020; 25:molecules25040775. [PMID: 32054032 PMCID: PMC7070386 DOI: 10.3390/molecules25040775] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 02/06/2020] [Accepted: 02/08/2020] [Indexed: 12/14/2022] Open
Abstract
Adipokines and apolipoproteins are key regulators and potential biomarkers in obesity and associated diseases and their quantitative assessment is crucial for functional analyses to understand disease mechanisms. Compared to routinely used ELISAs, multiple reaction monitoring (MRM)-based mass spectrometry allows multiplexing and detection of proteins for which antibodies are not available. Thus, we established an MRM method to quantify 9 adipokines and 10 apolipoproteins in human serum. We optimized sample preparation by depleting the two most abundant serum proteins for improved detectability of low abundant proteins. Intra-day and inter-day imprecision were below 16.5%, demonstrating a high accuracy. In 50 serum samples from participants with either normal weight or obesity, we quantified 8 adipokines and 10 apolipoproteins. Significantly different abundances were observed for five adipokines (adipsin, adiponectin, chemerin, leptin, vaspin) and four apolipoproteins (apo-B100/-C2/-C4/-D) between the body mass index (BMI) groups. Additionally, we applied our MRM assay to serum samples from normal weight children and human adipocyte cell culture supernatants to proof the feasibility for large cohort studies and distinct biological matrices. In summary, this multiplexed assay facilitated the investigation of relationships between adipokines or apolipoproteins and phenotypes or clinical parameters in large cohorts, which may contribute to disease prediction approaches in the future.
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Affiliation(s)
- Laura Krieg
- Department of Molecular Systems Biology, UFZ, Helmholtz-Centre for Environmental Research, Permoserstraße 15, 04318 Leipzig, Germany; (L.K.)
| | - Alexandra Schaffert
- Department of Molecular Systems Biology, UFZ, Helmholtz-Centre for Environmental Research, Permoserstraße 15, 04318 Leipzig, Germany; (L.K.)
| | - Matthias Kern
- Department of Medicine, University of Leipzig, Liebigstraße 27b, 04103 Leipzig, Germany
| | - Kathrin Landgraf
- Center for Pediatric Research, Hospital for Children & Adolescents, University of Leipzig, Liebigstraße 20a, 04103 Leipzig, Germany
| | - Martin Wabitsch
- Division of Pediatric Endocrinology Diabetes, Ulm University Medical Center, Eythstraße 24 89075 Ulm, Germany
| | | | - Antje Körner
- Center for Pediatric Research, Hospital for Children & Adolescents, University of Leipzig, Liebigstraße 20a, 04103 Leipzig, Germany
| | - Matthias Blüher
- Department of Medicine, University of Leipzig, Liebigstraße 27b, 04103 Leipzig, Germany
| | - Martin von Bergen
- Department of Molecular Systems Biology, UFZ, Helmholtz-Centre for Environmental Research, Permoserstraße 15, 04318 Leipzig, Germany; (L.K.)
- Institute of Biochemistry, University of Leipzig, Brüderstraße 34, 04103 Leipzig, Germany
| | - Kristin Schubert
- Department of Molecular Systems Biology, UFZ, Helmholtz-Centre for Environmental Research, Permoserstraße 15, 04318 Leipzig, Germany; (L.K.)
- Correspondence:
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9
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Liu C, Che Y. Retinol-Binding Protein 4 Predicts Lesion Volume (Determined by MRI) and Severity of Acute Ischemic Stroke. Neurotox Res 2018; 35:92-99. [PMID: 30030781 DOI: 10.1007/s12640-018-9933-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 06/24/2018] [Accepted: 07/11/2018] [Indexed: 12/25/2022]
Abstract
Retinol-binding protein 4 (RBP4) is an adipocyte-secreted molecule and is associated with cardiovascular risk factors. The aim of this study was to assess the clinical significance of serum levels of RBP4 in Chinese patients with acute ischemic stroke (AIS). We sequentially screened patients with first-ever AIS who were admitted to our Hospital between September 2016 and October 2017. Serum levels of RBP4 were assayed with solid-phase sandwich ELISA, and severity of stroke was evaluated with the National Institutes of Health Stroke Scale (NIHSS) score on admission. We used logistic regression models to assess the relationship between RBP4 levels and stroke risk and severity. During the inclusion period, 323 patients completed the study. Our results indicated that the median serum RBP4 levels were significantly (P < 0.001) higher in patients with AIS than in those normal cases [28.9 (IQR, 17.3-39.6) μg/ml vs. 23.7 (14.6-32.3) μg/ml]. In logistic regression analysis, for each 1 unit increase of serum level of RBP4, the unadjusted and adjusted risks of AIS increased by 4% (OR 1.04 [95% CI 1.02-1.05], P < 0.001) and 3% (1.03 [1.01-1.04], P < 0.001), respectively. At admission, 116 patients (35.9%) had a minor stroke (NIHSS < 6). In logistic regression analysis, for each 1 unit increase of serum level of RBP4, the unadjusted and adjusted risks of moderate-to-high stroke increased by 7% (OR 1.07 [95% CI 1.05-1.09], P < 0.001) and 5% (1.05 [1.02-1.07], P < 0.001), respectively. Elevated levels of RBP4 could be considered an independent diagnosis marker of AIS. Elevated levels of RBP4 were significantly associated with higher stroke severity in Chinese sample.
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Affiliation(s)
- Chao Liu
- Department of CT Diagnosis, Cangzhou Central Hospital, No. 16, Xinhua West Road, Cangzhou, 061001, China
| | - Yanxu Che
- Department of CT Diagnosis, Cangzhou Central Hospital, No. 16, Xinhua West Road, Cangzhou, 061001, China.
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Noor R, Rini EA, Yerizel E. Retinol binding protein 4, obesity, and insulin resistance in adolescents. PAEDIATRICA INDONESIANA 2017. [DOI: 10.14238/pi57.1.2017.1-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Background Obesity is a global problem. Even in poor and developing countries, obesity has reached alarming levels. In childhood, obesity may lead to insulin resistance. Retinol binding protein (RBP4), secreted primarily by liver and adipose tissues, was recently proposed as a link between obesity and insulin resistance. The role of RBP4 in pediatric obesity and its relationship with insulin resistance have not been well elucidated.Objective To compare RBP4 levels in obese and lean adolescents and to assess for a relationship between RBP4 levels and insulin resistance. Method This cross-sectional study was conducted in three senior high schools in Padang, West Sumatera, Indonesia. Subjects were adolescents aged 14-18 years, who were obese or normal weight (n=56). We measured subjects’ body mass index (BMI) and serum RBP4 concentrations. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR) index.Results Similar RBP4 levels were found in the obese and normoweight groups (P>0.05). Higher RBP4 levels were found in the insulin resistant compared to the non-insulin resistant group, but the difference was not significant (P > 0.05).Conclusion There is no significant difference in mean RBP4 levels in obese adolescents compared to normoweight adolescents. Nor are mean RBP4 levels significantly different between obese adolescents with and without insulin resistance.
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11
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Mass spectrometric immunoassays for discovery, screening and quantification of clinically relevant proteoforms. Bioanalysis 2016; 8:1623-1633. [PMID: 27396364 DOI: 10.4155/bio-2016-0060] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Human proteins can exist as multiple proteoforms with potential diagnostic or prognostic significance. MS top-down approaches are ideally suited for proteoforms identification because there is no prerequisite for a priori knowledge of the specific proteoform. One such top-down approach, termed mass spectrometric immunoassay utilizes antibody-derivatized microcolumns for rapid and contained proteoforms isolation and detection via MALDI-TOF MS. The mass spectrometric immunoassay can also provide quantitative measurement of the proteoforms through inclusion of an internal reference standard into the analytical sample, serving as normalizer for all sample processing and data acquisition steps. Reviewed here are recent developments and results from the application of mass spectrometric immunoassays for discovery of clinical correlations of specific proteoforms for the protein biomarkers RANTES, retinol binding protein, serum amyloid A and apolipoprotein C-III.
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12
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Mahfouz MH, Assiri AM, Mukhtar MH. Assessment of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Retinol-Binding Protein 4 (RBP4) in Type 2 Diabetic Patients with Nephropathy. Biomark Insights 2016; 11:31-40. [PMID: 26917947 PMCID: PMC4756860 DOI: 10.4137/bmi.s33191] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Revised: 11/25/2015] [Accepted: 11/27/2015] [Indexed: 12/15/2022] Open
Abstract
Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes. The study aims to evaluate the diagnostic value of serum neutrophil gelatinase-associated lipocalin (NGAL) and retinol-binding protein 4 (RBP4) as biomarkers for early detection of nephropathy in type 2 diabetic patients. The current study was performed on 150 type 2 diabetic patients. These patients were classified into three equal groups according to their albumin/creatinine ratio (ACR), including patients with normoalbuminuria (ACR <30 mg/g creatinine), patients with microalbuminuria (ACR = 30-300 mg/g creatinine), and patients with macroalbuminuria (ACR >300 mg/g creatinine). Fifty apparently healthy subjects matching the same age and socioeconomic status with diabetic subjects were selected as a control group. The plasma glucose, insulin, glycosylated hemoglobin (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, urea, creatinine, cystatin C, glomerular filtration rate (GFR), NGAL, and RBP4 were measured in the studied groups. Significantly elevated NGAL and RBP4 levels were observed in micro- and macroalbuminuric diabetic groups when compared to the control and normoalbuminuric diabetic groups. NGAL and RBP4 were found to correlate positively with duration of diabetes, systolic and diastolic blood pressure, glucose, HbA1c, HOMA-IR, triacylglycerol, and ACR, but correlate inversely with GFR in DN groups. Receiver operating characteristic curves revealed that for early detection of DN, the best cutoff values to discriminate DN and diabetic without nephropathy groups were 91.5 ng/mL for NGAL with 87% sensitivity, 74% specificity, and area under the curve (AUC) = 0.881; 24.5 ng/mL for RBP4 with 84% sensitivity, 90% specificity, and AUC = 0.912; and 37.5 mg/g creatinine for ACR with 89% sensitivity, 72% specificity, and AUC = 0.819. RBP4 is more specific (90% specificity) than NGAL (74% specificity) and ACR (72% specificity). Therefore, RBP4 marker may serve as a tool to follow-up clinical monitoring of the development and progression of DN.
