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Sano A, Sasaki M, Inoue J, Kakazu E, Ninomiya M, Tsuruoka M, Sato K, Onuki M, Sawahashi S, Ouchi K, Doi K, Katori Y, Masamune A. Type 2 Diabetes Mellitus Is a Risk Factor for Skeletal Muscle Loss in the Course of Dietary Treatment for Patients with Metabolic Dysfunction-associated Steatotic Liver Disease. Intern Med 2025; 64:631-641. [PMID: 39048367 DOI: 10.2169/internalmedicine.3787-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/27/2024] Open
Abstract
Objective This study assessed the impact of dietary therapy and reduced body weight on the loss of skeletal muscle in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods This was a single-center retrospective observational study. We enrolled 129 patients with MASLD who had undergone dietary therapy at our facility. We assessed skeletal muscle mass using a bioelectrical impedance analysis at the start of dietary treatment and 12 months after the first assessment. Variables related to muscle reduction were analyzed using a logistic regression model. Results One hundred and eighteen cases were analyzed, excluding those with missing data. In the muscle reduction group, there were more subjects with body weight reduction than in the control group (68% and 40%, respectively, p=0.002), and their body mass index (BMI) was decreased (-0.7 kg/m2 and +0.3 kg/m2, respectively, p=0.0003). There was a significant correlation between the changes in the BMI and muscle mass (R=0.48, p<0.0001). We standardized muscle mass change by dividing it by weight change to analyze the severe decrease in muscle mass compared to weight change. A logistic regression analysis revealed that type 2 diabetes mellitus (T2DM) was an independent variable related to severe skeletal muscle loss (odds ratio, 2.69; 95% CI: 1.13-6.42, p=0.03). Conclusion Weight loss is associated with skeletal muscle loss during dietary treatment for MASLD. T2DM is a risk factor for severe skeletal muscle loss.
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Affiliation(s)
- Akitoshi Sano
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Manami Sasaki
- Department of Nutritional Management, Tohoku University Hospital, Japan
| | - Jun Inoue
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Eiji Kakazu
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
- Department of Liver Disease, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Japan
| | - Masashi Ninomiya
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Mio Tsuruoka
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Kosuke Sato
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Masazumi Onuki
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Satoko Sawahashi
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Keishi Ouchi
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Kotaro Doi
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Yukio Katori
- Department of Nutritional Management, Tohoku University Hospital, Japan
- Division of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
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Real Martinez Y, Fernandez-Garcia CE, Fuertes-Yebra E, Calvo Soto M, Berlana A, Barrios V, Caldas M, Gonzalez Moreno L, Garcia-Buey L, Molina Baena B, Sampedro-Nuñez M, Beceiro MJ, García-Monzón C, González-Rodríguez Á. Assessment of skeletal muscle alterations and circulating myokines in metabolic dysfunction-associated steatotic liver disease: A cross-sectional study. World J Gastroenterol 2025; 31:100039. [PMID: 39991673 PMCID: PMC11755261 DOI: 10.3748/wjg.v31.i7.100039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 12/04/2024] [Accepted: 12/25/2024] [Indexed: 01/20/2025] Open
Abstract
BACKGROUND Skeletal muscle alterations (SMAs) are being increasingly recognized in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and appear to be associated with deleterious outcomes in these patients. However, their actual prevalence and pathophysiology remain to be elucidated. AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD. METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria, recruited from the outpatient clinics of a tertiary level hospital. The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography. Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort. Statistical analysis was performed comparing results according to liver fibrosis and steatosis. RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis. Interestingly, serum levels of fibroblast growth factor-21 (FGF21) were significantly higher in patients with MASLD with advanced hepatic fibrosis (F3-F4) than in those with lower fibrosis stages (F0-F2) (197.49 ± 198.27 pg/mL vs 95.62 ± 83.67 pg/mL; P = 0.049). In addition, patients with MASLD with severe hepatosteatosis (S3) exhibited significantly higher serum levels of irisin (1116.87 ± 1161.86 pg/mL) than those with lower grades (S1-S2) (385.21 ± 375.98 pg/mL; P = 0.001). CONCLUSION SMAs were uncommon in the patients with MASLD studied. Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis, respectively, with potential implications as biomarkers.
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Affiliation(s)
- Yolanda Real Martinez
- Servicio Aparato Digestivo, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain
| | - Carlos Ernesto Fernandez-Garcia
- Unidad de Investigación, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria La Princesa, Madrid 28009, Spain
| | - Esther Fuertes-Yebra
- Unidad de Investigación, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria La Princesa, Madrid 28009, Spain
| | - Mario Calvo Soto
- Servicio Aparato Digestivo, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain
| | - Angela Berlana
- Unidad de Investigación, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria La Princesa, Madrid 28009, Spain
| | - Vicente Barrios
- Department of Endocrinology, Department of Pediatrics, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid 28009, Spain
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Maria Caldas
- Servicio Aparato Digestivo, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain
| | - Leticia Gonzalez Moreno
- Servicio Aparato Digestivo, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain
| | - Luisa Garcia-Buey
- Servicio Aparato Digestivo, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain
| | - Begoña Molina Baena
- Servicio de Endocrinología y Nutrición, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain
| | - Miguel Sampedro-Nuñez
- Servicio de Endocrinología y Nutrición, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain
| | - Maria J Beceiro
- Servicio Aparato Digestivo, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain
| | - C García-Monzón
- Unidad de Investigación, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria La Princesa, Madrid 28009, Spain
| | - Águeda González-Rodríguez
- Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM), CSIC-UAM, Madrid 28029, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Madrid 28029, Spain
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Oliver C, Climstein M, Rosic N, Bosy‐Westphal A, Tinsley G, Myers S. Fat-Free Mass: Friend or Foe to Metabolic Health? J Cachexia Sarcopenia Muscle 2025; 16:e13714. [PMID: 39895188 PMCID: PMC11788497 DOI: 10.1002/jcsm.13714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 11/25/2024] [Accepted: 01/02/2025] [Indexed: 02/04/2025] Open
Abstract
BACKGROUND Fat mass (FM) and fat-free mass (FFM) are body composition estimates commonly reported in research studies and clinical settings. Recently, fat-free mass indexed to height (fat-free mass index; FFMI) has been shown to be positively associated with impaired insulin sensitivity or insulin resistance. Consequently, hypertrophic resistance training which can increase FFM was also questioned. This paper sets out to evaluate these propositions. METHODS In this narrative review, we discuss possible reasons that link FFMI to adverse metabolic health outcomes including the limitations of the body composition model that utilizes FFM. The safety of resistance training is also briefly discussed. RESULTS Approximately 50% of FFM is comprised of skeletal muscle (SM), with the other 50% being viscera, skin, and bone; FFM and SM cannot be conflated. FFM and fat mass (FM) can both rise with increasing body weight and adiposity, indicating a positive correlation between the two compartments. Risk assessment models not adequately adjusting for this correlation may cause erroneous conclusions, however which way FM and FFM are indexed. Adipose tissue accumulation with weight gain, measured by dual-energy X-ray absorptiometry or bioelectrical impedance, can inflate FFM estimates owing to increased connective tissue. Increased adiposity can also result in fat deposition within skeletal muscle disrupting metabolic health. Importantly, non-skeletal muscle components of the FFM, i.e., the liver and pancreas, both critical in metabolic health, can also be negatively affected by the same lifestyle factors that impact SM. The most frequently used body composition techniques used to estimate FM and FFM cannot detect muscle, liver or pancreas fat infiltration. Prospective evidence demonstrates that resistance training is a safe and effective exercise modality across all ages, especially in older adults experiencing age- or disease-related declines in muscle health. CONCLUSIONS The association between FFM and insulin resistance is largely an artefact driven by inadequate assessment of skeletal muscle. If FM and FFM are used, at the minimum, they need to be evaluated in context with one another. Body composition methods, such as magnetic resonance imaging, which measures skeletal muscle rather than fat-free mass, and adipose tissue as well as muscle ectopic fat, are preferred methods. Resistance training is important in achieving and maintaining good health across the lifespan. While strength and power are critical components of resistance training, the reduction of skeletal mass through ageing or disease may require hypertrophic training to mitigate and slow down the progression of this often-inevitable process.
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Affiliation(s)
| | - Mike Climstein
- Clinical and Health ServicesFaculty of HealthSouthern Cross UniversityBilingaQLDAustralia
- Exercise and Sport Science Exercise, Health & Performance Faculty Research GroupFaculty of Health SciencesUniversity of SydneySydneyNSWAustralia
| | - Nedeljka Rosic
- Faculty of HealthSouthern Cross UniversityBilingaQLDAustralia
| | - Anja Bosy‐Westphal
- Institut für Humanernährung und Lebensmittelkunde Christian‐Albrechts‐Universität zu KielKielGermany
| | - Grant Tinsley
- Department of Kinesiology & Sport ManagementTexas Tech UniversityLubbockTexasUSA
| | - Stephen Myers
- Faculty of HealthSouthern Cross UniversityLismoreNSWAustralia
- NatMed‐ResearchEvans HeadNSWAustralia
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Khanmohammadi S, Masrour M, Fallahtafti P, Habibzadeh A, Schuermans A, Kuchay MS. The relationship between nonalcoholic fatty liver disease and frailty: A systematic review and meta-analysis. Diabetes Metab Syndr 2025; 19:103187. [PMID: 39798236 DOI: 10.1016/j.dsx.2025.103187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 01/02/2025] [Accepted: 01/05/2025] [Indexed: 01/15/2025]
Abstract
BACKGROUND AND AIM Frailty is frequently observed in end-stage liver disease of various etiologies, but its role in nonalcoholic fatty liver disease (NAFLD) remains incompletely understood. We aimed to conduct a systematic review and meta-analysis to assess the association and prevalence of frailty in NAFLD. METHODS A systematic review of PubMed/MEDLINE, EMBASE, Web of Science, and Scopus was performed. The random-effects model was used to estimate the pooled prevalence of frailty. Meta-analyzed odds ratios (OR) were calculated to examine the association between frailty and NAFLD. RESULTS Among the initial 430 articles identified, 18 studies were included. Three studies involving 3673 participants had a pooled OR of 2.03 (95% CI: 1.51-2.72; I^2 = 1.1%; p < 0.0001) for the association between frailty and NAFLD. The pooled prevalence of frailty in individuals with NAFLD was 23% (95% CI: 13%-38%; I^2 = 93.5%) using the liver frailty index (LFI) and 8% (95% CI: 3%-21%; I^2 = 98.1%) using the Fried frailty index (FFI). NAFLD patients' mean grip strength and balance time were 26.4 kg (95% CI: 23.0-29.8) and 23s (95% CI: 10-35), respectively. Among studies that also included individuals with liver cirrhosis, grip strength was lower in those with cirrhosis vs. the broader population of those with NAFLD. CONCLUSIONS Our study suggests that frailty is highly prevalent in individuals with NAFLD, with a significantly higher prevalence compared to those without NAFLD. Individuals with NAFLD have more than two-fold increased odds of frailty. Assessing frailty in NAFLD patients enables targeted management to improve outcomes.
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Affiliation(s)
- Shaghayegh Khanmohammadi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahdi Masrour
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Parisa Fallahtafti
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Art Schuermans
- Faculty of Medicine, KU Leuven, Leuven, Belgium; Program in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA, USA
| | - Mohammad Shafi Kuchay
- Division of Endocrinology and Diabetes, Medanta the Medicity Hospital, Gurugram, 122001, Haryana, India.