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Affiliation(s)
- Mohamed H. Mahfouz
- Biochemistry Unit, Research Centre for Medicine and Medical Sciences, Deanship of Scientific Research (DSR), Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia (KSA)
| | - Adel M. Assiri
- Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia (KSA)
| | - Mohammed H. Mukhtar
- Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia (KSA)
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13
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Chemerin in renal dysfunction and cardiovascular disease. Vascul Pharmacol 2016; 77:28-34. [DOI: 10.1016/j.vph.2015.10.007] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Accepted: 10/31/2015] [Indexed: 01/08/2023]
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Shao B, de Boer I, Tang C, Mayer PS, Zelnick L, Afkarian M, Heinecke JW, Himmelfarb J. A Cluster of Proteins Implicated in Kidney Disease Is Increased in High-Density Lipoprotein Isolated from Hemodialysis Subjects. J Proteome Res 2015; 14:2792-806. [PMID: 26011469 DOI: 10.1021/acs.jproteome.5b00060] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Cardiovascular disease is the leading cause of death in end-stage renal disease (ESRD) patients treated with hemodialysis. An important contributor might be a decline in the cardioprotective effects of high-density lipoprotein (HDL). One important factor affecting HDL's cardioprotective properties may involve the alterations of protein composition in HDL. In the current study, we used complementary proteomics approaches to detect and quantify relative levels of proteins in HDL isolated from control and ESRD subjects. Shotgun proteomics analysis of HDL isolated from 20 control and 40 ESRD subjects identified 63 proteins in HDL. Targeted quantitative proteomics by isotope-dilution selective reaction monitoring revealed that 22 proteins were significantly enriched and 6 proteins were significantly decreased in ESRD patients. Strikingly, six proteins implicated in renal disease, including B2M, CST3, and PTGDS, were markedly increased in HDL of uremic subjects. Moreover, several of these proteins (SAA1, apoC-III, PON1, etc.) have been associated with atherosclerosis. Our observations indicate that the HDL proteome is extensively remodeled in uremic subjects. Alterations of the protein cargo of HDL might impact HDL's proposed cardioprotective properties. Quantifying proteins in HDL may be useful in the assessment of cardiovascular risk in patients with ESRD and in assessing response to therapeutic interventions.
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Affiliation(s)
- Baohai Shao
- †Diabetes and Obesity Center of Excellence and ‡Kidney Research Institute, Department of Medicine, University of Washington, 850 Republican Street, Seattle, Washington 98195, United States
| | - Ian de Boer
- †Diabetes and Obesity Center of Excellence and ‡Kidney Research Institute, Department of Medicine, University of Washington, 850 Republican Street, Seattle, Washington 98195, United States
| | - Chongren Tang
- †Diabetes and Obesity Center of Excellence and ‡Kidney Research Institute, Department of Medicine, University of Washington, 850 Republican Street, Seattle, Washington 98195, United States
| | - Philip S Mayer
- †Diabetes and Obesity Center of Excellence and ‡Kidney Research Institute, Department of Medicine, University of Washington, 850 Republican Street, Seattle, Washington 98195, United States
| | - Leila Zelnick
- †Diabetes and Obesity Center of Excellence and ‡Kidney Research Institute, Department of Medicine, University of Washington, 850 Republican Street, Seattle, Washington 98195, United States
| | - Maryam Afkarian
- †Diabetes and Obesity Center of Excellence and ‡Kidney Research Institute, Department of Medicine, University of Washington, 850 Republican Street, Seattle, Washington 98195, United States
| | - Jay W Heinecke
- †Diabetes and Obesity Center of Excellence and ‡Kidney Research Institute, Department of Medicine, University of Washington, 850 Republican Street, Seattle, Washington 98195, United States
| | - Jonathan Himmelfarb
- †Diabetes and Obesity Center of Excellence and ‡Kidney Research Institute, Department of Medicine, University of Washington, 850 Republican Street, Seattle, Washington 98195, United States
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Wurst U, Ebert T, Kralisch S, Stumvoll M, Fasshauer M. Serum levels of the adipokine Pref-1 in gestational diabetes mellitus. Cytokine 2015; 71:161-4. [DOI: 10.1016/j.cyto.2014.10.015] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2013] [Revised: 08/11/2014] [Accepted: 10/28/2014] [Indexed: 01/15/2023]
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Ansar H, Mirzaei K, Malek A, Najmafshar A, Hossein-nezhad A. Possible resting metabolic rate modification by the circulating RBP4 in obese subjects. Diabetes Metab Syndr 2015; 9:19-23. [PMID: 25450816 DOI: 10.1016/j.dsx.2014.09.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
AIM Adipose tissue derived retinol-binding protein 4 (RBP-4), known as one of the most important adipokins, has a link with insulin resistance and metabolic syndrome in obesity. The purpose of this study was to investigate the possible correlation between fasting serum RBP4 and resting metabolic rate (RMR) as a predictor of weight gain, body composition and insulin resistance in obese and non-obese subjects. MATERIALS AND METHODS In this case-control study, 73 obese and 90 non-obese participants were assessed following an overnight fasting for RMR by means of indirect calorimetry. Body composition was measured using body composition analyzer. Serum RBP4 levels were quantified by ELISA method. RESULTS Circulating RBP4 level correlated positively with log insulin (r=0.278, p=0.04) in obese subjects. There were no significant correlation between RBP4 and body composition in obese subjects except fat free mass (r=0.42, p=0.001). We found reduced RMR/kg in higher RBP4 concentration, moreover, a negative correlation was found between RBP4 and RMR/kg (r=-0.35, p=0.01) in obese group. Based on ROC analysis and RMR/kg cut-off value (=20 kcal/24 h/kg) for predicting the risk of obesity, 83.3% of participants with RMR/kg<20 kcal/24 h/kg had high RBP4 concentration, however in subjects with RMR/kg≥20 kcal/24 h/kg this percentage was 16.7 (p=0.01). CONCLUSION Our findings demonstrated that RBP4 concentration had relation with RMR which was different among obese and non-obese groups. These results may suggest the possible role of RBP4 in alteration of metabolic rate through insulin or other metabolic effects.
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Affiliation(s)
- Hasti Ansar
- School of Nutritional Science and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Khadijeh Mirzaei
- School of Nutritional Science and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Anita Malek
- Department of Pathology and Laboratory Medicine, Boston Medical Center, Boston, MA, USA
| | | | - Arash Hossein-nezhad
- Tehran University of Medical Science, Tehran, Iran; Department of Medicine, Section of Endocrinology, Nutrition and Diabetes, Vitamin D, Skin and Bone, Research Laboratory, Boston University Medical Center, Boston, MA, USA.
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Gursoy AY, Aynaoglu G, Caglar GS, Soylemez F. Early second trimester retinol-binding protein-4 values in cases with or without gestational diabetes mellitus risk factors: a cross-sectional study. J Obstet Gynaecol Res 2014; 41:55-61. [PMID: 25227411 DOI: 10.1111/jog.12499] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2013] [Accepted: 05/07/2014] [Indexed: 01/15/2023]
Abstract
AIM Retinol-binding protein-4 (RBP-4) has been correlated with different degrees of insulin resistance including gestational diabetes mellitus (GDM). Presence of risk factors for GDM is an indication for early screening. We studied RBP-4 values in the early second trimester of pregnancy in pregnant subjects with or without GDM risk factors and compared the results by routine GDM screening methodology. METHODS Seventy-nine patients with at least one GDM risk factor and 46 patients without any GDM risk factors were enrolled in the cross-sectional study as risk and control groups, respectively. In the early second trimester, RBP-4 values were measured, in addition to fasting plasma glucose and 50-g glucose challenge test in all subjects. RESULTS The RBP-4 values in 16-18th weeks of pregnancy were not significantly different between risk and control groups (95.3 ± 20.1 vs 103.1 ± 24.4 μg/mL, respectively; P = 0.055) although fasting plasma glucose levels and 50-g glucose challenge test results were higher in the risk group than the control group (75.3 vs 69.3 mg/dL and 112.4 vs 97.5 mg/dL, respectively; P < 0.05). CONCLUSION Presence of GDM risk factors does not have an impact on early second trimester RBP-4 values in pregnant subjects.
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Affiliation(s)
- Asli Yarci Gursoy
- Faculty of Medicine, Department of Obstetrics and Gynecology, Ufuk University, Ankara, Turkey
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Pelletier CC, Koppe L, Alix PM, Kalbacher E, Croze ML, Hadj-Aissa A, Fouque D, Guebre-Egziabher F, Soulage CO. The relationship between renal function and plasma concentration of the cachectic factor zinc-alpha2-glycoprotein (ZAG) in adult patients with chronic kidney disease. PLoS One 2014; 9:e103475. [PMID: 25076420 PMCID: PMC4116200 DOI: 10.1371/journal.pone.0103475] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2013] [Accepted: 07/02/2014] [Indexed: 12/04/2022] Open
Abstract
Zinc-α2-glycoprotein (ZAG), a potent cachectic factor, is increased in patients undergoing maintenance dialysis. However, there is no data for patients before initiation of renal replacement therapy. The purpose of the present study was to assess the relationship between plasma ZAG concentration and renal function in patients with a large range of glomerular filtration rate (GFR). Plasma ZAG concentration and its relationship to GFR were investigated in 71 patients with a chronic kidney disease (CKD) stage 1 to 5, 17 chronic hemodialysis (HD), 8 peritoneal dialysis (PD) and 18 non-CKD patients. Plasma ZAG concentration was 2.3-fold higher in CKD stage 5 patients and 3-fold higher in HD and PD patients compared to non-CKD controls (P<0.01). The hemodialysis session further increased plasma ZAG concentration (+39%, P<0.01). An inverse relationship was found between ZAG levels and plasma protein (rs = −0.284; P<0.01), albumin (rs = −0.282, P<0.05), hemoglobin (rs = −0.267, P<0.05) and HDL-cholesterol (rs = −0.264, P<0.05) and a positive correlation were seen with plasma urea (rs = 0.283; P<0.01). In multiple regression analyses, plasma urea and HDL-cholesterol were the only variables associated with plasma ZAG (r2 = 0.406, P<0.001). In CKD-5 patients, plasma accumulation of ZAG was not correlated with protein energy wasting. Further prospective studies are however needed to better elucidate the potential role of ZAG in end-stage renal disease.
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Affiliation(s)
- Caroline C. Pelletier
- Université de Lyon, F-69600, Oullins, France
- INSERM, U1060, CarMeN, INSA-Lyon, Univ. Lyon-1, Villeurbanne, France
- Hospices Civils de Lyon, Service de Néphrologie, Hôpital E Herriot, Lyon, France
| | - Laetitia Koppe
- Université de Lyon, F-69600, Oullins, France
- INSERM, U1060, CarMeN, INSA-Lyon, Univ. Lyon-1, Villeurbanne, France
- Hospices Civils de Lyon, Service de Néphrologie, Hôpital E Herriot, Lyon, France
| | - Pascaline M. Alix
- Université de Lyon, F-69600, Oullins, France
- INSERM, U1060, CarMeN, INSA-Lyon, Univ. Lyon-1, Villeurbanne, France
- Hospices Civils de Lyon, Service de Néphrologie, Hôpital E Herriot, Lyon, France
| | - Emilie Kalbacher
- Université de Lyon, F-69600, Oullins, France
- INSERM, U1060, CarMeN, INSA-Lyon, Univ. Lyon-1, Villeurbanne, France
- Hospices Civils de Lyon, Service de Néphrologie, Hôpital E Herriot, Lyon, France
| | - Marine L. Croze
- Université de Lyon, F-69600, Oullins, France
- INSERM, U1060, CarMeN, INSA-Lyon, Univ. Lyon-1, Villeurbanne, France
| | - Aoumeur Hadj-Aissa
- Université de Lyon, F-69600, Oullins, France
- Hospices Civils de Lyon, Exploration Fonctionnelle Rénale et Métabolique, Hôpital E Herriot, Lyon, France
| | - Denis Fouque
- Université de Lyon, F-69600, Oullins, France
- INSERM, U1060, CarMeN, INSA-Lyon, Univ. Lyon-1, Villeurbanne, France
- Hospices Civils de Lyon, Service de Néphrologie, Centre Hospitalier Lyon-SUD, Pierre-Bénite, France
| | - Fitsum Guebre-Egziabher
- Université de Lyon, F-69600, Oullins, France
- INSERM, U1060, CarMeN, INSA-Lyon, Univ. Lyon-1, Villeurbanne, France
- Hospices Civils de Lyon, Service de Néphrologie, Hôpital E Herriot, Lyon, France
| | - Christophe O. Soulage
- Université de Lyon, F-69600, Oullins, France
- INSERM, U1060, CarMeN, INSA-Lyon, Univ. Lyon-1, Villeurbanne, France
- * E-mail:
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Ebert T, Focke D, Petroff D, Wurst U, Richter J, Bachmann A, Lössner U, Kralisch S, Kratzsch J, Beige J, Bast I, Anders M, Blüher M, Stumvoll M, Fasshauer M. Serum levels of the myokine irisin in relation to metabolic and renal function. Eur J Endocrinol 2014; 170:501-6. [PMID: 24399249 DOI: 10.1530/eje-13-1053] [Citation(s) in RCA: 93] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVE Irisin has recently been introduced as a novel myokine which reverses visceral obesity and improves glucose metabolism in mice. However, regulation of irisin in humans in relation to renal and metabolic disease has not been comprehensively studied. DESIGN AND METHODS Serum irisin levels were quantified by ELISA and correlated with anthropometric and biochemical parameters of renal function, glucose and lipid metabolism, as well as inflammation, in 532 patients with stages 1-5 of chronic kidney disease (CKD). RESULTS Median serum irisin levels adjusted for age, gender, and BMI significantly decreased with increasing CKD stage and lowest concentrations were seen in patients with CKD stage 5. Furthermore, irisin concentrations were associated with facets of the metabolic syndrome including diastolic blood pressure, markers of impaired glucose tolerance, and dyslipidemia in univariate analysis. Moreover, markers of renal function, e.g. glomerular filtration rate, and insulin resistance, e.g. homeostasis model assessment of insulin resistance, remained independently associated with circulating irisin levels in robust multivariate analysis. CONCLUSIONS We show that irisin serum concentrations decrease with increasing CKD stage and are independently and positively predicted by renal function and insulin resistance. The physiological relevance of our findings, as well as the factors contributing to irisin regulation in humans, needs to be further defined in future experiments.
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Affiliation(s)
- Thomas Ebert
- Department of Endocrinology and Nephrology, University of Leipzig, Liebigstraße 20, 04103 Leipzig, Germany
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Molfino A, Heymsfield SB, Zhu F, Kotanko P, Levin NW, Dwyer T, Kaysen GA. Prealbumin is associated with visceral fat mass in patients receiving hemodialysis. J Ren Nutr 2013; 23:406-10. [PMID: 23623396 DOI: 10.1053/j.jrn.2013.02.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2012] [Revised: 01/27/2013] [Accepted: 02/12/2013] [Indexed: 01/15/2023] Open
Abstract
OBJECTIVE Albumin and prealbumin are associated with nutritional status and inflammatory status. Each has a residual effect on mortality outcomes when included in regression models that include the other. Prealbumin is increased in the obese mouse model as a consequence of stabilization of prealbumin by retinol binding protein 4 (RBP4) secreted by adipocytes. We carried out this study to establish the contribution of adiposity to prealbumin levels in prevalent patients receiving dialysis and the relationship of prealbumin to RBP4. DESIGN AND METHODS We determined whether prealbumin was associated with adiposity in patients receiving hemodialysis (HD), controlling for the effects of inflammation and nutrition. We evaluated body composition in 48 prevalent patients receiving HD by magnetic resonance imaging (MRI), measuring total skeletal muscle mass (SM), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and serum albumin, prealbumin, RBP4, and interleukin-6 (IL-6) levels. We used normalized protein catabolic rate (nPCR) to report nutrition and separately analyzed the determinants of albumin and then of prealbumin by multiple stepwise regression. RESULTS Thirty-two patients were women, 16 patients were diabetic, and median age and body mass index were 54.5 and 27.3 kg/m(2), respectively. Median total adipose tissue (TAT) was 24.3 kg and VAT was 3.25 kg. Prealbumin was positively associated with VAT, nPCR, and RBP4 and was negatively associated with IL-6; r(2) for the model was 0.64. By contrast, albumin was positively associated with nPCR and negatively associated with IL-6 but not with any measure of adiposity (r(2) for the model = 0.2). CONCLUSIONS Prealbumin, like albumin, is associated with markers of nutrition (nPCR) and inflammation, but unlike albumin, prealbumin levels are positively associated with visceral adiposity.
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Affiliation(s)
- Alessio Molfino
- Department of Internal Medicine, Division of Nephrology, University of California, Davis, Davis, California; Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
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21
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Wang MN, Han YB, Li Q, Guo L, Yang YM, Wang W, Zhang JC. Higher serum retinol binding protein 4 may be a predictor of weak metabolic control in chinese patients with type 2 diabetes mellitus. J Int Med Res 2013; 40:1317-24. [PMID: 22971483 DOI: 10.1177/147323001204000410] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE To investigate relationships between serum levels of retinol binding protein 4 (RBP4) and clinical and metabolic variables in Chinese patients with type 2 diabetes mellitus. METHODS A total of 513 patients (286 males/227 females) provided clinical and lifestyle data and blood and urine samples for analysis. Patients were stratified into four quartile groups according to serum RBP4 concentrations. RESULTS RBP4 concentration was independently associated with gender, systolic blood pressure, serum triglyceride and creatinine levels, and estimated glomerular filtration rate (eGFR). Hypertension, dyslipidaemia, micro albuminuria and impaired eGFR (<60 ml/min per 1.73 m2) were significantly more prevalent in patients with the highest RBP4 levels than in those with the lowest levels. Increased serum RBP4 was associated with increased risk of hypertension, dyslipidaemia, micro albuminuria and impaired eGFR after adjusting for gender, age, body mass index and duration of diabetes. CONCLUSION Serum RBP4 may be a useful marker of overall metabolic control in Chinese patients with type 2 diabetes mellitus.