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Kim HK, Kim DY, Kang S, Kim H, Kim JM, Go GW. Lean metabolic dysfunction-associated steatotic disease is reversed by betulinic acid, a therapeutic triterpene from birch bark. FOOD BIOSCI 2024; 62:104376. [DOI: 10.1016/j.fbio.2024.104376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Chai H, Gao S, Dai Y, Dai J, Zhao G, Zhu J. Association between nutritional status indices and non-alcoholic fatty liver disease in older adults: insights from the National Health and Nutrition Examination Survey 2017-2018. Br J Nutr 2024:1-11. [PMID: 39479899 DOI: 10.1017/s0007114524001442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2024]
Abstract
While previous studies have identified a relationship between dietary intake and the risk of non-alcoholic fatty liver disease (NAFLD), the influence of overall nutritional status on NAFLD development has not been thoroughly investigated. This study sought to explore the association between different nutritional status indicators and NAFLD among the older adults. Nutritional status was evaluated using controlling nutritional status (CONUT), prognostic nutritional index (PNI) and nutritional risk index (GNRI), while NAFLD was identified based on a controlled attenuation parameter ≥ 285 dB/m, measured using transient elastography. The analysis included multivariate regression, receiver operating characteristic analysis, eXtreme Gradient Boosting and subgroup analysis to investigate the relationships between nutritional status indices and NAFLD. The study enrolled 1409 participants for the main analysis, with an NAFLD prevalence of 44·7 %. After accounting for potential confounders, a positive association between PNI and NAFLD was observed. Participants in the third and fourth quartiles of PNI showed increased odds of NAFLD compared with the lowest quartile (Q3: OR = 1·45, 95 % CI (1·03, 2·05); Q4: OR = 2·27, 95 % CI (1·59, 3·24)). Similarly, higher GNRI quartiles were significantly associated with greater odds of NAFLD (Q4 v. Q1: aOR = 1·84; 95 % CI (1·28, 2·65)). Conversely, higher CONUT values were linked to a reduced prevalence of NAFLD (OR = 0·65, 95 % CI (0·48, 0·87)). This study highlights that suboptimal nutritional status, indicating overnutrition as evaluated by PNI, GNRI and CONUT, is positively linked with the risk of NAFLD in individuals aged 50 years and above.
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Affiliation(s)
- Haisheng Chai
- Department of Hepatology, Yueyang Integrated Chinese and Western Medicine Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Sicheng Gao
- Department of Hepatology, Yueyang Integrated Chinese and Western Medicine Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Yaoyao Dai
- Department of Hepatology, Yueyang Integrated Chinese and Western Medicine Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Jinhua Dai
- Department of Hepatology, Yueyang Integrated Chinese and Western Medicine Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Gang Zhao
- Department of Hepatology, Yueyang Integrated Chinese and Western Medicine Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
| | - Junfeng Zhu
- Department of Hepatology, Yueyang Integrated Chinese and Western Medicine Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
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Sheptulina AF, Mamutova EM, Elkina AY, Timofeev YS, Metelskaya VA, Kiselev AR, Drapkina OM. Serum Irisin, Myostatin, and Myonectin Correlate with Metabolic Health Markers, Liver Disease Progression, and Blood Pressure in Patients with Metabolic Dysfunction-Associated Fatty Liver Disease and Hypertension. Metabolites 2024; 14:584. [PMID: 39590820 PMCID: PMC11596689 DOI: 10.3390/metabo14110584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 10/15/2024] [Accepted: 10/25/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND/OBJECTIVES Recent data indicate the involvement of skeletal muscles in the regulation of metabolism and in the pathogenesis of chronic noncommunicable diseases. The goal of our study was to describe the serum concentrations of myokines in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and hypertension (HTN) and their correlation with laboratory parameters, blood pressure (BP), and MASLD severity. METHODS A total of 67 patients with MASLD and HTN underwent anthropometric measurements, laboratory tests, and point shear-wave elastography. The serum concentrations of myokines were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS Patients with detectable serum myonectin concentrations had significantly higher maximum systolic blood pressure (p = 0.022) and higher blood levels of uric acid (p = 0.029). Serum irisin concentration ≥ 6.1 μg/mL was associated with higher FLI values (p = 0.042) and liver stiffness (p = 0.034), as well as with slightly higher waist circumference (p = 0.082) and triglyceride level (p = 0.062). Patients with serum myostatin concentration ≥ 4.98 ng/mL were significantly older (p = 0.033) and had a lower blood albumin level (p = 0.043). CONCLUSIONS In conclusion, the myokine profile in patients with MASLD and HTN correlates both with the severity of MASLD and the parameters characteristic of metabolic health, suggesting the possible contribution of altered irisin, myonectin, and myostatin concentrations to the occurrence of cardiometabolic risks in patients with MASLD.
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Affiliation(s)
- Anna F. Sheptulina
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
- Department of Therapy and Preventive Medicine, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia
| | - Elvira M. Mamutova
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
| | - Anastasia Yu. Elkina
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
- Department of Intermediate Level Therapy, Saratov State Medical University, 410012 Saratov, Russia
| | - Yuriy S. Timofeev
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
| | - Victoria A. Metelskaya
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
| | - Anton R. Kiselev
- Coordinating Center for Fundamental Research, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
| | - Oxana M. Drapkina
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, Russia
- Department of Therapy and Preventive Medicine, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia
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Kang MK, Song JE, Kweon YO, Tak WY, Park SY, Lee YR, Park JG. Visceral Obesity and Its Association with Severe Coronary Artery Calcification in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease. Diagnostics (Basel) 2024; 14:2305. [PMID: 39451628 PMCID: PMC11506773 DOI: 10.3390/diagnostics14202305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 10/15/2024] [Accepted: 10/16/2024] [Indexed: 10/26/2024] Open
Abstract
Background/Objectives: The role of body composition parameters in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) with presence and severity of coronary artery calcification (CAC) is still not fully elucidated. We aimed to evaluate the impact of computed tomography (CT)-based body composition parameters in patients with MASLD with CAC severity. Methods: In this multicenter study, 1870 individuals underwent cardiac CT for the detection of CAC as well as ultrasonography for the diagnosis of hepatic steatosis. The presence of CAC was defined by a CAC score threshold of >0, while severe CAC was defined by a threshold of >300. Using the abdominal cross-sectional CT images at the L3 vertebra level, we analyzed the skeletal muscle index, visceral to subcutaneous adipose tissue ratio, and muscle density using the Hounsfield unit. Results: Of 648 patients with MASLD, the proportions of presence of CAC and severe CAC were 45.2% and 9.9%, respectively. Visceral obesity was not associated with the presence of CAC after adjustment for age, sex, smoking, statin therapy, type 2 diabetes, and advanced fibrosis (adjusted odds ratio (aOR), 1.38; 95% confidence interval (CI), 0.86-2.23; p = 0.180). However, visceral obesity was independently associated with severe CAC after adjustment for several metabolic risk factors (aOR, 3.54; 95% CI, 1.25-14.90; p = 0.039), and adjustment for atherosclerotic cardiovascular disease risk scores (aOR, 3.74; 95% CI, 1.31-15.79; p = 0.032). Conclusions: Visceral obesity may serve as a novel prognostic CT-based radiological biomarker for patients with MASLD with severe CAC.
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Affiliation(s)
- Min Kyu Kang
- Department of Internal Medicine, College of Medicine, Yeungnam University, Daegu 42415, Republic of Korea;
| | - Jeung Eun Song
- Department of Internal Medicine, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea;
| | - Young Oh Kweon
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41994, Republic of Korea; (Y.O.K.); (W.Y.T.); (S.Y.P.)
| | - Won Young Tak
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41994, Republic of Korea; (Y.O.K.); (W.Y.T.); (S.Y.P.)
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41994, Republic of Korea; (Y.O.K.); (W.Y.T.); (S.Y.P.)
| | - Yu Rim Lee
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41994, Republic of Korea; (Y.O.K.); (W.Y.T.); (S.Y.P.)
| | - Jung Gil Park
- Department of Internal Medicine, College of Medicine, Yeungnam University, Daegu 42415, Republic of Korea;
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Long Y, Wu Y, Zhong Y, Wu Y, Ye H, Luo Y, Xiao L, Ma Y, Wang M. Resveratrol as a potential therapeutic agent for sarcopenic obesity: Insights from in vivoperiments. Biomed Pharmacother 2024; 179:117396. [PMID: 39236475 DOI: 10.1016/j.biopha.2024.117396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 08/27/2024] [Accepted: 08/30/2024] [Indexed: 09/07/2024] Open
Abstract
Sarcopenic obesity (SO) is a metabolic disorder with increasing prevalence. It is characterized by a reduction in skeletal muscle mass and strength. Resveratrol (RSV) is one of the most frequently used herbs in the treatment of skeletal muscle atrophy. However, the precise mechanism of the action of RSV in SO remains unclear. The objective of this study was to examine the pharmacological mechanism of RSV in the context of SO through the lens of network pharmacology, to validate these findings through in vivo experimentation. A list of potential RSV targets was compiled by retrieving the data from multiple databases. This list was then cross-referenced with a list of potential targets related to SO. The intersections of RSV- and SO-related targets were analyzed using Venn diagrams. To identify the core genes, a protein-protein interaction (PPI) network of the intersection targets was constructed and subsequently analyzed. Molecular docking was used to predict RSV binding to its core targets. A high-fat diet was used to induce SO in mice. These findings indicated that RSV may prevent SO by acting on 11 targets. Among these, interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor (TNF) are considered core targets. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results indicated that the anti-SO effect of RSV was predominantly linked to metabolic disease-related pathways, including those associated with nonalcoholic fatty liver disease. The anti-inflammatory effects of RSV were confirmed in vivo in an SO mouse model. This study contributes to a more comprehensive understanding of the key mechanisms of the action of RSV against SO and provides new possibilities for drug development in the pathological process of SO.
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Affiliation(s)
- Yi Long
- Department of Rehabilitation, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China
| | - Yi Wu
- Key Laboratory of Mitochondrial Medicine, Key Laboratory of Genetic and Developmental Related Diseases, School of Basic Medicine, Gannan Medical University, Ganzhou 341000, China
| | - Yanbiao Zhong
- Department of Rehabilitation, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China
| | - Yanlin Wu
- Department of Rehabilitation, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China
| | - Hua Ye
- Department of Rehabilitation, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China
| | - Yu Luo
- Department of Rehabilitation, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China
| | - Li Xiao
- Department of Rehabilitation, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China
| | - Yixuan Ma
- Key Laboratory of Mitochondrial Medicine, Key Laboratory of Genetic and Developmental Related Diseases, School of Basic Medicine, Gannan Medical University, Ganzhou 341000, China
| | - Maoyuan Wang
- Department of Rehabilitation, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China.
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10
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Debroy P, Barrett BW, Erlandson KM, Budoff M, Brown TT, Price JC, Post WS, Stosor V, Skavarca C, D’Souza G, Lake JE. Relationships Between Hepatic Steatosis and Frailty Differ by HIV Serostatus. J Acquir Immune Defic Syndr 2024; 97:165-171. [PMID: 39250650 PMCID: PMC11780755 DOI: 10.1097/qai.0000000000003477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 05/16/2024] [Indexed: 09/11/2024]
Abstract
BACKGROUND Frailty is associated with obesity-related comorbidities, but the relationship with nonalcoholic fatty liver disease (NAFLD) in people with HIV has been incompletely described. Our objective was to assess the associations between NAFLD and frailty. METHODS Cross-sectional and longitudinal analysis of men in the Multicenter AIDS Cohort Study. NAFLD was defined as a liver/spleen ratio <1.0 on abdominal computed tomography scans; frailty was defined by the frailty phenotype as having 3 of the following: weakness, slowness, weight loss, exhaustion, and low physical activity. RESULTS Men without (n = 200) and with HIV (n = 292) were included. NAFLD prevalence was 21% vs 16% and frailty 12% vs 17%, respectively. Among men with NAFLD, frailty was more prevalent in men without HIV (21% vs 11%). In multivariate analysis, NAFLD was significantly associated with frailty after controlling for significant variables. Men without HIV and NAFLD had 2.6 times higher probability [95% confidence interval (CI): 1.2- to 5.7] of frailty relative to men with neither HIV nor NAFLD. This association was not seen in men with HIV. The probability of frailty was higher among men without HIV with NAFLD (27% vs 10% in men without NAFLD) but lower among men with HIV with NAFLD (14% vs 19% in men without NAFLD). No significant relationships were found in longitudinal analyses. CONCLUSIONS NAFLD was independently associated with frailty among men without HIV but not men with HIV, despite increased prevalence of frailty among men with HIV. The mechanisms of the muscle-liver-adipose tissue axis underlying NAFLD might differ by HIV serostatus.
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Affiliation(s)
- Paula Debroy
- Division of Infectious Diseases, UTHealth Houston, Houston, TX
| | | | - Kristine M. Erlandson
- Division of Infectious Diseases, University of Colorado Anschutz Medical Center, Aurora, CO
| | | | - Todd T. Brown
- Department of Endocrinology, Johns Hopkins University, Baltimore, MD
| | - Jennifer C. Price
- Division of Hepatology, University of California San Francisco, San Francisco, CA
| | - Wendy S. Post
- Department of Endocrinology, Johns Hopkins University, Baltimore, MD
| | - Valentina Stosor
- Division of Infectious Diseases, Northwestern University, Evanston, IL
| | - Carling Skavarca
- Department of Infectious Diseases and Microbiology University of Pittsburgh, Pittsburgh, PA
| | | | - Jordan E. Lake
- Division of Infectious Diseases, UTHealth Houston, Houston, TX
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11
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Fann Y, Teo W, Lee H, Liao C, Tsay Y, Huang T, Lo J. Regimen on Dnaja3 haploinsufficiency mediated sarcopenic obesity with imbalanced mitochondrial homeostasis and lipid metabolism. J Cachexia Sarcopenia Muscle 2024; 15:2013-2029. [PMID: 39132696 PMCID: PMC11446717 DOI: 10.1002/jcsm.13549] [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: 03/17/2024] [Revised: 06/18/2024] [Accepted: 06/25/2024] [Indexed: 08/13/2024] Open
Abstract
BACKGROUND Sarcopenic obesity is characterized by excess fat mass and diminished muscular mass/function. DNAJA3, a mitochondrial co-chaperone protein, plays a crucial role in skeletal muscle development. GMI, an immunomodulatory protein, promotes myogenic differentiation through DNAJA3 activation. This study aims to elucidate the physiological effects of muscular Dnaja3 haploinsufficiency on mitochondrial dysfunction and dysregulated lipid metabolism and to assess the efficacy of GMI in rescuing sarcopenic obesity both in vitro and in vivo. METHODS We generated mouse strain with Dnaja3 heterozygosity (HSA-Dnaja3f/+) specifically in skeletal muscle. The body weight, body composition, and locomotor activity of WT and HSA-Dnaja3f/+ mice were examined. The isolated skeletal muscles and primary myoblasts from the WT and HSA-Dnaja3f/+ mice, at young or old age, were utilized to study the molecular mechanisms, mitochondrial respiration and ROS level, mitochondrial proteomes, and serological analyses, respectively. To evaluate the therapeutic efficacy of GMI, both short-term and long-term GMI treatment were administrated intraperitoneally to the HSA-Dnaja3f/+ young (4 weeks old) or adult (3 months old) mice for a duration of either 1 or 6 months, respectively. RESULTS Muscular Dnaja3 heterozygosity resulted in impaired locomotor activity (P < 0.05), reduced muscular cross-sectional area (P < 0.0001), and up-regulation of lipogenesis (ACC2) and pro-inflammation (STAT3) in skeletal muscles (P < 0.05). Primary myoblasts from the HSA-Dnaja3f/+ mice displayed impaired mitochondrial respiration (P < 0.01) and imbalanced mitochondrial ROS levels. A systemic proteomic analysis of the purified mitochondria from the primary myoblasts was conducted to show the abnormalities in mitochondrial function and fatty acid metabolism (P < 0.0001). At age of 13 to 14 months, the HSA-Dnaja3f/+ mice displayed increased body fat mass (P < 0.001), reduced fat-free mass (P < 0.01), and impaired glucose and insulin tolerance (P < 0.01). The short-term GMI treatment improved locomotor activity (P < 0.01) and down-regulated the protein levels of STAT3 (P < 0.05), ACC2, and mitochondrial respiratory complex III (UQCRC2) (P < 0.01) via DNAJA3 activation. The long-term GMI treatment ameliorated fat mass accumulation, glucose intolerance, and systemic inflammation (AST) (P < 0.05) in skeletal muscle, while enhancing thermogenesis (UCP1) (P < 0.01) in eWAT. GMI treatment promoted myogenesis, enhanced oxygen consumption, and ameliorated STAT3 (P < 0.01) through DNAJA3 activation (P < 0.05) in vitro. CONCLUSIONS Muscular Dnaja3 haploinsufficiency dysregulates mitochondrial function and lipid metabolism then leads to sarcopenic obesity. GMI emerges as a therapeutic regimen for sarcopenic obesity treatment through DNAJA3 activation.
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Affiliation(s)
- Yu‐Ning Fann
- Institute of Pharmacology, College of MedicineNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Wan‐Huai Teo
- Institute of Oral Biology, College of DentistryNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Hsin‐Chen Lee
- Institute of Pharmacology, College of MedicineNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
- Department of Pharmacy, College of Pharmaceutical SciencesNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Chen‐Chung Liao
- Mass Spectrometry Facility, Instrumentation Resource CenterNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
- Cancer Progression Research CenterNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Yeou‐Guang Tsay
- Institute of Biochemistry and Molecular Biology, College of Life ScienceNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
| | - Tung‐Fu Huang
- School of Medicine, College of MedicineNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
- Department of Orthopedics and TraumatologyTaipei Veterans General HospitalTaipeiTaiwan
| | - Jeng‐Fan Lo
- Institute of Pharmacology, College of MedicineNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
- Institute of Oral Biology, College of DentistryNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
- Cancer Progression Research CenterNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
- Department of Dentistry, College of DentistryNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
- Department of DentistryTaipei Veterans General HospitalTaipeiTaiwan
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12
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Sheptulina AF, Yafarova AA, Mamutova EM, Drapkina OM. Sonographic Features of Rectus Femoris Muscle in Patients with Metabolic Dysfunction-Associated Fatty Liver Disease and Their Correlation with Body Composition Parameters and Muscle Strength: Results of a Single-Center Cross-Sectional Study. Biomedicines 2024; 12:1684. [PMID: 39200149 PMCID: PMC11351426 DOI: 10.3390/biomedicines12081684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 07/15/2024] [Accepted: 07/24/2024] [Indexed: 09/01/2024] Open
Abstract
This study aimed to describe sonographic features of rectus femoris muscle (RFM) in patients with metabolic dysfunction-associated fatty liver disease (MASLD) and their correlation with body composition parameters and muscle strength. A total of 67 patients with MASLD underwent dual-energy X-ray absorptiometry (DEXA), bioimpedance analysis (BIA), muscle strength measurement (grip strength [GS] and chair stand test [CST]), and ultrasound (US) investigation of the RFM in the dominant thigh using a 4 to 18 MHz linear probe. MASLD patients exhibited increased RFM echogenicity, possibly due to fatty infiltration. We confirmed that the greater the subcutaneous fat thickness, the smaller was the muscle mass (p < 0.001), and the lower was the muscle strength (p < 0.001 for GS and p = 0.002 for CST). On the contrary, the greater the anteroposterior diameter (APD) of RFM, the higher was the muscle mass (p < 0.001), and the greater was the muscle strength (p < 0.001 for GS and p = 0.007 for CST). In addition, APD of the RFM and stiffness of RFM exhibited direct correlation with bone mineral density values of the lumbar spine (p = 0.005 for both GS and CST). We concluded that US investigation of the RFM in the dominant thigh can be helpful in identifying MASLD patients at a high risk of musculoskeletal disorders given repeated point-of-care clinical evaluations.
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Affiliation(s)
- Anna F. Sheptulina
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, Moscow 101990, Russia; (A.A.Y.); (E.M.M.); (O.M.D.)
| | - Adel A. Yafarova
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, Moscow 101990, Russia; (A.A.Y.); (E.M.M.); (O.M.D.)
| | - Elvira M. Mamutova
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, Moscow 101990, Russia; (A.A.Y.); (E.M.M.); (O.M.D.)
| | - Oxana M. Drapkina
- Department of Fundamental and Applied Aspects of Obesity, National Medical Research Center for Therapy and Preventive Medicine, Moscow 101990, Russia; (A.A.Y.); (E.M.M.); (O.M.D.)
- Department of Therapy and Preventive Medicine, A.I. Evdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
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Gerrard SD, Biase FH, Yonke JA, Yadav R, Shafron AJ, Sunny NE, Gerrard DE, El-Kadi SW. Non-Alcoholic Fatty Liver Disease Induced by Feeding Medium-Chain Fatty Acids Upregulates Cholesterol and Lipid Homeostatic Genes in Skeletal Muscle of Neonatal Pigs. Metabolites 2024; 14:384. [PMID: 39057707 PMCID: PMC11278539 DOI: 10.3390/metabo14070384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 07/05/2024] [Accepted: 07/08/2024] [Indexed: 07/28/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a range of disorders characterized by lipid accumulation in hepatocytes. Although this spectrum of disorders is associated with adult obesity, recent evidence suggests that this condition could also occur independently of obesity, even in children. Previously, we reported that pigs fed a formula containing medium-chain fatty acids (MCFAs) developed hepatic steatosis and weighed less than those fed an isocaloric formula containing long-chain fatty acids (LCFAs). Our objective was to determine the association between NAFLD and the skeletal muscle transcriptome in response to energy and lipid intake. Neonatal pigs were fed one of three formulas: a control formula (CONT, n = 6) or one of two isocaloric high-energy formulas containing either long (LCFA, n = 6) or medium (MCFA, n = 6) chain fatty acids. Pigs were fed for 22 d, and tissues were collected. Body weight at 20 and 22 d was greater for LCFA-fed pigs than their CONT or MCFA counterparts (p < 0.005). Longissimus dorsi weight was greater for LCFA compared with MCFA, while CONT was intermediate (p < 0.05). Lean gain and protein deposition were greater for LCFA than for CONT and MCFA groups (p < 0.01). Transcriptomic analysis revealed 36 differentially expressed genes (DEGs) between MCFA and LCFA, 53 DEGs between MCFA and CONT, and 52 DEGs between LCFA and CONT (FDR < 0.2). Feeding formula high in MCFAs resulted in lower body and muscle weights. Transcriptomics data suggest that the reduction in growth was associated with a disruption in cholesterol metabolism in skeletal muscles.
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Affiliation(s)
- Samuel D. Gerrard
- School of Animal Sciences, Virginia Tech, Blacksburg, VA 24601, USA; (S.D.G.); (F.H.B.); (J.A.Y.); (R.Y.); (A.J.S.); (D.E.G.)
| | - Fernando H. Biase
- School of Animal Sciences, Virginia Tech, Blacksburg, VA 24601, USA; (S.D.G.); (F.H.B.); (J.A.Y.); (R.Y.); (A.J.S.); (D.E.G.)
| | - Joseph A. Yonke
- School of Animal Sciences, Virginia Tech, Blacksburg, VA 24601, USA; (S.D.G.); (F.H.B.); (J.A.Y.); (R.Y.); (A.J.S.); (D.E.G.)
| | - Ravi Yadav
- School of Animal Sciences, Virginia Tech, Blacksburg, VA 24601, USA; (S.D.G.); (F.H.B.); (J.A.Y.); (R.Y.); (A.J.S.); (D.E.G.)
| | - Anthony J. Shafron
- School of Animal Sciences, Virginia Tech, Blacksburg, VA 24601, USA; (S.D.G.); (F.H.B.); (J.A.Y.); (R.Y.); (A.J.S.); (D.E.G.)
| | - Nishanth E. Sunny
- Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA;
| | - David E. Gerrard
- School of Animal Sciences, Virginia Tech, Blacksburg, VA 24601, USA; (S.D.G.); (F.H.B.); (J.A.Y.); (R.Y.); (A.J.S.); (D.E.G.)
| | - Samer W. El-Kadi
- School of Animal Sciences, Virginia Tech, Blacksburg, VA 24601, USA; (S.D.G.); (F.H.B.); (J.A.Y.); (R.Y.); (A.J.S.); (D.E.G.)
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14
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Yan C, Zhang W, Xiao Y, Sun Y, Peng X, Cai W. The predictive role of the platelet-to-lymphocyte ratio for the risk of non-alcoholic fatty liver disease and cirrhosis: a nationwide cross-sectional study. Front Endocrinol (Lausanne) 2024; 15:1376894. [PMID: 39040676 PMCID: PMC11260703 DOI: 10.3389/fendo.2024.1376894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Accepted: 06/17/2024] [Indexed: 07/24/2024] Open
Abstract
Background The associations between platelet-to-lymphocyte ratio (PLR) and non-alcoholic fatty liver disease (NAFLD) and cirrhosis are unclear, and there are still no effective means for diagnosing or monitoring disease progression. Methods Data from the National Health and Nutrition Examination Surveys were collected for analysis. Logistic regression and restricted cubic splines were used to evaluate the associations between PLR and NAFLD and cirrhosis in different populations. The Area Under Curve Receiver Operating Characteristic (AUCROC) was used to distinguish the models. Threshold analysis was performed by constructing a two-piecewise linear regression. Correlation analysis was performed separately on either side of the inflection point. Results A total of 5724 adults were included. Logistic regression analysis revealed that the PLR was associated with NAFLD and cirrhosis (AUCROC of NAFLD: 0.803; AUCROC of cirrhosis: 0.851). The AUCROC of the PLR for predicting NAFLD incidence was 0.762 in the diabetic population and 0.804 in the nondiabetic population. High PLR predicted cirrhosis in the diabetic population, with an AUCROC of 0.824, whereas a high PLR was not associated with cirrhosis in the nondiabetic population. The restricted cubic spline revealed a negative linear correlation between the PLR and NAFLD incidence. The inflection point of the PLR for NAFLD was 180.74. A PLR ≤180.74 was statistically significant (odds ratio=0.997, 95% confidence interval=0.995-0.999). In the NAFLD population, the PLR was negatively correlated with cirrhosis at a PLR ≤130.5 (odds ratio=0.987, 95% confidence interval=0.977-0.996) and positively correlated with cirrhosis at a PLR > 130.5 (odds ratio=1.006, 95% confidence interval=1.001-1.012). Conclusions The PLR and NAFLD were negatively correlated in the U.S. population. The PLR had a U-shaped relationship with cirrhosis in the NAFLD population. The PLR has potential value in monitoring NAFLD patient progression to cirrhosis.