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Affiliation(s)
- M N Wang
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Harbin Medical University and The Key Laboratory of Hormonal and Endocrine Diseases, Harbin Medical University, Harbin, Heilongjiang Province, China
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22
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Richter J, Focke D, Ebert T, Kovacs P, Bachmann A, Lössner U, Kralisch S, Kratzsch J, Beige J, Anders M, Bast I, Blüher M, Stumvoll M, Fasshauer M. Serum levels of the adipokine progranulin depend on renal function. Diabetes Care 2013; 36:410-4. [PMID: 23033238 PMCID: PMC3554312 DOI: 10.2337/dc12-0220] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Progranulin has recently been introduced as a novel adipokine inducing insulin resistance and obesity. In the current study, we investigated renal elimination, as well as association of the adipokine with markers of the metabolic syndrome. RESEARCH DESIGN AND METHODS Progranulin serum levels were quantified by enzyme-linked immunosorbent assay and correlated to anthropometric and biochemical parameters of renal function and glucose and lipid metabolism, as well as inflammation, in 532 patients with stages 1-5 of chronic kidney disease (CKD). RESULTS Median serum progranulin levels adjusted for age, sex, and BMI were significantly different between CKD stages with highest values detectable in stage 5 (stage 1, 58.3 µg/L; stage 2, 63.0 µg/L; stage 3, 65.4 µg/L; stage 4, 68.8 µg/L; and stage 5, 90.6 µg/L). Furthermore, CKD stage was the strongest independent predictor of circulating progranulin in our cohort. In addition, high-sensitivity interleukin-6 and adiponectin remained significantly and independently correlated with the adipokine. CONCLUSIONS We demonstrate that progranulin serum levels increase with deteriorating renal function. These findings are in accordance with the hypothesis that renal clearance is a major elimination route for circulating progranulin. Furthermore, the adipokine is positively and independently associated with markers of inflammation and adiponectin.
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Affiliation(s)
- Judit Richter
- Department of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany
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Choi KM, Hwang SY, Hong HC, Yang SJ, Choi HY, Yoo HJ, Lee KW, Nam MS, Park YS, Woo JT, Kim YS, Choi DS, Youn BS, Baik SH. C1q/TNF-related protein-3 (CTRP-3) and pigment epithelium-derived factor (PEDF) concentrations in patients with type 2 diabetes and metabolic syndrome. Diabetes 2012; 61:2932-6. [PMID: 22837306 PMCID: PMC3478553 DOI: 10.2337/db12-0217] [Citation(s) in RCA: 74] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Recent studies have suggested that a novel adipokine, C1q/tumor necrosis factor-related protein-3 (CTRP-3), a paralog of adiponectin, may play an important role in the regulation of glucose metabolism and innate immunity. Pigment epithelium-derived factor (PEDF), a multifunctional protein with antioxidant and anti-inflammatory properties, is associated with insulin resistance and metabolic syndrome. We examined circulating CTRP-3 and PEDF concentrations in 345 subjects with diverse glucose tolerance statuses. Furthermore, we evaluated the involvement of CTRP-3 and PEDF with cardiometabolic risk factors including insulin resistance, high-sensitivity C-reactive protein (hsCRP), estimated glomerular filtration rate (eGFR), and brachial-ankle pulse wave velocity (baPWV). CTRP-3 concentrations were significantly higher in patients with type 2 diabetes or prediabetes than the normal glucose tolerance group, whereas PEDF levels were not different. Subjects with metabolic syndrome showed significantly higher levels of both CTRP-3 and PEDF compared with subjects without metabolic syndrome. Both CTRP-3 and PEDF were significantly associated with cardiometabolic parameters, including waist-to-hip ratio, triglycerides, HDL-cholesterol, alanine aminotransferase, eGFR, hsCRP, and baPWV. In conclusion, circulating CTRP-3 concentrations were elevated in patients with glucose metabolism dysregulation. Both CTRP-3 and PEDF concentrations were increased in subjects with metabolic syndrome and associated with various cardiometabolic risk factors.
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Affiliation(s)
- Kyung Mook Choi
- Department of Internal Medicine, Division of Endocrinology and Metabolism, College of Medicine, Korea University, Seoul, Korea
| | - Soon Young Hwang
- Department of Biostatistics, College of Medicine, Korea University, Seoul, Korea
| | - Ho Cheol Hong
- Department of Internal Medicine, Division of Endocrinology and Metabolism, College of Medicine, Korea University, Seoul, Korea
| | - Sae Jeong Yang
- Department of Internal Medicine, Division of Endocrinology and Metabolism, College of Medicine, Korea University, Seoul, Korea
| | - Hae Yoon Choi
- Department of Internal Medicine, Division of Endocrinology and Metabolism, College of Medicine, Korea University, Seoul, Korea
| | - Hye Jin Yoo
- Department of Internal Medicine, Division of Endocrinology and Metabolism, College of Medicine, Korea University, Seoul, Korea
| | - Kwan Woo Lee
- Department of Internal Medicine, College of Medicine, Ajou University, Suwon, Korea
| | - Moon Suk Nam
- Department of Internal Medicine, College of Medicine, Inha University, Incheon, Korea
| | - Yong Soo Park
- Department of Internal Medicine, College of Medicine, Hanyang University, Seoul, Korea
| | - Jeong Taek Woo
- Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Young Seol Kim
- Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Dong Seop Choi
- Department of Internal Medicine, Division of Endocrinology and Metabolism, College of Medicine, Korea University, Seoul, Korea
| | | | - Sei Hyun Baik
- Department of Internal Medicine, Division of Endocrinology and Metabolism, College of Medicine, Korea University, Seoul, Korea
- Corresponding author: Sei Hyun Baik,
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Stepan H, Philipp A, Roth I, Kralisch S, Jank A, Schaarschmidt W, Lössner U, Kratzsch J, Blüher M, Stumvoll M, Fasshauer M. Serum levels of the adipokine zinc-α2-glycoprotein are increased in preeclampsia. J Endocrinol Invest 2012; 35:562-5. [PMID: 21791968 DOI: 10.3275/7877] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
BACKGROUND Preeclampsia (PE) is associated with facets of the metabolic syndrome and an increased future metabolic and cardiovascular risk for mother and newborn. Recently, zinc-α2-glycoprotein (ZAG) has been proposed as a new adipokine involved in the pathogenesis of obesity. AIM In the current study, we investigated ZAG serum levels in PE patients as compared to healthy gestational age-matched controls. SUBJECTS AND METHODS We quantified serum concentrations of ZAG in patients with PE (no.=37) as compared to healthy gestational age-matched controls (no.=37) by enzyme-linked immunosorbent assay. Furthermore, association of this adipokine with renal function, glucose and lipid metabolism, as well as inflammation was studied. RESULTS Median serum ZAG levels were 1.4-fold higher in PE patients (58.8 mg/l) as compared to controls (41.9 mg/l) (p<0.01). Furthermore, circulating ZAG was positively correlated to systolic and diastolic blood pressure, creatinine, triglycerides, and leptin in univariate analyses. In multiple regression analysis, creatinine remained independently associated with ZAG. CONCLUSIONS We demonstrate that maternal ZAG serum concentrations are significantly increased in PE. Furthermore, renal function is an independent predictor of circulating ZAG.
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Affiliation(s)
- H Stepan
- University of Leipzig, Department of Obstetrics, Leipzig, Germany
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25
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Thomsen KL, Sandahl TD, Holland-Fischer P, Jessen N, Frystyk J, Flyvbjerg A, Grønbæk H, Vilstrup H. Changes in adipokines after transjugular intrahepatic porto-systemic shunt indicate an anabolic shift in metabolism. Clin Nutr 2012; 31:940-5. [PMID: 22541535 DOI: 10.1016/j.clnu.2012.04.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2011] [Revised: 03/15/2012] [Accepted: 04/09/2012] [Indexed: 02/09/2023]
Abstract
BACKGROUND & AIMS Decompressing the portal hypertension by inserting a transjugular intrahepatic porto-systemic shunt (TIPS) in undernourished liver cirrhosis patients results in gains in body weight. It is important to understand whether this reflects an advantageous or unfavourable shift in nutrition status. This to some extent can be judged from the changes in the patients' adipokine patterns. We, therefore, examined the circulating levels of the most important adipokines before and after the TIPS procedure. METHODS Twenty-five liver cirrhosis patients were examined before TIPS insertion and followed for six months after the procedure. Their body composition was determined by the bioimpedance technique. The serum concentrations of adiponectin, retinol binding protein 4 (RBP4), and leptin were measured. RESULTS The TIPS procedure induced a 12% increase in body cell mass (P = 0.03) but did not change the body fat mass. At six months, serum adiponectin was increased by 60% (mean ± SD, 10.7 ± 6.1 vs. 16.9 ± 8.9 mg/L; P = 0.001), serum RBP4 was decreased by 45% (28.6 ± 20.0 vs. 16.3 ± 9.6 mg/L; P = 0.01), and the leptin levels remained unchanged. CONCLUSIONS The TIPS-related tissue build up was accompanied by increased adiponectin and decreased RBP4. Such changes are associated with an anabolic condition where the adipose tissue possesses residual capacity for energy storage. TIPS, therefore, can be considered to be nutritionally beneficial to cirrhosis patients.
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Affiliation(s)
- Karen Louise Thomsen
- Department of Medicine V (Hepatology & Gastroenterology), Aarhus University Hospital, 44 Noerrebrogade, DK-8000 Aarhus C, Denmark.