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Affiliation(s)
- Cheng Yan
- Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Weichang Zhang
- Department of Vascular Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yangyan Xiao
- Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yuxin Sun
- Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Xinke Peng
- Department of Rehabilitation, The First Affiliated Hospital of Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Wenwu Cai
- Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
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15
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Huang M, Xu B, Xu Y, Zhang K, Zhu W, Lian X, Chen Z, Wang M, Liu L, Guo Z. Serum iron level is independently associated with sarcopenia: a retrospective study. Sci Rep 2024; 14:10554. [PMID: 38719903 PMCID: PMC11078979 DOI: 10.1038/s41598-024-61429-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Accepted: 05/06/2024] [Indexed: 05/12/2024] Open
Abstract
Sarcopenia greatly reduces the quality of life of the elderly, and iron metabolism plays an important role in muscle loss. This study aimed to investigate the association between iron status and sarcopenia. A total of 286 adult patients hospitalized between 2019 and 2021 were included in this study, of which 117 were diagnosed with sarcopenia. Serum iron, total iron binding capacity (TIBC), transferrin, and transferrin saturation levels were compared between groups with and without sarcopenia and were included in the logistic analyses, with significant variables further included in the logistic regression model for the prediction of sarcopenia. Serum iron, TIBC, and transferrin levels decreased significantly in the sarcopenia group (p < 0.05), and were negatively associated with handgrip strength, relative skeletal muscle index, and multiple test performances (p < 0.05). Multivariate logistic analysis showed that sex, age, body mass index (BMI), and serum iron level were independent risk factors for sarcopenia. In the final logistic regression model, male sex (odds ratio [OR] 3.65, 95% confidence interval [CI] 1.67-7.98), age > 65 years (OR 5.40, 95% CI 2.25-12.95), BMI < 24 kg/m2 (OR 0.17, 95% CI 0.08-0.36), and serum iron < 10.95 μmol/L (OR 0.39, 95% CI 0.16-0.93) were included. Our study supported the impact of iron metabolism on muscle strength and performance.
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Affiliation(s)
- Meiying Huang
- Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Bingqing Xu
- Department of Gerontology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, 215300, Jiangsu, China
| | - Yihui Xu
- Department of Gerontology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, 215300, Jiangsu, China
| | - Kaiyu Zhang
- Department of Gerontology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, 215300, Jiangsu, China
| | - Wenyu Zhu
- Department of Gerontology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, 215300, Jiangsu, China
| | - Xiaoyi Lian
- Department of Gerontology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, 215300, Jiangsu, China
| | - Zhe Chen
- Laboratory of Cough, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, Jiangsu, China
| | - Minhong Wang
- Department of Gerontology, Suzhou Municipal Hospital, Suzhou, 215300, Jiangsu, China
| | - Lei Liu
- Department of Gerontology, Suzhou Municipal Hospital, Suzhou, 215300, Jiangsu, China.
| | - Zhengli Guo
- Department of Gerontology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, 215300, Jiangsu, China.
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Rho HS, Choi WS. Low Muscle Strength as Risk Factor for Non-Alcoholic Fatty Liver Disease in Different Metabolic Conditions. Korean J Fam Med 2024; 45:89-95. [PMID: 38012004 DOI: 10.4082/kjfm.23.0118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 09/26/2023] [Indexed: 11/29/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) recently became a leading liver disease that threatens health worldwide. Low muscle strength, obesity, insulin resistance, and metabolic syndrome are recognized key factors for NAFLD. However, the impact of low muscle strength itself in different metabolic conditions has not been widely studied. METHODS A cross-sectional analysis was performed of a sample of 5,427 participants from the 2019 Korea National Health and Nutrition Examination Survey. Relative handgrip strength (rHGS, defined as handgrip strength/body mass index) was used to assess muscle strength. The cut-off values for a low rHGS were 1.405 for men and 0.850 for women. NAFLD was diagnosed if the Hepatic Steatosis Index was >36. Participants were stratified according to insulin resistance, metabolic syndrome, and central obesity for the subgroup analyses. RESULTS Complex sample multivariate logistic regression analysis revealed a significant association between low muscle strength and NAFLD after the adjustment for other confounders (odds ratio [OR], 1.92; P<0.001). In the insulin resistance, metabolic syndrome, and central obesity subgroups, a significant association between low muscle strength and NAFLD remained (OR, 1.66-4.19 depending on subgroup; all P<0.05), whereas it did not in the no central obesity group. CONCLUSION This study demonstrated that low muscle strength is correlated with a risk of NAFLD. This relationship was independent of insulin resistance and metabolic syndrome but was dependent on the presence of central obesity.
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Affiliation(s)
- Hye-Sun Rho
- Department of Family Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Whan-Seok Choi
- Department of Family Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Atabieke F, Li XJ, Aierken A, Li J, Zhang Y, Aizezi Y, Gao HL, Zhang ZQ. Association between frailty and hepatic fibrosis in NAFLD among middle-aged and older adults: results from NHANES 2017-2020. Front Public Health 2024; 12:1330221. [PMID: 38389936 PMCID: PMC10883311 DOI: 10.3389/fpubh.2024.1330221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Accepted: 01/29/2024] [Indexed: 02/24/2024] Open
Abstract
Background Although previous studies found that frailty is prevalent in NAFLD patients with advanced liver fibrosis and cirrhosis, studies examining the relationship are spare. Aim Our study aspires to investigate the potential correlation between the Frailty Index (FI) and hepatic fibrosis among middle-aged and older adults with NAFLD. Methods Data from the 2017-2020.03 National Health and Nutrition Examination Survey (NHANES) were utilized for this study, with a final of 2,383 participants aged 50 years and older included. The quantification of frailty was executed employing a 49-item frailty index. The recognition of hepatic steatosis and fibrosis was accomplished through the utilization of the controlling attenuation parameter (CAP) and transient elastography (TE). The relationship between the FI and hepatic fibrosis were investigated employing univariable and multivariable-adjusted logistic regression analyses. A subgroup analysis was conducted, dividing the subjects based on gender, Body Mass Index (BMI), and the presence of hyperlipidemia. Results The findings demonstrated a positive correlation between the FI and significant hepatic fibrosis in NAFLD, even after using multivariate logistic regression models adjusting for potential confounding factors (OR = 1.022, 95% CI, 1.004-1.041) and in tertiles (Q3vs Q1: OR = 2.004, 95% CI, 1.162-3.455). In the subgroup analysis, the correlation was more statistically significant in male (OR = 1.046, 95% CI, 1.022-1.071), under/normal weight (OR = 1.077, 95% CI, 1.009-1.150), overweight (OR = 1.040, 95% CI, 1.010-1.071), and subjects without hyperlipidemia (OR = 1.054, 95% CI, 1.012-1.097). The area under the Receiver Operating Characteristic (ROC) curve for the FI in assessing the existence of substantial fibrosis in NAFLD was 0.612 (95% CI, 0.596-0.628). Conclusion This study demonstrated a positive correlation between significant hepatic fibrosis and frailty, particularly among males aged 50 years and older, who were non-obese and did not have hyperlipidemia with NAFLD. Additional studies are required to further validate these findings.
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Affiliation(s)
- Falide Atabieke
- The Second Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Xiu-Juan Li
- Department of Pathophysiology, School of Basic Medical Sciences Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Ailikamu Aierken
- Xinjiang Medical University School of Clinical Medicine, Children's Hospital of the Autonomous Region, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Jian Li
- The Second Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Yu Zhang
- The Second Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Yierzhati Aizezi
- Center of Critical Care Medicine, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Hong-Liang Gao
- The Second Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Zhi-Qiang Zhang
- The Second Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
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Chrysavgis L, Adamantou M, Angelousi A, Cholongitas E. The association of testosterone with sarcopenia and frailty in chronic liver disease. Eur J Clin Invest 2024; 54:e14108. [PMID: 37837304 DOI: 10.1111/eci.14108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 09/11/2023] [Accepted: 10/06/2023] [Indexed: 10/15/2023]
Abstract
BACKGROUND Testosterone is an important anabolic hormone responsible for maintaining body composition and muscle mass and circulates mostly albumin-bound, or sex hormone binding globulin (SHBG)-bound or free in the plasma. Of these fractions, the latter is bioactive and exerts the androgenic effects on male population. Liver cirrhosis, the advanced stage of any chronic liver disease characterized by permanent distortions to the hepatic architecture, disrupts the hypothalamic-pituitary-gonadal axis, leading to diminished levels of free testosterone and hypogonadism. METHODS We retrieved the PubMed database to provide a synopsis of testosterone's physiology and action and summarize the effect of sarcopenia in pre-cirrhotic and cirrhotic patients. Moreover, we scoped to provide insight into the relationship of testosterone levels with sarcopenia, frailty and survival in cirrhotic and non-cirrhotic population as well as to discuss the efficacy of exogenous testosterone supplementation on the anthropometric parameters and survival of those patients. RESULTS Low testosterone levels have been associated with sarcopenia, reduced body lean mass, decreased bone mineral density and frailty, thus leading to increased morbidity and mortality especially among cirrhotic patients. Furthermore, exogenous testosterone administration significantly ameliorated body composition on patients with chronic hepatic disease, without significant adverse effects. However, the current literature does not suggest any significant effect on survival of those patients. Moreover, the long-term safety of testosterone use remains an open question. CONCLUSION Low serum testosterone is strongly correlated with sarcopenia, frailty, higher rate of hepatic decompensation and mortality. Nonetheless, exogenous supplementation of testosterone did not ameliorate the liver-related outcomes and complications.
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Affiliation(s)
- Lampros Chrysavgis
- First Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Magdalini Adamantou
- First Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Anna Angelousi
- First Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
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19
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Luengo-Pérez LM, Fernández-Bueso M, Ambrojo A, Guijarro M, Ferreira AC, Pereira-da-Silva L, Moreira-Rosário A, Faria A, Calhau C, Daly A, MacDonald A, Rocha JC. Body Composition Evaluation and Clinical Markers of Cardiometabolic Risk in Patients with Phenylketonuria. Nutrients 2023; 15:5133. [PMID: 38140392 PMCID: PMC10745907 DOI: 10.3390/nu15245133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 12/07/2023] [Accepted: 12/11/2023] [Indexed: 12/24/2023] Open
Abstract
Cardiovascular diseases are the main cause of mortality worldwide. Patients with phenylketonuria (PKU) may be at increased cardiovascular risk. This review provides an overview of clinical and metabolic cardiovascular risk factors, explores the connections between body composition (including fat mass and ectopic fat) and cardiovascular risk, and examines various methods for evaluating body composition. It particularly focuses on nutritional ultrasound, given its emerging availability and practical utility in clinical settings. Possible causes of increased cardiometabolic risk in PKU are also explored, including an increased intake of carbohydrates, chronic exposure to amino acids, and characteristics of microbiota. It is important to evaluate cardiovascular risk factors and body composition in patients with PKU. We suggest systematic monitoring of body composition to develop nutritional management and hydration strategies to optimize performance within the limits of nutritional therapy.
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Affiliation(s)
- Luis M. Luengo-Pérez
- Biomedical Sciences Department, University of Extremadura, 06008 Badajoz, Spain
- Clinical Nutrition and Dietetics Unit, Badajoz University Hospital, 06008 Badajoz, Spain; (M.F.-B.); (A.A.); (M.G.)
| | - Mercedes Fernández-Bueso
- Clinical Nutrition and Dietetics Unit, Badajoz University Hospital, 06008 Badajoz, Spain; (M.F.-B.); (A.A.); (M.G.)
| | - Ana Ambrojo
- Clinical Nutrition and Dietetics Unit, Badajoz University Hospital, 06008 Badajoz, Spain; (M.F.-B.); (A.A.); (M.G.)
| | - Marta Guijarro
- Clinical Nutrition and Dietetics Unit, Badajoz University Hospital, 06008 Badajoz, Spain; (M.F.-B.); (A.A.); (M.G.)
| | - Ana Cristina Ferreira
- Reference Centre of Inherited Metabolic Diseases, Centro Hospitalar Universitário de Lisboa Central, Rua Jacinta Marto, 1169-045 Lisboa, Portugal; (A.C.F.); or (J.C.R.)
| | - Luís Pereira-da-Silva
- CHRC—Comprehensive Health Research Centre, Nutrition Group, NOVA Medical School, Universidade Nova de Lisboa, 1349-008 Lisboa, Portugal; (L.P.-d.-S.); (A.F.)
- NOVA Medical School (NMS), Faculdade de Ciências Médicas (FCM), Universidade NOVA de Lisboa, Campo Mártires da Pátria 130, 1169-056 Lisboa, Portugal; (A.M.-R.); (C.C.)
| | - André Moreira-Rosário
- NOVA Medical School (NMS), Faculdade de Ciências Médicas (FCM), Universidade NOVA de Lisboa, Campo Mártires da Pátria 130, 1169-056 Lisboa, Portugal; (A.M.-R.); (C.C.)
- CINTESIS@RISE, Nutrition and Metabolism, NOVA Medical School (NMS), Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Campo Mártires da Pátria 130, 1169-056 Lisboa, Portugal
| | - Ana Faria
- CHRC—Comprehensive Health Research Centre, Nutrition Group, NOVA Medical School, Universidade Nova de Lisboa, 1349-008 Lisboa, Portugal; (L.P.-d.-S.); (A.F.)
- CINTESIS@RISE, Nutrition and Metabolism, NOVA Medical School (NMS), Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Campo Mártires da Pátria 130, 1169-056 Lisboa, Portugal
| | - Conceição Calhau
- NOVA Medical School (NMS), Faculdade de Ciências Médicas (FCM), Universidade NOVA de Lisboa, Campo Mártires da Pátria 130, 1169-056 Lisboa, Portugal; (A.M.-R.); (C.C.)
- CINTESIS@RISE, Nutrition and Metabolism, NOVA Medical School (NMS), Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Campo Mártires da Pátria 130, 1169-056 Lisboa, Portugal
| | - Anne Daly
- Birmingham Children’s Hospital, Birmingham B4 6NH, UK; (A.D.); (A.M.)
| | - Anita MacDonald
- Birmingham Children’s Hospital, Birmingham B4 6NH, UK; (A.D.); (A.M.)
| | - Júlio César Rocha
- Reference Centre of Inherited Metabolic Diseases, Centro Hospitalar Universitário de Lisboa Central, Rua Jacinta Marto, 1169-045 Lisboa, Portugal; (A.C.F.); or (J.C.R.)
- NOVA Medical School (NMS), Faculdade de Ciências Médicas (FCM), Universidade NOVA de Lisboa, Campo Mártires da Pátria 130, 1169-056 Lisboa, Portugal; (A.M.-R.); (C.C.)
- CINTESIS@RISE, Nutrition and Metabolism, NOVA Medical School (NMS), Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Campo Mártires da Pátria 130, 1169-056 Lisboa, Portugal
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20
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Sadeghi A, Niknam M, Momeni-Moghaddam MA, Shabani M, Aria H, Bastin A, Teimouri M, Meshkani R, Akbari H. Crosstalk between autophagy and insulin resistance: evidence from different tissues. Eur J Med Res 2023; 28:456. [PMID: 37876013 PMCID: PMC10599071 DOI: 10.1186/s40001-023-01424-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 10/03/2023] [Indexed: 10/26/2023] Open
Abstract
Insulin is a critical hormone that promotes energy storage in various tissues, as well as anabolic functions. Insulin resistance significantly reduces these responses, resulting in pathological conditions, such as obesity and type 2 diabetes mellitus (T2DM). The management of insulin resistance requires better knowledge of its pathophysiological mechanisms to prevent secondary complications, such as cardiovascular diseases (CVDs). Recent evidence regarding the etiological mechanisms behind insulin resistance emphasizes the role of energy imbalance and neurohormonal dysregulation, both of which are closely regulated by autophagy. Autophagy is a conserved process that maintains homeostasis in cells. Accordingly, autophagy abnormalities have been linked to a variety of metabolic disorders, including insulin resistance, T2DM, obesity, and CVDs. Thus, there may be a link between autophagy and insulin resistance. Therefore, the interaction between autophagy and insulin function will be examined in this review, particularly in insulin-responsive tissues, such as adipose tissue, liver, and skeletal muscle.
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Affiliation(s)
- Asie Sadeghi
- Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran
- Department of Clinical Biochemistry, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Maryam Niknam
- Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Maryam Shabani
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamid Aria
- Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Alireza Bastin
- Clinical Research Development Center "The Persian Gulf Martyrs" Hospital, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Maryam Teimouri
- Department of Biochemistry, School of Allied Medical Sciences, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Reza Meshkani
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamed Akbari
- Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran.
- Department of Clinical Biochemistry, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
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21
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Polyzos SA, Vachliotis ID, Mantzoros CS. Sarcopenia, sarcopenic obesity and nonalcoholic fatty liver disease. Metabolism 2023; 147:155676. [PMID: 37544590 DOI: 10.1016/j.metabol.2023.155676] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 07/29/2023] [Accepted: 08/01/2023] [Indexed: 08/08/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD), sarcopenia and sarcopenic obesity (SO) are highly prevalent conditions that may coexist, especially in the aging population, without any approved pharmacologic treatment for all of them. There are multiple pathophysiologic mechanisms suggested to explain an association between NAFLD and sarcopenia or SO, including alterations in the adipokines, cytokines, hepatokines and myokines, which may interplay with other factors, such as aging, diet and physical inactivity. In clinical terms, most observational studies support an association between NAFLD and sarcopenia or SO; importantly, there are few cohort studies indicating higher mortality in patients with NAFLD and sarcopenia. Their association also bears some treatment considerations: for example, pioglitazone or vitamin E, suggested as off label treatment for selected patients with nonalcoholic steatohepatitis, may be recommended in the coexistence of sarcopenia or SO, since limited evidence did not show adverse effects of them on sarcopenia and abdominal obesity. In this review, evidence linking sarcopenia and SO with NAFLD is summarized, with a special focus on clinical data. A synopsis of the major pathophysiological links between NAFLD and sarcopenia/SO is initially presented, followed by selected clinical studies and, finally, treatment considerations in patients with NAFLD and sarcopenia or SO are discussed.
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Affiliation(s)
- Stergios A Polyzos
- First Department of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
| | - Ilias D Vachliotis
- First Department of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Christos S Mantzoros
- Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Internal Medicine, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA
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22
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Choudhuri G, Shah S, Kulkarni A, Jagtap N, Gaonkar P, Desai A, Adhav C. Non-alcoholic Steatohepatitis in Asians: Current Perspectives and Future Directions. Cureus 2023; 15:e42852. [PMID: 37664266 PMCID: PMC10473263 DOI: 10.7759/cureus.42852] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/01/2023] [Indexed: 09/05/2023] Open
Abstract
Non-alcoholic steatohepatitis (NASH) is a subset of non-alcoholic fatty liver disease (NAFLD), which, apart from excess fat in the liver, may be characterised by some level of inflammatory infiltration and fibrogenesis, occasionally progressing to liver cirrhosis or hepatocellular carcinoma (HCC). The objective of the current review is to elucidate the rising prevalence, the role of microbiome and genetics in pathogenesis, diagnostic challenges, and novel treatment alternatives for NASH. Newer diagnostic techniques are being developed since using liver biopsy in a larger population is not a reasonable option and is primarily restricted to clinical research, at least in developing countries. Besides these technical challenges, another important factor leading to deviation from guideline practice is the lack of health insurance coverage in countries like India. It leads to reluctance on the part of physicians and patients to delay required tests to curb out-of-pocket expenditure. There is no cure for NASH, with liver transplantation remaining the last option for those who progress to end-stage liver disease (ESLD) or are detected with early-stage HCC. Thus, lifestyle modification remains the only viable option for many, but compliance and long-term adherence remain major challenges. In obese individuals, bariatric surgery and weight reduction have shown favourable results. In patients with less severe obesity, endoscopic bariatric metabolic therapies (EBMT) are rapidly emerging as less invasive therapies. However, access and acceptability remain poor for these weight reduction methods. Therefore, intense research is being conducted for potential newer drug classes with several agents currently in phase II or III of clinical development. Some of these have demonstrated promising results, such as a reduction in hepatic fat content, and attenuation of fibrosis with an acceptable tolerability profile in phase II studies. The developments in the management of NASH have been fairly encouraging. Further well-designed long-term prospective studies should be undertaken to generate evidence with definitive results.
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Affiliation(s)
| | - Saumin Shah
- Gastroenterology, Gujarat Gastro and Vascular Hospital, Surat, IND
| | - Anand Kulkarni
- Gastroenterology and Hepatology, Asian Institute of Gastroenterology, Hyderabad, IND
| | - Nitin Jagtap
- Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, IND
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23
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Kim TH, Jeong CW, Lee C, Noh S, Lim DW, Kim JW, Kim HJ, Kim YR. Association between Body Composition Contents and Hepatic Fibrosis in Sarcopenic Obesity. J Clin Med 2023; 12:4279. [PMID: 37445314 DOI: 10.3390/jcm12134279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 06/20/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
It is well established that sarcopenic obesity (SO) is linked to many diseases such as metabolic and non-alcoholic fatty liver diseases, but there is little known about the relationship between SO and hepatic fibrosis progression in chronic liver disease. This study compared body composition contents in patients with non-obesity (NOb) and SO using abdominal magnetic resonance imaging and investigated the relationship between hepatic fibrosis and SO factors. This retrospective study enrolled 60 patients (28 NOb; 32 SO) from June 2014 to December 2020. Patients underwent histopathologic investigation where they classified fibrosis stages based on the Meta-analysis of Histological Data in Viral Hepatitis fibrosis scoring system. Muscle and fat areas at the third lumber vertebra level were assessed. The variation in the areas of muscle (MA), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) among fibrosis stages, and associations between hepatic fibrosis and SO factors, were analyzed. There were significant differences in SAT and VAT (p < 0.001), whereas there was no difference in MA (p = 0.064). There were significant differences in MA/SAT (p = 0.009), MA/VAT (p < 0.001), and MA/(SAT+VAT) (p < 0.001). In all the patients, hepatic fibrosis positively correlated with serum aspartate aminotransferase level (AST, R = 0.324; p = 0.025). Especially in SO patients, hepatic fibrosis closely correlated with body mass index (BMI, R = 0.443; p = 0.011), AST (R = 0.415; p = 0.044), VAT (R = 0.653; p < 0.001), MA/VAT (R = -0.605; p < 0.001), and MA/(SAT+VAT) (R = -0.416; p = 0.018). However, there was no association in NOb patients. This study demonstrated that SO patients had larger SAT and VAT than NOb patients. Hepatic fibrosis in SO positively correlated with body visceral fat composition in combination with BMI and AST level. These findings will be useful for understanding the relationship between the hepatic manifestation of fibrosis and body fat composition in sarcopenia and SO.