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26
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Iwamoto M, Miyoshi T, Doi M, Takeda K, Kajiya M, Nosaka K, Nakayama R, Hirohata S, Usui S, Kusachi S, Sakane K, Nakamura K, Ito H. Elevated serum adipocyte fatty acid-binding protein concentrations are independently associated with renal dysfunction in patients with stable angina pectoris. Cardiovasc Diabetol 2012; 11:26. [PMID: 22433902 PMCID: PMC3353231 DOI: 10.1186/1475-2840-11-26] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2011] [Accepted: 03/21/2012] [Indexed: 12/17/2022] Open
Abstract
Background Chronic kidney disease (CKD) is associated with cardiovascular events. Adipocyte fatty acid-binding protein (A-FABP) plays an important role in atherosclerosis. We investigated whether plasma A-FABP is involved in renal function in patients with stable angina pectoris. Methods A total of 221 patients with significant coronary artery stenosis were enrolled after coronary angiography. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. The severity of coronary stenosis was assessed using a modified Gensini score and coronary angiography. Serum A-FABP levels were determined by enzyme-linked immunosorbent assay. Results Serum A-FABP levels were significantly correlated with both eGFR (r = -0.41, p < 0.01) and the severity of coronary artery stenosis (r = 0.16, p = 0.02), and these relationships remained significant after adjusting for confounding factors. The prevalence of CKD and multi-vessel disease was significantly higher among patients with serum A-FABP levels above the median value of 20.3 ng/ml than among patients with serum A-FABP levels below the median value (57% vs. 27%, p < 0.01 and 64% vs. 48%, p = 0.02, respectively). Multivariate analysis revealed that the presence of three-vessel disease in comparison with single-vessel disease was independently associated with the higher A-FABP (per doubling) (odds ratio; 2.26, 95% confidential interval; 1.28-3.98, p < 0.01) and tended to be associated with the lower eGFR (p = 0.06). Conclusion Serum A-FABP may have a significant role in the interplay between renal dysfunction and coronary atherosclerosis.
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Affiliation(s)
- Mutsumi Iwamoto
- Department of Cardiology, Kagawa Prefectural Central Hospital, Kagawa, Japan
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Yang Q, Eskurza I, Kiernan UA, Phillips DA, Blüher M, Graham TE, Kahn BB. Quantitative measurement of full-length and C-terminal proteolyzed RBP4 in serum of normal and insulin-resistant humans using a novel mass spectrometry immunoassay. Endocrinology 2012; 153:1519-27. [PMID: 22253430 PMCID: PMC3281532 DOI: 10.1210/en.2011-1750] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Serum retinol-binding protein 4 (RBP4) levels are increased in insulin-resistant humans and correlate with severity of insulin resistance in metabolic syndrome. Quantitative Western blotting (qWestern) has been the most accurate method for serum RBP4 measurements, but qWestern is technically complex and labor intensive. The lack of a reliable, high-throughput method for RBP4 measurements has resulted in variability in findings in insulin-resistant humans. Many commonly used ELISAs have limited dynamic range. Neither the current ELISAs nor qWestern distinguish among full-length and carboxyl terminus proteolyzed forms of circulating RBP4 that are altered in different medical conditions. Here, we report the development of a novel quantitative mass spectrometry immunoaffinity assay (qMSIA) to measure full-length and proteolyzed forms of RBP4. qMSIA and qWestern of RBP4 were performed in identical serum aliquots from insulin-sensitive/normoglycemic or insulin-resistant humans with impaired glucose tolerance or type 2 diabetes. Total RBP4 qMSIA measurements were highly similar to qWestern and correlated equally well with clinical severity of insulin resistance (assessed by clamp glucose disposal rate, r = -0.74), hemoglobin A1c (r = 0.63), triglyceride/high-density lipoprotein (r = 0.55), waist/hip (r = 0.61), and systolic blood pressure (r = 0.53, all P < 0.001). Proteolyzed forms of RBP4 accounted for up to 50% of total RBP4 in insulin-resistant subjects, and des(Leu)-RBP4 (cleavage of last leucine) correlated highly with insulin resistance (assessed by glucose disposal rate, r = -0.69). In multiple regression analysis, insulin resistance but not glomerular filtration rate was the strongest, independent predictor of serum RBP4 levels. Thus, qMSIA provides a novel tool for accurately measuring serum RBP4 levels as a biomarker for severity of insulin resistance and risk for type 2 diabetes and metabolic syndrome.
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Affiliation(s)
- Qin Yang
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, CLS 747, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
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Chen CH, Hsieh TJ, Lin KD, Lin HY, Lee MY, Hung WW, Hsiao PJ, Shin SJ. Increased unbound retinol-binding protein 4 concentration induces apoptosis through receptor-mediated signaling. J Biol Chem 2012; 287:9694-9707. [PMID: 22308028 DOI: 10.1074/jbc.m111.301721] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
The increase of apo-/holo-retinol-binding protein 4 (RBP4) concentrations has been found in subjects with renal dysfunction and even in diabetic patients with microalbuminuria. Holo-RBP4 is recognized to possess cytoprotective function. Therefore, we supposed that the relative increase in apo-RBP4 might induce cell damage. In this study, we investigated the signal transduction that activated apoptosis in response to the increase of apo-/holo-RBP4 concentration. We found that increase of apo-/holo-RBP4 concentration ratio delayed the displacement of RBP4 with "stimulated by retinoic acid 6" (STRA6), enhanced Janus kinase 2 (JAK2)/STAT5 cascade, up-regulated adenylate cyclase 6 (AC6), increased cAMP, enhanced JNK1/p38 cascade, suppressed CRBP-I/RARα (cellular retinol-binding protein/retinoic acid receptor α) expression, and led to apoptosis in HK-2 and human umbilical vein endothelial cells. Furthermore, STRA6, JAK2, STAT5, JNK1, or p38 siRNA and cAMP-PKA inhibitor reversed the repression of CRBP-I/RARα and apoptosis in apo-RBP4 stimulation. In conclusion, this study indicates that the increase of apo-/holo-RBP4 concentration may influence STRA6 signaling, finally causing apoptosis.
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Affiliation(s)
- Chao-Hung Chen
- Graduate Institute of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Tusty-Jiuan Hsieh
- School of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Kun-Der Lin
- Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Hsing-Yi Lin
- Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Mei-Yueh Lee
- Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Wei-Wen Hung
- Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Pi-Jung Hsiao
- School of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Shyi-Jang Shin
- School of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
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Decrease of serum chemerin concentration in patients with end stage renal disease after successful kidney transplantation. ACTA ACUST UNITED AC 2012; 173:55-9. [DOI: 10.1016/j.regpep.2011.09.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2011] [Revised: 08/26/2011] [Accepted: 09/16/2011] [Indexed: 12/20/2022]
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Serum fatty acid-binding protein 4 is a predictor of cardiovascular events in end-stage renal disease. PLoS One 2011; 6:e27356. [PMID: 22102888 PMCID: PMC3213139 DOI: 10.1371/journal.pone.0027356] [Citation(s) in RCA: 80] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2011] [Accepted: 10/14/2011] [Indexed: 11/19/2022] Open
Abstract
Background Fatty acid-binding protein 4 (FABP4/A-FABP/aP2), a lipid chaperone, is expressed in both adipocytes and macrophages. Recent studies have shown that FABP4 is secreted from adipocytes and that FABP4 level is associated with obesity, insulin resistance, and atherosclerosis. However, little is known about the impact of FABP4 concentrations on prognosis. We tested the hypothesis that FABP4 level predicts prognosis of patients with end-stage renal disease (ESRD), a group at high risk for atherosclerosis-associated morbidity and mortality. Methods and Results Biochemical markers including FABP4 were determined in 61 ESRD patients on chronic hemodialysis (HD). Serum FABP4 level in females (404.2±30.5 ng/ml) was significantly higher than that in males (315.8±30.0 ng/ml), and the levels in ESRD patients were about 20-times higher than those in age-, gender- and body mass index (BMI)-matched control subjects with normal renal function. FABP4 level was decreased by 57.2% after HD and was positively correlated with blood pressure, BMI, and levels of lipids and insulin. Multiple regression analysis indicated that HD duration, BMI, and triglycerides level were independent determinants for FABP4 level. ESRD patients with high FABP4 levels had higher cardiovascular mortality during the 7-year follow-up period. Cox proportional hazard regression analysis showed that logarithmically transformed FABP4 level was an independent predictor of cardiovascular death adjusted for age, gender, HD duration, BMI, and triglycerides level (hazard ratio, 7.75; 95% CI, 1.05–25.31). Conclusion These findings suggest that FABP4 level, being related to adiposity and metabolic disorders, is a novel predictor of cardiovascular mortality in ESRD.
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Abstract
Adipose tissue is an endocrine organ secreting biologically active factors called adipokines that act on both local and distant tissues. Adipokines have an important role in the development of obesity-related comorbidities not only in adults but also in children and adolescents. Retinol binding protein 4 (RBP4) is a recently identified adipokine suggested to link obesity with its comorbidities, especially insulin resistance, type 2 diabetes (T2D), and certain components of the metabolic syndrome. However, data, especially resulting from the clinical studies, are conflicting. In this review, we summarize up-to-date knowledge on RBP4's role in obesity, development of insulin resistance, and T2D. Special attention is given to studies on children and adolescents. We also discuss the role of possible confounding factors that should be taken into account when critically evaluating published studies or planning new studies on this exciting adipokine.