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Affiliation(s)
- Tae-Hoon Kim
- Medical Convergence Research Center, Wonkwang University, Wonkwang University Hospital, Iksan 54538, Republic of Korea
| | - Chang-Won Jeong
- Medical Convergence Research Center, Wonkwang University, Wonkwang University Hospital, Iksan 54538, Republic of Korea
| | - ChungSub Lee
- Medical Convergence Research Center, Wonkwang University, Wonkwang University Hospital, Iksan 54538, Republic of Korea
| | - SiHyeong Noh
- Medical Convergence Research Center, Wonkwang University, Wonkwang University Hospital, Iksan 54538, Republic of Korea
| | - Dong Wook Lim
- Medical Convergence Research Center, Wonkwang University, Wonkwang University Hospital, Iksan 54538, Republic of Korea
| | - Jin Woong Kim
- Department of Radiology, Chosun University Hospital of Medicine, Chosun University College, Gwangju 61453, Republic of Korea
| | - Hyung Joong Kim
- Department of Biomedical Engineering, Kyung Hee University, Dongdaemun-gu, Seoul 02447, Republic of Korea
| | - Youe Ree Kim
- Department of Radiology, Wonkwang University Hospital, Wonkwang University School of Medicine, Iksan 54538, Republic of Korea
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24
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Mátis D, Hegyi P, Teutsch B, Tornai T, Erőss B, Pár G, Váncsa S. Improved body composition decreases the fat content in non-alcoholic fatty liver disease, a meta-analysis and systematic review of longitudinal studies. Front Med (Lausanne) 2023; 10:1114836. [PMID: 37215704 PMCID: PMC10194653 DOI: 10.3389/fmed.2023.1114836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 04/13/2023] [Indexed: 05/24/2023] Open
Abstract
Background Based on cross-sectional studies, there is a link between body composition parameters and steatosis in non-alcoholic fatty liver disease (NAFLD). However, whether long-term changes in different body composition parameters will result in NAFLD resolution is unclear. Therefore, we aimed to summarize the literature on longitudinal studies evaluating the association between NAFLD resolution and body composition change. Methods Based on the recommendations of the Cochrane Handbook, we performed a systematic search on September 26th, 2021, in three databases: Embase, MEDLINE (via PubMed), and Cochrane Central Register of Controlled Trials (CENTRAL). Eligible studies reported on patients with NAFLD (liver fat >5%) and examined the correlation between body composition improvement and decrease in steatosis. We did not have pre-defined body composition or steatosis measurement criteria. Next, we calculated pooled correlation coefficient (r) with a 95% confidence interval (CI). Furthermore, we narratively summarized articles with other statistical methods. Results We included 15 studies in our narrative review and five in our quantitative synthesis. Based on two studies with 85 patients, we found a pooled correlation coefficient of r = 0.49 (CI: 0.22-0.69, Spearman's correlation) between the change of visceral adipose tissue and liver steatosis. Similarly, based on three studies with 175 patients, the correlation was r = 0.33 (CI: 0.19-0.46, Pearson's correlation). On the other hand, based on two studies with 163 patients, the correlation between subcutaneous adipose tissue change and liver steatosis change was r = 0.42 (CI: 0.29-0.54, Pearson's correlation). Furthermore, based on the studies in the narrative synthesis, body composition improvement was associated with steatosis resolution. Conclusions Based on the included studies, body composition improvement may be associated with a decrease in liver fat content in NAFLD. Systematic review registration Identifier: CRD42021278584.
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Affiliation(s)
- Dóra Mátis
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Péter Hegyi
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Brigitta Teutsch
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Tamás Tornai
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Bálint Erőss
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Gabriella Pár
- Division of Gastroenterology, First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - Szilárd Váncsa
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
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25
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Muriel P, Cardoso-Lezama I, Vargas-Pozada EE, Ramos-Tovar E. Mechanisms of non-alcoholic fatty liver disease development in normal-weight individuals. Eur J Gastroenterol Hepatol 2023; 35:521-529. [PMID: 36966767 DOI: 10.1097/meg.0000000000002530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/30/2023]
Abstract
While non-alcoholic fatty liver disease (NAFLD) without inflammation or fibrosis is considered a relatively 'benign' disease, non-alcoholic steatohepatitis (NASH), by contrast, is characterized by marked inflammation in addition to lipid accumulation, and may include fibrosis, progression to cirrhosis and hepatocellular carcinoma. Obesity and type II diabetes are frequently associated with NAFLD/NASH; however, a significant number of lean individuals may develop these diseases. Little attention has been paid to the causes and mechanisms contributing to NAFLD development in normal-weight individuals. One of the main causes of NAFLD in normal-weight individuals is the accumulation of visceral and muscular fat and its interaction with the liver. Myosteatosis (triglyceride accumulation in the muscle) induces a loss of muscle by reducing blood flow and insulin diffusion, contributing to NAFLD. Normal-weight patients with NAFLD exhibit higher serum markers of liver damage and C-reactive protein levels, as well as more pronounced insulin resistance, compared to healthy controls. Notably, increased levels of C-reactive protein and insulin resistance are strongly correlated with the risk of developing NAFLD/NASH. Gut dysbiosis has also been associated with NAFLD/NASH progression in normal-weight individuals. More investigation is required to elucidate the mechanisms leading to NAFLD in normal-weight individuals.
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Affiliation(s)
- Pablo Muriel
- Laboratory of Experimental Hepatology, Department of Pharmacology, Cinvestav-IPN, Mexico City
| | - Irina Cardoso-Lezama
- Laboratory of Experimental Hepatology, Department of Pharmacology, Cinvestav-IPN, Mexico City
| | - Eduardo E Vargas-Pozada
- Laboratory of Experimental Hepatology, Department of Pharmacology, Cinvestav-IPN, Mexico City
| | - Erika Ramos-Tovar
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Casco de Santo Tomás, Ciudad de México, Mexico
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26
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Grapentine S, Singh RK, Bakovic M. Skeletal Muscle Consequences of Phosphatidylethanolamine Synthesis Deficiency. FUNCTION 2023; 4:zqad020. [PMID: 37342414 PMCID: PMC10278983 DOI: 10.1093/function/zqad020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 04/24/2023] [Accepted: 04/25/2023] [Indexed: 06/22/2023] Open
Abstract
The maintenance of phospholipid homeostasis is increasingly being implicated in metabolic health. Phosphatidylethanolamine (PE) is the most abundant phospholipid on the inner leaflet of cellular membranes, and we have previously shown that mice with a heterozygous ablation of the PE synthesizing enzyme, Pcyt2 (Pcyt2+/-), develop obesity, insulin resistance, and NASH. Skeletal muscle is a major determinant of systemic energy metabolism, making it a key player in metabolic disease development. Both the total PE levels and the ratio of PE to other membrane lipids in skeletal muscle are implicated in insulin resistance; however, the underlying mechanisms and the role of Pcyt2 regulation in this association remain unclear. Here, we show how reduced phospholipid synthesis due to Pcyt2 deficiency causes Pcyt2+/- skeletal muscle dysfunction and metabolic abnormalities. Pcyt2+/- skeletal muscle exhibits damage and degeneration, with skeletal muscle cell vacuolization, disordered sarcomeres, mitochondria ultrastructure irregularities and paucity, inflammation, and fibrosis. There is intramuscular adipose tissue accumulation, and major disturbances in lipid metabolism with impaired FA mobilization and oxidation, elevated lipogenesis, and long-chain fatty acyl-CoA, diacylglycerol, and triacylglycerol accumulation. Pcyt2+/- skeletal muscle exhibits perturbed glucose metabolism with elevated glycogen content, impaired insulin signaling, and reduced glucose uptake. Together, this study lends insight into the critical role of PE homeostasis in skeletal muscle metabolism and health with broad implications on metabolic disease development.
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Affiliation(s)
- Sophie Grapentine
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph N1G 2W1, Canada
| | - Rathnesh K Singh
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph N1G 2W1, Canada
| | - Marica Bakovic
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph N1G 2W1, Canada
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27
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Liu CF, Chien LW. Predictive Role of Neutrophil-Percentage-to-Albumin Ratio (NPAR) in Nonalcoholic Fatty Liver Disease and Advanced Liver Fibrosis in Nondiabetic US Adults: Evidence from NHANES 2017-2018. Nutrients 2023; 15:nu15081892. [PMID: 37111111 PMCID: PMC10141547 DOI: 10.3390/nu15081892] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/31/2023] [Accepted: 04/11/2023] [Indexed: 04/29/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is highly prevalent globally and includes chronic liver diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). The neutrophil-to-albumin ratio (NPAR) is a cost-effective, readily available biomarker of inflammation used to assess cancer and cardiovascular disease prognosis, and it may be of predictive value in NAFLD. This study was to evaluate the associations between the NPAR, the neutrophil-to-lymphocyte ratio (NLR), and the presence of NAFLD or advanced liver fibrosis, and to assess the predictive value of the NPAR in NAFLD in a nationally representative database. This population-based, cross-sectional, retrospective study analyzed the secondary data of adults with NAFLD or advanced liver fibrosis extracted from the National Health and Nutrition Examination Survey (NHANES) database 2017-2018. NHANES participants with complete information of vibration-controlled transient elastography (VCTE) and controlled attenuation parameter (CAP) were enrolled. A logistic regression analysis was used to determine the associations between the variables in the participants with and without NAFLD or advanced liver fibrosis. The mean values of the lymphocyte counts, neutrophil counts, NPAR, aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), total cholesterol, triglycerides, and HbA1c were significantly higher in the participants with NAFLD than in those without NAFLD or advanced liver fibrosis. The mean blood albumin levels of the subjects without NAFLD or advancing fibrosis were considerably greater than those of the individuals with these conditions. The mean values of the NLR, NPAR, AST, ALT, triglycerides, lymphocyte count, neutrophil count, and HbA1c were significantly higher in patients with advanced fibrosis than in those without advanced fibrosis. A multivariate analysis showed that per unit increases in both the NLR and NPAR were significantly associated with an increased risk of developing NAFLD, while neither the NLR nor NPAR was significantly associated with higher odds of advanced fibrosis. In conclusion, the novel biomarker NPAR demonstrates a good association with NAFLD, along with participants' clinical characteristics, in a nationwide population. The NPAR may serve as a biomarker for NAFLD and help clinicians refine the diagnosis and treatment of chronic liver disease.
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Affiliation(s)
- Chi-Feng Liu
- School of Nursing, National Taipei University of Nursing and Health Science, Taipei 112, Taiwan
| | - Li-Wei Chien
- Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 112, Taiwan
- Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei 112, Taiwan
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Dumond Bourie A, Potier JB, Pinget M, Bouzakri K. Myokines: Crosstalk and Consequences on Liver Physiopathology. Nutrients 2023; 15:nu15071729. [PMID: 37049569 PMCID: PMC10096786 DOI: 10.3390/nu15071729] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 03/29/2023] [Accepted: 03/30/2023] [Indexed: 04/03/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease mainly characterized by the hepatic accumulation of lipid inducing a deregulation of β-oxidation. Its advanced form is non-alcoholic steatohepatitis (NASH), which, in addition to lipid accumulation, induces hepatocellular damage, oxidative stress and fibrosis that can progress to cirrhosis and to its final stage: hepatocellular carcinoma (HCC). To date, no specific therapeutic treatment exists. The implications of organ crosstalk have been highlighted in many metabolic disorders, such as diabetes, metabolic-associated liver diseases and obesity. Skeletal muscle, in addition to its role as a reservoir and consumer of energy and carbohydrate metabolism, is involved in this inter-organs’ communication through different secreted products: myokines, exosomes and enzymes, for example. Interestingly, resistance exercise has been shown to have a beneficial impact on different metabolic pathways, such as lipid oxidation in different organs through their secreted products. In this review, we will mainly focus on myokines and their effects on non-alcoholic fatty liver disease, and their complication: non-alcoholic steatohepatitis and HCC.
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Affiliation(s)
- Aurore Dumond Bourie
- European Center for the Study of Diabetes (CeeD), Research Unit of Strasbourg University “Diabetes and Therapeutics”, UR7294, 67200 Strasbourg, France
| | | | - Michel Pinget
- European Center for the Study of Diabetes (CeeD), Research Unit of Strasbourg University “Diabetes and Therapeutics”, UR7294, 67200 Strasbourg, France
| | - Karim Bouzakri
- European Center for the Study of Diabetes (CeeD), Research Unit of Strasbourg University “Diabetes and Therapeutics”, UR7294, 67200 Strasbourg, France
- ILONOV, 67200 Strasbourg, France
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van Laar A, Grootaert C, Rajkovic A, Desmet T, Beerens K, Van Camp J. Rare Sugar Metabolism and Impact on Insulin Sensitivity along the Gut-Liver-Muscle Axis In Vitro. Nutrients 2023; 15:1593. [PMID: 37049441 PMCID: PMC10096767 DOI: 10.3390/nu15071593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/21/2023] [Accepted: 03/22/2023] [Indexed: 03/29/2023] Open
Abstract
Rare sugars have recently attracted attention as potential sugar replacers. Understanding the biochemical and biological behavior of these sugars is of importance in (novel) food formulations and prevention of type 2 diabetes. In this study, we investigated whether rare sugars may positively affect intestinal and liver metabolism, as well as muscle insulin sensitivity, compared to conventional sugars. Rare disaccharide digestibility, hepatic metabolism of monosaccharides (respirometry) and the effects of sugars on skeletal muscle insulin sensitivity (impaired glucose uptake) were investigated in, respectively, Caco-2, HepG2 and L6 cells or a triple coculture model with these cells. Glucose and fructose, but not l-arabinose, acutely increased extracellular acidification rate (ECAR) responses in HepG2 cells and impaired glucose uptake in L6 cells following a 24 h exposure at 28 mM. Cellular bioenergetics and digestion experiments with Caco-2 cells indicate that especially trehalose (α1-1α), D-Glc-α1,2-D-Gal, D-Glc-α1,2-D-Rib and D-Glc-α1,3-L-Ara experience delayed digestion and reduced cellular impact compared to maltose (α1-4), without differences on insulin-stimulated glucose uptake in a short-term setup with a Caco-2/HepG2/L6 triple coculture. These results suggest a potential for l-arabinose and specific rare disaccharides to improve metabolic health; however, additional in vivo research with longer sugar exposures should confirm their beneficial impact on insulin sensitivity in humans.
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Affiliation(s)
- Amar van Laar
- NutriFOODChem, Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, 9000 Ghent, Belgium
| | - Charlotte Grootaert
- NutriFOODChem, Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, 9000 Ghent, Belgium
| | - Andreja Rajkovic
- NutriFOODChem, Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, 9000 Ghent, Belgium
- Food Microbiology and Food Preservation, Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, 9000 Ghent, Belgium
| | - Tom Desmet
- Centre for Synthetic Biology, Department of Biotechnology, Faculty of Bioscience Engineering, Ghent University, 9000 Ghent, Belgium
| | - Koen Beerens
- Centre for Synthetic Biology, Department of Biotechnology, Faculty of Bioscience Engineering, Ghent University, 9000 Ghent, Belgium
| | - John Van Camp
- NutriFOODChem, Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, 9000 Ghent, Belgium
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Roh E. Association of Myosteatosis with Nonalcoholic Fatty Liver Disease, Severity, and Liver Fibrosis Using Visual Muscular Quality Map in Computed Tomography (Diabetes Metab J 2023;47:104-17). Diabetes Metab J 2023; 47:301-303. [PMID: 36944453 PMCID: PMC10040619 DOI: 10.4093/dmj.2023.0051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/17/2023] Open
Affiliation(s)
- Eun Roh
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Corresponding author: Eun Roh https://orcid.org/0000-0001-8413-5006 Department of Internal Medicine, Hallym University College of Medicine, 1 Hallimdaehak-gil, Chuncheon 24252, Korea E-mail:
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Iwaki M, Kobayashi T, Nogami A, Saito S, Nakajima A, Yoneda M. Impact of Sarcopenia on Non-Alcoholic Fatty Liver Disease. Nutrients 2023; 15:nu15040891. [PMID: 36839249 PMCID: PMC9965462 DOI: 10.3390/nu15040891] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 02/07/2023] [Accepted: 02/08/2023] [Indexed: 02/12/2023] Open
Abstract
With the increasing incidence of non-alcoholic fatty liver disease (NAFLD) and the aging of the population, sarcopenia is attracting attention as one of the pathological conditions involved in the development and progression of NAFLD. In NAFLD, sarcopenia is closely associated with insulin resistance and results from the atrophy of skeletal muscle, an insulin target organ. In addition, inflammatory cytokines that promote skeletal muscle protein breakdown, low adiponectin levels leading to decreased insulin sensitivity, and hyperleptinemia are also involved in NAFLD pathogenesis. The presence of sarcopenia is a prognostic factor and increases the risk of mortality in patients with cirrhosis and post-treatment liver cancer. Sarcopenia, the presence of which mainly occurs due to decreased muscle mass, combined with increased visceral fat, can lead to sarcopenia-associated obesity, which increases the risk of NASH, liver fibrosis, and cardiovascular disease. In order to treat sarcopenia, it is necessary to properly evaluate sarcopenia status. Patients with high BMI, as in sarcopenic obesity, may improve with caloric restriction. However, inadequate oral intake may lead to further loss of muscle mass. Aerobic and resistance exercise should also be used appropriately.
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Targher G, Mantovani A, Byrne CD. Mechanisms and possible hepatoprotective effects of glucagon-like peptide-1 receptor agonists and other incretin receptor agonists in non-alcoholic fatty liver disease. Lancet Gastroenterol Hepatol 2023; 8:179-191. [PMID: 36620987 DOI: 10.1016/s2468-1253(22)00338-7] [Citation(s) in RCA: 56] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 09/22/2022] [Accepted: 09/29/2022] [Indexed: 01/07/2023]
Abstract
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretins that stimulate insulin secretion from pancreatic β cells in response to food ingestion. Modified GLP-1 and GIP peptides are potent agonists for their incretin receptors, and some evidence shows that the dual GLP-1 and GIP receptor agonist tirzepatide is effective in promoting marked weight loss. GLP-1 receptor agonists signal in the CNS to suppress appetite, increase satiety, and thereby decrease calorie intake, but many other effects of incretin signalling have been recognised that are relevant to the treatment of non-alcoholic fatty liver disease (NAFLD). This Review provides an overview of the literature supporting the notion that endogenous incretins and incretin-receptor agonist treatments are important not only for decreasing risk of developing NAFLD, but also for treating NAFLD and NAFLD-related complications. We discuss incretin signalling and related incretin-receptor agonist treatments, mechanisms in key relevant tissues affecting liver disease, and clinical data from randomised controlled trials. Finally, we present future perspectives in this rapidly developing field of research and clinical medicine.
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Affiliation(s)
- Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, UK; Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK
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Prokopidis K, Witard OC. Understanding the role of smoking and chronic excess alcohol consumption on reduced caloric intake and the development of sarcopenia. Nutr Res Rev 2022; 35:197-206. [PMID: 34027849 DOI: 10.1017/s0954422421000135] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This narrative review provides mechanistic insight into the biological link between smoking and/or chronic excess alcohol consumption, and increased risk of developing sarcopenia. Although the combination of excessive alcohol consumption and smoking is often associated with ectopic adipose deposition, this review is focused on the context of a reduced caloric intake (leading to energy deficit) that also may ensue due to either lifestyle habit. Smoking is a primary cause of periodontitis and chronic obstructive pulmonary disease that both induce swallowing difficulties, inhibit taste and mastication, and are associated with increased risk of muscle atrophy and mitochondrial dysfunction. Smoking may contribute to physical inactivity, energy deficit via reduced caloric intake, and increased systemic inflammation, all of which are factors known to suppress muscle protein synthesis rates. Moreover, chronic excess alcohol consumption may result in gut microbiota dysbiosis and autophagy-induced hyperammonemia, initiating the up-regulation of muscle protein breakdown and down-regulation of muscle protein synthesis via activation of myostatin, AMPK and REDD1, and deactivation of IGF-1. Future research is warranted to explore the link between oral healthcare management and personalised nutrition counselling in light of potential detrimental consequences of chronic smoking on musculoskeletal health outcomes in older adults. Experimental studies should investigate the impact of smoking and chronic excess alcohol consumption on the gut-brain axis, and explore biomarkers of smoking-induced oral disease progression. The implementation of behavioural change interventions and health policies regarding smoking and alcohol intake habits may mitigate the clinical and financial burden of sarcopenia on the healthcare system.
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Affiliation(s)
- Konstantinos Prokopidis
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, White City, London, UK
| | - Oliver C Witard
- Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
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Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Clinical and Research Implications. Int J Mol Sci 2022; 23:ijms232113320. [PMID: 36362108 PMCID: PMC9654863 DOI: 10.3390/ijms232113320] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 10/25/2022] [Accepted: 10/28/2022] [Indexed: 11/06/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide, affecting up to ~30% of adult populations. NAFLD defines a spectrum of progressive liver conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma, which often occur in close and bidirectional associations with metabolic disorders. Chronic kidney disease (CKD) is characterized by anatomic and/or functional renal damage, ultimately resulting in a reduced glomerular filtration rate. The physiological axis linking the liver and kidneys often passes unnoticed until clinically significant portal hypertension, as a major complication of cirrhosis, becomes apparent in the form of ascites, refractory ascites, or hepatorenal syndrome. However, the extensive evidence accumulated since 2008 indicates that noncirrhotic NAFLD is associated with a higher risk of incident CKD, independent of obesity, type 2 diabetes, and other common renal risk factors. In addition, subclinical portal hypertension has been demonstrated to occur in noncirrhotic NAFLD, with a potential adverse impact on renal vasoregulation. However, the mechanisms underlying this association remain unexplored to a substantial extent. With this background, in this review we discuss the current evidence showing a strong association between NAFLD and the risk of CKD, and the putative biological mechanisms underpinning this association. We also discuss in depth the potential pathogenic role of the hepatorenal reflex, which may be triggered by subclinical portal hypertension and is a poorly investigated but promising research topic. Finally, we address emerging pharmacotherapies for NAFLD that may also beneficially affect the risk of developing CKD in individuals with NAFLD.
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Non-alcoholic fatty liver disease-related fibrosis and sarcopenia: An altered liver-muscle crosstalk leading to increased mortality risk. Ageing Res Rev 2022; 80:101696. [PMID: 35843589 DOI: 10.1016/j.arr.2022.101696] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 06/11/2022] [Accepted: 07/13/2022] [Indexed: 11/22/2022]
Abstract
In the last few decades, the loss of skeletal muscle mass and function, known as sarcopenia, has significantly increased in prevalence, becoming a major global public health concern. On the other hand, the prevalence of non-alcoholic fatty liver disease (NAFLD) has also reached pandemic proportions, constituting the leading cause of hepatic fibrosis worldwide. Remarkably, while sarcopenia and NAFLD-related fibrosis are independently associated with all-cause mortality, the combination of both conditions entails a greater risk for all-cause and cardiac-specific mortality. Interestingly, both sarcopenia and NAFLD-related fibrosis share common pathophysiological pathways, including insulin resistance, chronic inflammation, hyperammonemia, alterations in the regulation of myokines, sex hormones and growth hormone/insulin-like growth factor-1 signaling, which may explain reciprocal connections between these two disorders. Additional contributing factors, such as the gut microbiome, may also play a role in this relationship. In skeletal muscle, phosphatidylinositol 3-kinase/Akt and myostatin signaling are the central anabolic and catabolic pathways, respectively, and the imbalance between them can lead to muscle wasting in patients with NAFLD-related fibrosis. In this review, we summarize the bidirectional influence between NAFLD-related fibrosis and sarcopenia, highlighting the main potential mechanisms involved in this complex crosstalk, and we discuss the synergistic effects of both conditions in overall and cardiovascular mortality.
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Jin R, Wang X, Li X, Yang J, Liu B, Wei L, Liu F, Rao H. Appendicular Skeletal Muscle Index and HbA1c Evaluate Liver Steatosis in Patients With Metabolic Associated Fatty Liver Disease. Front Med (Lausanne) 2022; 9:919502. [PMID: 35872790 PMCID: PMC9298827 DOI: 10.3389/fmed.2022.919502] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 06/20/2022] [Indexed: 11/21/2022] Open
Abstract
Background and Aim(s) Liver steatosis, as the main feature of metabolic associated fatty liver disease (MAFLD), was associated with the progression of liver fibrosis and metabolic syndrome, which needed to be estimated accurately. In this study, we explored the significance of appendicular skeletal muscle index (ASMI) in evaluating liver steatosis of MAFLD patients. Methods Eight hundred and ninety-nine cases with MAFLD from 2017 to 2018 National Health and Nutrition Examination Surveys (NHANES) database were included. All the analyzed data were obtained from NHANES database. The association between ASMI and liver steatosis were evaluated using R and EmpowerStats. Results MAFLD individuals were randomly divided into a training (n = 450) and validation cohort (n = 449). In univariate analysis, HbA1c, arms fat, arms lean mass, legs lean mass, trunk lean mass, total fat, total lean mass and ASMI were significantly associated with liver steatosis (p < 0.05). Multivariate analysis showed that HbA1c (OR: 1.6732; 95% CI: 1.2753–2.1929, p = 0.0002) and ASMI (OR: 1.6723; 95% CI: 1.1760–2.5204, p = 0.0052) were independently associated with severe liver steatosis. ASMI accurately evaluated severe liver steatosis with an AUROC of 0.73 and 0.81 in training and validation cohort, respectively. Compared with ASMI only, ASMI combined with HbA1c improved the AUROC to 0.85 and 0.88. Furthermore, the AUROC of our model was superior to FLI in the evaluation of liver steatosis. Conclusion ASMI combined with HbA1c has good evaluation value for liver steatosis in MAFLD patients, which might be beneficial for the management of MAFLD clinically.