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Affiliation(s)
- Primoz Kotnik
- Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany
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Ng DPK, Salim A, Lim XL, Nurbaya S. Estimated glomerular filtration rate and its association with the retinol-binding protein 4 (RBP4) locus on human chromosome 10q23. Nephrol Dial Transplant 2011; 27:1511-5. [PMID: 21821833 DOI: 10.1093/ndt/gfr442] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND We tested for associations between estimated glomerular filtration rate (eGFR) and retinol-binding protein 4 (RBP4) haplotypes found on human chromosome 10q23. This locus had been linked to eGFR in a previous linkage scan in patients with Type 2 diabetes mellitus. METHODS We analysed 469 patients with Type 2 diabetes and 174 normoalbuminuric controls for associations between RBP4 haplotypes and eGFR. For comparison with controls, 295 cases with proteinuria/end-stage renal disease were tested for associations with advanced diabetic nephropathy. Genotyping was performed using high-resolution DNA melting assays. Data analysis was performed using the haplo.stats package. RESULTS Genetic variations in RBP4 were not associated with advanced diabetic nephropathy. Compared with the common A/G/G/C haplotype, C/A/A/C carriers among the normoalbuminuric controls had higher eGFR values among younger patients but lower eGFRs among the older patients (effect size=2.2, P=3.3×10(-7)). Furthermore, while eGFR values were fairly consistent over the range of systolic blood pressure (SBP) values for the common haplotype, eGFR in C/A/A/C carriers increased with SBP (effect size=3.6, P=1.5×10(-2)). There was a significant interaction between the C/A/A/C haplotype and HbA1c as they affect eGFR compared to the common haplotype (effect size=2.1, P=2.1×10(-3)). Power calculations demonstrated that our study had >90% power to detect the observed interactions even while performing multiple hypotheses testing. The interaction between SBP and the C/A/A/C haplotype remained significant (P=2.8×10(-2)) even when these three haplotype-environment interactions were simultaneously estimated. CONCLUSION RBP4 haplotypes may be important in genetically modulating renal function in response to environmental challenges among patients with Type 2 diabetes.
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Affiliation(s)
- Daniel P K Ng
- Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
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Barazzoni R, Zanetti M, Semolic A, Pirulli A, Cattin MR, Biolo G, Bosutti A, Panzetta G, Bernardi A, Guarnieri G. High plasma retinol binding protein 4 (RBP4) is associated with systemic inflammation independently of low RBP4 adipose expression and is normalized by transplantation in nonobese, nondiabetic patients with chronic kidney disease. Clin Endocrinol (Oxf) 2011; 75:56-63. [PMID: 21521262 DOI: 10.1111/j.1365-2265.2011.03990.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVE Adipose-secreted retinol binding protein 4 (RBP4) circulates in free (active) and transthyretin (TTR)-bound forms and may be associated with obesity-related inflammation. Potential involvement of plasma and adipose RBP4 in systemic inflammation in the absence of obesity and diabetes is unknown. Inflammation reduces survival in chronic kidney disease (CKD) [particularly in maintenance haemodialysis (MHD)], and plasma RBP4 may increase with renal dysfunction. We investigated (i) potential associations between RBP4 and inflammation in CKD and (ii) the role of adipose tissue in this putative interaction. DESIGN Cross-sectional. PATIENTS Nonobese, nondiabetic patients with CKD undergoing conservative (CT: n = 10) or MHD treatment (n = 25) and healthy control subjects (C: n = 11). Renal transplant recipients (n = 5) were studied to further assess the impact of restored near-normal renal function. MEASUREMENTS Plasma RBP4, TTR and C-reactive protein (CRP), adipose RBP4 expression. RESULTS Plasma RBP4, TTR and CRP were highest in MHD (P < 0·05). Adipose RBP4 mRNA was, however, comparably low in CT and MHD (P < 0·05 vs C), and all parameters were normalized in transplant recipients (P < 0·05 vs MHD). In all subjects (n = 51), creatinine and TTR (P < 0·05) but not adipose RBP4 mRNA were associated with plasma RBP4. Plasma RBP4 but not its adipose expression was in turn associated positively (P < 0·05) with CRP independently of creatinine-TTR. CONCLUSIONS High plasma RBP4 and inflammation are clustered in CKD in the absence of obesity and diabetes and are normalized by transplantation. Adipose RBP4 expression is not involved in plasma RBP4 elevation, which appears to be mainly because of passive accumulation, or in CKD-associated inflammation.
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Affiliation(s)
- Rocco Barazzoni
- Clinica Medica, Department of Medical, Technological and Translational Sciences, University of TriesteDivision of Nephrology, Azienda Ospedaliero-Universitaria Ospedali Riuniti, TriesteDivision of Nephrology, Ospedale S. Maria della Misericordia, Rovigo, Italy
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Christou GA, Tellis CC, Elisaf MS, Tselepis AD, Kiortsis DN. The changes in plasma retinol-binding protein 4 levels are associated with those of the apolipoprotein B-containing lipoproteins during dietary and drug treatment. Angiology 2011; 63:67-75. [PMID: 21602259 DOI: 10.1177/0003319711407628] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
We investigated the association between retinol-binding protein 4 (RBP(4)) and apolipoprotein B (ApoB)-containing lipoproteins. Obese or overweight, hypertriglyceridemic patients underwent the following interventions for 3 months: (1) Diet (n = 20), (2) Diet + fenofibrate (n = 18), (3) Diet + rimonabant (n = 8). Circulating RBP4 decreased during dietary treatment. The percentage change in RBP(4) was positively correlated with the percentage changes in very-low density lipoprotein cholesterol (r = .570, P = .02), low-density lipoprotein cholesterol ([LDL-C]; r = .605, P = .01), ApoB (r = .705, P = .007), and small dense LDL-C ([sdLDL-C]; r = .872, P < .001). The percentage change in RBP4 was the best predictor of the percentage changes in sdLDL-C and ApoB. Rimonabant treatment reduced RBP4, whereas fenofibrate increased RBP4 during the first month of therapy followed by a subsequent decrease. In conclusion, RBP4 may significantly influence the metabolic pathways responsible for changes in ApoB lipoprotein subspecies, thus RBP4 may be associated with cardiovascular disease risk.
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Affiliation(s)
- Georgios A Christou
- Laboratory of Physiology, Medical School, University of Ioannina, Ioannina, Greece
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35
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Toruner F, Altinova AE, Akturk M, Kaya M, Arslan E, Bukan N, Kan E, Yetkin I, Arslan M. The relationship between adipocyte fatty acid binding protein-4, retinol binding protein-4 levels and early diabetic nephropathy in patients with type 2 diabetes. Diabetes Res Clin Pract 2011; 91:203-7. [PMID: 21176857 DOI: 10.1016/j.diabres.2010.11.011] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2010] [Revised: 10/29/2010] [Accepted: 11/08/2010] [Indexed: 01/06/2023]
Abstract
Adipocyte fatty acid binding protein-4 (A-FABP4) and retinol binding protein-4 (RBP4) have recently been linked to type 2 diabetes mellitus (DM). Serum A-FABP4 and RBP4 levels and their relationships with early diabetic nephropathy were examined in 87 type 2 diabetic patients. The patients with diabetic nephropathy showed high A-FABP4 levels compared to the patients without diabetic nephropathy (p=0.0001). Log A-FABP4 correlated positively with age (p=0.02), log duration of diabetes (p=0.04), log body mass index (BMI) (p=0.0001), log creatinine (p=0.007), log C-reactive protein (CRP) (p=0.01), log albumin excretion rate (AER) (p=0.001), and negatively with MDRD-GFR (p=0.0001). Serum RBP4 levels were similar between the patients with and without diabetic nephropathy. RBP4 correlated positively with triglycerides (p=0.001), log creatinine (p=0.009), and negatively with MDRD-GFR (p=0.04). In regression analysis, log A-FABP4 was associated with age, sex, log BMI, and log AER (r(2)=0.43) and RBP4 was associated with triglycerides and log creatinine (r(2)=0.22). In conclusion, we found high serum A-FABP4 but unchanged RBP4 concentrations and their associations with renal function and early diabetic nephropathy in type 2 DM.
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Affiliation(s)
- Fusun Toruner
- Department of Endocrinology and Metabolism, Gazi University Faculty of Medicine, Besevler, 06500 Ankara, Turkey.
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Vitamin A metabolism and adipose tissue biology. Nutrients 2011; 3:27-39. [PMID: 22254074 PMCID: PMC3257733 DOI: 10.3390/nu3010027] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2010] [Revised: 12/14/2010] [Accepted: 01/05/2011] [Indexed: 01/01/2023] Open
Abstract
In recent years, the importance of vitamin A in adipose tissue biology, obesity and type II diabetes has become apparent. This review focuses on recent developments within the area of vitamin A and adipose tissue biology. Adipose tissue has an active vitamin A metabolism as it not only stores vitamin A but retinol is also converted to its active metabolite retinoic acid. Several mouse models point to a relationship between vitamin A metabolism and the development of adiposity. Similarly, in vitro studies provide new molecular mechanisms for the function of different forms of vitamin A and retinol- or retinoic acid-binding proteins in adipose tissue.
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Chu CH, Lam HC, Lee JK, Lu CC, Sun CC, Cheng HJ, Wang MC, Chuang MJ. Elevated serum retinol-binding protein 4 concentrations are associated with chronic kidney disease but not with the higher carotid intima-media thickness in type 2 diabetic subjects. Endocr J 2011; 58:841-7. [PMID: 21817822 DOI: 10.1507/endocrj.ej11-0028] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
To examine the association of serum retinol-binding protein 4 (RBP4) concentrations with carotid intima-media thickness (CIMT) in type 2 diabetic subjects with chronic kidney disease (CKD). A total of 239 type 2 diabetic patients (64 ± 13 years, 154 males) were divided into two groups: one with CKD, defined as estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73m(2) (n = 86), and one without (n = 153). We recorded clinical and biochemical data as well as CIMT. The patients with CKD were older, had had diabetes mellitus longer, and had higher incidence of hypertension, dyslipidemia and microalbuminuria than those without. They also had higher serum concentrations of RBP4 (44.8 ± 6.4 vs 39.5 ± 4.9 µg/mL, p < 0.001), higher mean CIMT (0.75 ± 0.16 vs 0.69 ± 0.14 mm, p = 0.0070), and higher incidence of carotid plaques (27.9 vs 11.8 %, p = 0.002). The RBP4 were negatively correlated with eGFR (r = -0.514, p < 0.001). However, the RBP4 were not correlated with mean CIMT (r = 0.065, p = 0.318). Moreover, when dividing the patients into two groups by the mean CIMT, those with mean CIMT above 0.71 mm did not have different RBP4 concentrations compared with those below (41.5 ± 5.7 vs 41.3 ± 6.3 µg/mL, p = 0.856). In conclusion, we observed an elevation of serum RBP4 concentrations and CIMT levels in type 2 diabetic subjects with CKD. However, the elevated RBP4 were not associated with the higher CIMT among these patients.
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Affiliation(s)
- Chih-Hsun Chu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
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Akbay E, Muslu N, Nayir E, Ozhan O, Kiykim A. Serum retinol binding protein 4 level is related with renal functions in Type 2 diabetes. J Endocrinol Invest 2010; 33:725-9. [PMID: 20436266 DOI: 10.1007/bf03346678] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
AIM We aimed to evaluate the metabolic parameters and diabetes complications which would probably affect the serum retinol-binding protein 4 (RBP4) levels in Type 2 diabetic individuals. In addition to serum RBP4 concentration, the levels of its ligands, serum retinol and transthyretin (TTR) were also considered in this evaluation. SUBJECTS AND METHODS Serum RBP4, retinol, and TTR levels were measured in 53 Type 2 diabetic subjects and 30 body mass index (BMI)- matched controls. The molar ratios of RBP4 to retinol and RBP4 to TTR were compared. RESULTS While the RBP4 values were similar to those in the control group in Type 2 diabetic patients, the molar ratio of RBP4 to TTR was found to be higher than that of the control group. The serum RBP4 levels in patients who had retinopathy and macrovascular disease were similar to those in patients who did not. However, the RBP4 levels, molar ratios of RBP4 to retinol and RBP4 to TTR in micro- macroalbuminuric patients were found to be significantly higher than in normoalbuminuric subjects and controls. There was no correlation between the RBP4 levels and the patients' age, BMI, duration of diabetes, LDL, triglyceride, serum creatinine, and glycated hemoglobin values. Micro-macroalbuminuria and estimated glomerular filtration rate were independent determinants for increased serum RBP4 levels. CONCLUSION According to the data obtained from this study, diabetic retinopathy and cardiovascular complications do not affect the serum RBP4 level in Type 2 diabetes. Renal functions rather than the metabolic factors of diabetes determine the RBP4 level and its relation with its ligands.
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Affiliation(s)
- E Akbay
- Department of Endocrinology and Metabolism, Mersin University Medical Faculty, Mersin, Turkey.
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Kalousová M, Kuběna AA, Koštířová M, Vinglerová M, Ing OM, Dusilová-Sulková S, Tesař V, Zima T. Lower Retinol Levels as an Independent Predictor of Mortality in Long-term Hemodialysis Patients: A Prospective Observational Cohort Study. Am J Kidney Dis 2010; 56:513-21. [DOI: 10.1053/j.ajkd.2010.03.031] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2009] [Accepted: 03/25/2010] [Indexed: 12/13/2022]
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Sommer G, Kralisch S, Kloting N, Kamprad M, Schrock K, Kratzsch J, Tonjes A, Lossner U, Bluher M, Stumvoll M, Fasshauer M. Visfatin is a positive regulator of MCP-1 in human adipocytes in vitro and in mice in vivo. Obesity (Silver Spring) 2010; 18:1486-92. [PMID: 20035281 DOI: 10.1038/oby.2009.462] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Visfatin is a proinflammatory and potentially insulin-mimetic adipokine contributing to whole body glucose and lipid metabolism, as well as atherosclerosis. Monocyte chemoattractant protein (MCP)-1 is an adipocyte-secreted protein which might play a crucial role in metabolic and vascular disease. MCP-1 expression and secretion after visfatin treatment were determined by quantitative real-time reverse transcription-PCR and enzyme-linked immunosorbent assay (ELISA) in fully differentiated human mesenchymal stem cell-derived adipocytes (hMSC-Ads) in vitro. In addition, circulating levels of MCP-1 and visfatin were quantified by ELISA in 60 patients (30 nondiabetic, 30 diabetic) and MCP-1 serum levels in mice were determined after visfatin treatment in vivo. Interestingly, protein secretion and mRNA production of MCP-1 were induced significantly in hMSC-Ads after visfatin stimulation. Visfatin-induced MCP-1 secretion 1.9-fold after 8 h and 2.5-fold after 24 h relative to untreated cells (P < 0.05). MCP-1 mRNA synthesis was significantly stimulated by visfatin with maximal upregulation detectable at 250 ng/ml visfatin and after 4 h of treatment. Signaling studies suggested that p44/42 mitogen-activated protein (MAP) kinase is involved in visfatin-induced MCP-1 mRNA expression in hMSC-Ads. Detectability of visfatin in serum predicted circulating MCP-1 independent of age and gender in humans in vivo. MCP-1 serum levels were significantly increased more than twofold after visfatin treatment in mice in vivo. Taken together, our results demonstrate that visfatin upregulates MCP-1 supporting a possible role of MCP-1 in mediating the proinflammatory effects of visfatin.
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Affiliation(s)
- Grit Sommer
- Department of Internal Medicine III, University of Leipzig, Leipzig, Germany
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41
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Wang SN, Yeh YT, Wang ST, Chen YL, Chuang SC, Ker CG, Lee KT. Decreased retinol binding protein 4 concentrations are associated with cholesterol gallstone disease. J Formos Med Assoc 2010; 109:422-429. [PMID: 20610143 DOI: 10.1016/s0929-6646(10)60073-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2009] [Revised: 07/06/2009] [Accepted: 09/17/2009] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND/PURPOSE Circulating retinol binding protein 4 (RBP4) is associated with a variety of obesity-related diseases. This study investigated whether there were aberrant concentrations of RBP4 in cholesterol gallstone disease. METHODS Serum RBP4 levels of 100 cholesterol gallstone patients and 147 healthy controls were measured by enzyme-linked immunosorbent assay and further correlated with clinical and biochemical characteristics, including insulin resistance and renal function. Gallstone specimens were obtained during laparoscopic cholecystectomy and analyzed for their chemical composition using Fourier transform infrared spectroscopy RESULTS Significantly lower serum RBP4 levels were found in patients with cholesterol gallstones in comparison with controls (30.57 +/- 13.64 mg/L vs. 41.52 +/- 20.25 mg/L, p<0.001). Lower serum RBP4 levels were also associated with gallstone occurrence (odds ratio = 0.93; 95% confidence interval = 0.88-0.96; p = 0.004). Serum RBP4 levels of all subjects were positively correlated with total cholesterol, triglyceride, creatinine, insulin resistance and albumin, and inversely correlated with aspartate aminotransferase and alanine aminotransferase. In multivariate analysis, cholesterol gallstone formation was significantly associated with a lower serum RBP4 level (odds ratio = 4.2; 95% confidence interval= 1.40-12.57; p = 0.010). RBP4 levels were significantly decreased regardless of renal function in patients with gallstones, but levels increased proportionate to renal dysfunction in people without gallstones. CONCLUSION Circulating RBP4 decreases in cholesterol gallstone disease independent of renal function. Further studies are needed to investigate the relationship between liver function and RBP4 levels in these patients.
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Affiliation(s)
- Shen-Nien Wang
- Department of Surgery, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan
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Peritoneal adipocytes and their role in inflammation during peritoneal dialysis. Mediators Inflamm 2010; 2010:495416. [PMID: 20454534 PMCID: PMC2864891 DOI: 10.1155/2010/495416] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2009] [Revised: 01/27/2010] [Accepted: 02/17/2010] [Indexed: 01/04/2023] Open
Abstract
Adipose tissue is a major site of chronic inflammation associated with peritoneal dialysis (PD) frequently complicating peritonitis. Adiposity-associated inflammation plays a significant contributory role in the development of chronic inflammation in patients undergoing maintenance PD. However, the molecular and cellular mechanisms of this link remain uncertain. Adipose tissue synthesizes different adipokines and cytokines that orchestrate and regulate inflammation, insulin action, and glucose metabolism locally and systemically. In return, inflammation retards adipocyte differentiation and further exacerbates adipose dysfunction and inflammation. An understanding of the inflammatory roles played by adipose tissue during PD and the healing mechanism of injured mesothelium will help to devise new therapeutic approach to slow the progression of peritoneal damage during peritoneal dialysis. This article reviews the roles of peritoneal adipose tissue in chronic peritoneal inflammation under PD and in serosal repair during PD.