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Affiliation(s)
- Rui Jin
- Peking University People’s Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
| | - Xiaoxiao Wang
- Peking University People’s Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
| | - Xiaohe Li
- Peking University People’s Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
| | - Jia Yang
- Peking University People’s Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
| | - Baiyi Liu
- Peking University People’s Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
| | - Lai Wei
- Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Feng Liu
- Peking University People’s Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
- *Correspondence: Feng Liu,
| | - Huiying Rao
- Peking University People’s Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China
- Huiying Rao,
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Choe EK, Shivakumar M, Verma A, Verma SS, Choi SH, Kim JS, Kim D. Leveraging deep phenotyping from health check-up cohort with 10,000 Korean individuals for phenome-wide association study of 136 traits. Sci Rep 2022; 12:1930. [PMID: 35121771 PMCID: PMC8817039 DOI: 10.1038/s41598-021-04580-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 12/17/2021] [Indexed: 11/09/2022] Open
Abstract
The expanding use of the phenome-wide association study (PheWAS) faces challenges in the context of using International Classification of Diseases billing codes for phenotype definition, imbalanced study population ethnicity, and constrained application of the results in research. We performed a PheWAS utilizing 136 deep phenotypes corroborated by comprehensive health check-ups in a Korean population, along with trans-ethnic comparisons through using the UK Biobank and Biobank Japan Project. Meta-analysis with Korean and Japanese population was done. The PheWAS associated 65 phenotypes with 14,101 significant variants (P < 4.92 × 10-10). Network analysis, visualization of cross-phenotype mapping, and causal inference mapping with Mendelian randomization were conducted. Among phenotype pairs from the genotype-driven cross-phenotype associations, we evaluated penetrance in correlation analysis using a clinical database. We focused on the application of PheWAS in order to make it robust and to aid the derivation of biological meaning post-PheWAS. This comprehensive analysis of PheWAS results based on a health check-up database will provide researchers and clinicians with a panoramic overview of the networks among multiple phenotypes and genetic variants, laying groundwork for the practical application of precision medicine.
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Affiliation(s)
- Eun Kyung Choe
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, B304 Richards Building, 3700 Hamilton Walk, Philadelphia, PA, 19104-6116, USA.,Department of Surgery, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, 06236, South Korea
| | - Manu Shivakumar
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, B304 Richards Building, 3700 Hamilton Walk, Philadelphia, PA, 19104-6116, USA
| | - Anurag Verma
- Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Shefali Setia Verma
- Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Seung Ho Choi
- Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, 06236, South Korea
| | - Joo Sung Kim
- Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, 06236, South Korea. .,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, 03080, South Korea.
| | - Dokyoon Kim
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, B304 Richards Building, 3700 Hamilton Walk, Philadelphia, PA, 19104-6116, USA. .,Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, 19104, USA.
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Zambon Azevedo V, Silaghi CA, Maurel T, Silaghi H, Ratziu V, Pais R. Impact of Sarcopenia on the Severity of the Liver Damage in Patients With Non-alcoholic Fatty Liver Disease. Front Nutr 2022; 8:774030. [PMID: 35111794 PMCID: PMC8802760 DOI: 10.3389/fnut.2021.774030] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 12/21/2021] [Indexed: 12/12/2022] Open
Abstract
An extensive body of the literature shows a strong interrelationship between the pathogenic pathways of non-alcoholic fatty liver disease (NAFLD) and sarcopenia through the muscle-liver-adipose tissue axis. NAFLD is one of the leading causes of chronic liver diseases (CLD) affecting more than one-quarter of the general population worldwide. The disease severity spectrum ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis, and its complications: end-stage chronic liver disease and hepatocellular carcinoma. Sarcopenia, defined as a progressive loss of the skeletal muscle mass, reduces physical performances, is associated with metabolic dysfunction and, possibly, has a causative role in NAFLD pathogenesis. Muscle mass is a key determinant of the whole-body insulin-mediated glucose metabolism and impacts fatty liver oxidation and energy homeostasis. These mechanisms drive the accumulation of ectopic fat both in the liver (steatosis, fatty liver) and in the muscle (myosteatosis). Myosteatosis rather than the muscle mass per se, seems to be closely associated with the severity of the liver injury. Sarcopenic obesity is a recently described entity which associates both sarcopenia and obesity and may trigger worse clinical outcomes including hepatic fibrosis progression and musculoskeletal disabilities. Furthermore, the muscle-liver-adipose tissue axis has a pivotal role in changes of the body composition, resulting in a distinct clinical phenotype that enables the identification of the "sarcopenic NAFLD phenotype." This review aims to bring some light into the complex relationship between sarcopenia and NAFLD and critically discuss the key mechanisms linking NAFLD to sarcopenia, as well as some of the clinical consequences associated with the coexistence of these two entities: the impact of body composition phenotypes on muscle morphology, the concept of sarcopenic obesity, the relationship between sarcopenia and the severity of the liver damage and finally, the future directions and the existing gaps in the knowledge.
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Affiliation(s)
- Vittoria Zambon Azevedo
- Doctoral School Physiology, Physiopathology and Therapeutics 394, Sorbonne Université, Paris, France
- Centre de Recherche de Cordeliers, INSERM UMRS 1138, Paris, France
| | - Cristina Alina Silaghi
- Department of Endocrinology, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
| | - Thomas Maurel
- Institute of Cardiometabolism and Nutrition, Paris, France
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France
| | - Horatiu Silaghi
- Department of Surgery V, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
| | - Vlad Ratziu
- Centre de Recherche de Cordeliers, INSERM UMRS 1138, Paris, France
- Institute of Cardiometabolism and Nutrition, Paris, France
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France
- Sorbonne Université, Paris, France
| | - Raluca Pais
- Institute of Cardiometabolism and Nutrition, Paris, France
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France
- Sorbonne Université, Paris, France
- Centre de Recherche Saint Antoine, INSERM UMRS 938, Paris, France
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Lee HJ, Chang JS, Ahn JH, Kim MY, Park KS, Ahn YS, Koh SB. Association Between Low Muscle Mass and Non-alcoholic Fatty Liver Disease Diagnosed Using Ultrasonography, Magnetic Resonance Imaging Derived Proton Density Fat Fraction, and Comprehensive NAFLD Score in Korea. J Prev Med Public Health 2021; 54:412-421. [PMID: 34875824 PMCID: PMC8655369 DOI: 10.3961/jpmph.21.387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Accepted: 09/15/2021] [Indexed: 11/24/2022] Open
Abstract
Objectives Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent metabolic disease. Muscle is known to influence NAFLD development. Therefore, this study aimed to determine the relationships among low muscle mass, NAFLD, and hepatic fibrosis using various definitions of low muscle mass and NAFLD diagnostic methods, including magnetic resonance imaging-based proton density fat fraction (MRI-PDFF). Methods This cross-sectional study included 320 participants (107 males, 213 females) from the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population cohort. Muscle mass was assessed using whole-body dual-energy X-ray absorptiometry and adjusted for the height squared, body weight, and body mass index (BMI). NAFLD was diagnosed using ultrasonography (US), MRI-PDFF, and the comprehensive NAFLD score (CNS). Hepatic fibrosis was assessed using magnetic resonance elastography. Multivariable logistic and linear regression analyses were performed to determine the aforementioned associations. Results According to US, 183 participants (57.2%) had NAFLD. Muscle mass adjusted for body weight was associated with NAFLD diagnosed using US (odds ratio [OR], 3.00; 95% confidence interval [CI], 1.70 to 5.31), MRI-PDFF (OR, 2.00; 95% CI, 1.13 to 3.53), and CNS (OR, 3.39; 95% CI, 1.73 to 6.65) and hepatic fibrosis (males: β=-0.070, p<0.01; females: β=-0.037, p<0.04). Muscle mass adjusted for BMI was associated with NAFLD diagnosed by US (OR, 1.71; 95% CI, 1.02 to 2.86) and CNS (OR, 1.95; 95% CI, 1.04 to 3.65), whereas muscle mass adjusted for height was not associated with NAFLD. Conclusions Low muscle mass was associated with NAFLD and liver fibrosis; therefore, maintaining sufficient muscle mass is important to prevent NAFLD. A prospective study and additional consideration of muscle quality are needed to strengthen the findings regarding this association.
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Affiliation(s)
- Hun Ju Lee
- Department of Preventive Medicine, Yonsei Wonju University College of Medicine, Wonju, Korea
| | - Jae Seung Chang
- Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Jhii Hyun Ahn
- Department of Radiology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Kyu-Sang Park
- Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Yeon-Soon Ahn
- Department of Preventive Medicine, Yonsei Wonju University College of Medicine, Wonju, Korea
| | - Sang Baek Koh
- Department of Preventive Medicine, Yonsei Wonju University College of Medicine, Wonju, Korea
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Kim HK, Kim CH. Quality Matters as Much as Quantity of Skeletal Muscle: Clinical Implications of Myosteatosis in Cardiometabolic Health. Endocrinol Metab (Seoul) 2021; 36:1161-1174. [PMID: 34986299 PMCID: PMC8743592 DOI: 10.3803/enm.2021.1348] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 12/13/2021] [Indexed: 12/12/2022] Open
Abstract
Although age-related changes in skeletal muscles are closely associated with decreases in muscle strength and functional decline, their associations with cardiometabolic diseases in the literature are inconsistent. Such inconsistency could be explained by the fact that muscle quality-which is closely associated with fatty infiltration of the muscle (i.e., myosteatosis)-is as important as muscle quantity in cardiometabolic health. However, muscle quality has been less explored compared with muscle mass. Moreover, the standard definition of myosteatosis and its assessment methods have not been established yet. Recently, some techniques using single axial computed tomography (CT) images have been introduced and utilized in many studies, as the mass and quality of abdominal muscles could be measured opportunistically on abdominal CT scans obtained during routine clinical care. Yet, the mechanisms by which myosteatosis affect metabolic and cardiovascular health remain largely unknown. In this review, we explore the recent advances in the assessment of myosteatosis and its changes associated with aging. We also review the recent literature on the clinical implication of myosteatosis by focusing on metabolic and cardiovascular diseases. Finally, we discuss the challenges and unanswered questions that need addressing to set myosteatosis as a therapeutic target for the prevention or treatment of cardiometabolic diseases.
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Affiliation(s)
- Hong-Kyu Kim
- Subdivision of Endocrinology and Metabolism, Health Screening and Promotion Center, Asan Medical Center, Seoul, Korea
- Corresponding authors: Hong-Kyu Kim Subdivision of Endocrinology and Metabolism, Health Screening and Promotion Center, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea Tel: +82-2-3010-4802, Fax: +82-2-3010-4917, E-mail:
| | - Chul-Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea
- Chul-Hee Kim Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, 170 Jomaru-ro, Wonmi-gu, Bucheon 14584, Korea Tel: +82-32-621-5155, Fax: +82-32-621-5018, E-mail:
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Albhaisi S, Sanyal AJ. Gene-Environmental Interactions as Metabolic Drivers of Nonalcoholic Steatohepatitis. Front Endocrinol (Lausanne) 2021; 12:665987. [PMID: 34040583 PMCID: PMC8142267 DOI: 10.3389/fendo.2021.665987] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 04/19/2021] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) has emerged as a leading cause of chronic liver disease worldwide in the past few decades as a consequence of the global obesity epidemic and is associated with significant morbidity and mortality. NAFLD is closely associated with components of the metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease, suggesting a plausible metabolic mechanistic basis. Metabolic inflexibility is considered a nidus for NAFLD pathogenesis, causing lipotoxicity, mitochondrial dysfunction and cellular stress leading to inflammation, apoptosis and fibrogenesis, thus mediating disease progression into nonalcoholic steatohepatitis (NASH) and ultimately cirrhosis. In this review, we describe they key metabolic drivers that contribute to development of NAFLD and NASH, and we explain how NASH is a metabolic disease. Understanding the metabolic basis of NASH is crucial for the prevention and treatment of this disease.
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Affiliation(s)
- Somaya Albhaisi
- Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, United States
| | - Arun J. Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, United States
- *Correspondence: Arun J. Sanyal,
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