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Chiang SS, Tai CW, Chung CJ, Shiue HS, Chen JB, Su CT, Hsueh YM. Micronutrients and lifestyles in Taiwanese patients with stage 3 to 5 chronic kidney disease. Nutrition 2010; 26:276-82. [DOI: 10.1016/j.nut.2009.04.021] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2008] [Revised: 04/25/2009] [Accepted: 04/25/2009] [Indexed: 11/28/2022]
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Henze A, Frey SK, Raila J, Scholze A, Spranger J, Weickert MO, Tepel M, Zidek W, Schweigert FJ. Alterations of retinol-binding protein 4 species in patients with different stages of chronic kidney disease and their relation to lipid parameters. Biochem Biophys Res Commun 2010; 393:79-83. [DOI: 10.1016/j.bbrc.2010.01.082] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2010] [Accepted: 01/20/2010] [Indexed: 12/13/2022]
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Pfau D, Bachmann A, Lössner U, Kratzsch J, Blüher M, Stumvoll M, Fasshauer M. Serum levels of the adipokine chemerin in relation to renal function. Diabetes Care 2010; 33:171-3. [PMID: 19837789 PMCID: PMC2797967 DOI: 10.2337/dc09-1351] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To investigate serum levels of the adipokine chemerin in patients on chronic hemodialysis (CD) as compared with control patients with a glomerular filtration rate (GFR) >50 ml/min. RESEARCH DESIGN AND METHODS Chemerin was quantified by ELISA in control patients (n = 60) and CD patients (n = 60) and correlated with clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation, in both groups. RESULTS Median serum chemerin levels were more than twofold higher in CD patients (542.2 microg/l) compared with subjects with a GFR >50 ml/min (254.3 microg/l) (P < 0.001). Furthermore, GFR, as assessed by the original Modification of Diet in Renal Disease formula, independently predicted circulating chemerin concentrations in multiple regression analyses in both control patients (P < 0.05) and CD patients (P < 0.01). CONCLUSIONS We demonstrate that markers of renal function are independently related to circulating chemerin levels.
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Affiliation(s)
- Dörte Pfau
- Department of Internal Medicine III, University of Leipzig, Leipzig, Germany
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Chen CC, Wu JY, Chang CT, Tsai FJ, Wang TY, Liu YM, Tsui HC, Chen RH, Chiou SC. Levels of retinol-binding protein 4 and uric acid in patients with type 2 diabetes mellitus. Metabolism 2009; 58:1812-6. [PMID: 19709697 DOI: 10.1016/j.metabol.2009.06.013] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2009] [Revised: 06/12/2009] [Accepted: 06/26/2009] [Indexed: 10/20/2022]
Abstract
Retinol-binding protein 4 (RBP4) is a novel adipocytokine. It was observed that retinoid intoxication was related to acute attacks of gout. Furthermore, animal study has shown that colchicine inhibits RBP secretion. The aim of this study was to explore the association between RBP4 level and metabolic parameters especially uric acid in patients with type 2 diabetes mellitus. Serum RBP4 level was measured by a commercial competitive enzyme-linked immunosorbent assay kit, and its correlation with clinical and metabolic parameters was analyzed. Data on 885 subjects were used in the analysis. Pearson correlations revealed that serum RBP4 level correlated positively with age, waist circumference, waist-to-hip ratio, systolic blood pressure, total cholesterol, triglyceride, uric acid, creatinine, and urine albumin-to-creatinine ratio. Serum RBP4 level correlated negatively with estimated glomerular filtration rate but did not correlate with body mass index, homeostasis model assessment, A(1C), or high-sensitivity C-reactive protein. Multiple linear regression analysis with serum RBP4 level as the dependent variable revealed that total cholesterol, triglyceride, uric acid, and albumin-to-creatinine ratio correlated independently and positively with serum RBP4 level and that estimated glomerular filtration rate correlated independently and negatively with serum RBP4 level. In conclusion, RBP4 level was independently associated with uric acid level.
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Affiliation(s)
- Ching-Chu Chen
- Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung 40447, Taiwan.
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D'Apolito M, Du X, Zong H, Catucci A, Maiuri L, Trivisano T, Pettoello-Mantovani M, Campanozzi A, Raia V, Pessin JE, Brownlee M, Giardino I. Urea-induced ROS generation causes insulin resistance in mice with chronic renal failure. J Clin Invest 2009; 120:203-13. [PMID: 19955654 DOI: 10.1172/jci37672] [Citation(s) in RCA: 171] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2009] [Accepted: 10/07/2009] [Indexed: 12/30/2022] Open
Abstract
Although supraphysiological concentrations of urea are known to increase oxidative stress in cultured cells, it is generally thought that the elevated levels of urea in chronic renal failure patients have negligible toxicity. We previously demonstrated that ROS increase intracellular protein modification by O-linked beta-N-acetylglucosamine (O-GlcNAc), and others showed that increased modification of insulin signaling molecules by O-GlcNAc reduces insulin signal transduction. Because both oxidative stress and insulin resistance have been observed in patients with end-stage renal disease, we sought to determine the role of urea in these phenotypes. Treatment of 3T3-L1 adipocytes with urea at disease-relevant concentrations induced ROS production, caused insulin resistance, increased expression of adipokines retinol binding protein 4 (RBP4) and resistin, and increased O-GlcNAc-modified insulin signaling molecules. Investigation of a mouse model of surgically induced renal failure (uremic mice) revealed increased ROS production, modification of insulin signaling molecules by O-GlcNAc, and increased expression of RBP4 and resistin in visceral adipose tissue. Uremic mice also displayed insulin resistance and glucose intolerance, and treatment with an antioxidant SOD/catalase mimetic normalized these defects. The SOD/catalase mimetic treatment also prevented the development of insulin resistance in normal mice after urea infusion. These data suggest that therapeutic targeting of urea-induced ROS may help reduce the high morbidity and mortality caused by end-stage renal disease.
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Affiliation(s)
- Maria D'Apolito
- Institute of Pediatrics, University of Foggia, Viale Pinto 1 O.O.R.R., Foggia, Italy
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Frey SK, Spranger J, Henze A, Pfeiffer AFH, Schweigert FJ, Raila J. Factors that influence retinol-binding protein 4-transthyretin interaction are not altered in overweight subjects and overweight subjects with type 2 diabetes mellitus. Metabolism 2009; 58:1386-92. [PMID: 19501859 DOI: 10.1016/j.metabol.2009.05.003] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2009] [Revised: 04/08/2009] [Accepted: 05/01/2009] [Indexed: 10/20/2022]
Abstract
Retinol-binding protein 4 (RBP4) is an adipokine bound in plasma to transthyretin (TTR), which prevents its glomerular filtration and subsequent catabolism in the kidney. Alterations of this interaction have been suggested to be implicated in the elevation of RBP4 that are thought to contribute to the development of insulin resistance associated with obesity and type 2 diabetes mellitus (T2DM). However, the factors linking RBP4 to TTR in humans are not clear. Therefore, this study evaluated parameters influencing the RBP4-TTR interaction and their relation to obesity and T2DM. The RBP4 and TTR levels were quantified in plasma of 16 lean controls, 28 overweight controls, and 14 overweight T2DM patients by enzyme-linked immunosorbent assay. Transthyretin isoforms involved in RBP4 binding were determined by linear matrix-assisted laser desorption/ionization-time of flight-mass spectrometry after RBP4 coimmunoprecipitation. Holo-RBP4 (retinol-bound) and apo-RBP4 (retinol-free) were assessed by immunoblotting using nondenaturating polyacrylamide gel electrophoresis. Plasma levels of both RBP4 and TTR did not differ among the groups of lean controls, overweight controls, and overweight T2DM subjects. Using RBP4 immunoprecipitation, 4 mass signals were observed for TTR representing native, S-cysteinylated, S-cysteinglycinylated, and S-glutathionylated TTR. No differences in peak intensity of TTR isoforms were observed among the groups. Moreover, no differences in the ratio of holo- and apo-RBP4 were evident. The results suggest that circulating RBP4 and TTR were not affected by human obesity or T2DM, which might be attributed to the absence of alterations of TTR isoforms and the ratio of holo- and apo-RBP4 that might modify the TTR-RBP4 interaction.
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Affiliation(s)
- Simone K Frey
- Institute of Nutritional Science, University of Potsdam, D-14558 Nuthetal (Potsdam-Rehbrücke), Germany
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Ebert T, Bachmann A, Lössner U, Kratzsch J, Blüher M, Stumvoll M, Fasshauer M. Serum levels of angiopoietin-related growth factor in diabetes mellitus and chronic hemodialysis. Metabolism 2009; 58:547-51. [PMID: 19303977 DOI: 10.1016/j.metabol.2008.11.016] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2008] [Accepted: 11/18/2008] [Indexed: 11/27/2022]
Abstract
Angiopoietin-related growth factor (AGF) was recently introduced as a novel liver-derived protein that antagonizes obesity and insulin resistance. In the current study, we investigated circulating AGF levels in relation to renal function and type 2 diabetes mellitus (T2DM). Angiopoietin-related growth factor was determined by enzyme-linked immunosorbent assay in subjects with a glomerular filtration rate greater than 50 mL/min (n = 60, 30 diabetic and 30 nondiabetic) and in patients on chronic hemodialysis (CD; n = 60, 32 diabetic and 28 nondiabetic). Furthermore, AGF was correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, as well as inflammation. Median serum AGF levels were significantly lower in CD patients (125.9 +/- 96.3 microg/L) as compared with subjects with a glomerular filtration rate greater than 50 mL/min (164.0 +/- 95.4 microg/L) (P < .05). Furthermore, AGF serum levels were significantly increased in diabetic patients (161.7 +/- 114.2 microg/L) as compared with nondiabetic subjects (123.0 +/- 88.2 microg/L) (P < .01). Moreover, CD negatively and T2DM positively predicted AGF concentrations in multiple regression analysis. In addition, fasting serum glucose was independently and positively correlated with circulating AGF in all patients and controls. Our results suggest that renal dysfunction is negatively and T2DM is positively associated with AGF serum levels. Further studies are needed to better elucidate the physiologic significance of circulating AGF in human disease.
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Affiliation(s)
- Thomas Ebert
- Department of Internal Medicine III, University of Leipzig, 04103 Leipzig, Germany
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Effect of renal replacement therapy on retinol-binding protein 4 isoforms. Clin Chim Acta 2009; 401:46-50. [DOI: 10.1016/j.cca.2008.11.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2008] [Revised: 11/06/2008] [Accepted: 11/06/2008] [Indexed: 11/30/2022]
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