The Effect of Aerobic-Resistance Exercise on Serum Level of Retinol-Bonded Protein 4, Abdominal Obesity, and Metabolic Markers in Postmenopausal Women with Non-Alcoholic Fatty Liver

Document Type : Research Paper

Authors

1 Department of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan, Iran

2 Department of Exercise Physiology, Faculty of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran

3 Internal Medicine Specialist (Internist) MD, Mahshahr, Iran

Abstract

Background and Purpose: Aging and postmenopausal hormonal changes cause changes in the function of certain physiological systems of the body, and expose women to the risk of non-alcoholic fatty liver disease (NAFLD) in a unique manner. The present study was conducted to investigate the effect of aerobic-resistance exercise on serum concentration of retinol-bonded protein 4 (RBP4), abdominal obesity, and metabolic markers in postmenopausal women with non-alcoholic fatty liver.
Methodology: Twenty-four 50-68 year-old sedentary postmenopausal women with fatty liver were randomly divided into exercise and control groups. Aerobic (at intensity of 50% to 75% of maximum heart rate) and resistance (at intensity of 50% to 75% of a maximum repetition) exercises were carried out over three sessions per week for ten weeks. The following indices were measured: liver fat by ultrasound, RBP4 by ELISA method, insulin resistance index (HOMA-IR), anthropometric indices, lipid profile, and liver enzymes. The data were analyzed using ANCOVA, paired t, Wilcoxon, Pearson and Spearman tests.
Results: Aerobic-resistance exercise significantly reduced RBP4 level, insulin resistance index, fasting blood glucose, Anthropometric characteristics, aspartate aminotransferase (AST), triglyceride (TG), LDL, and fatty liver in the exercise group compared to those in the control group (p < 0.05). Moreover, RBP4 had significant relationships with fatty liver, triglyceride, abdominal obesity, and body weight (p < 0.05). No significant change was observed in alanine aminotransferase (ALT), fasting insulin, and HDL (P>0.05).
Conclusion: Aerobic-resistance exercise can reduce RBP4 level and insulin resistance, and improve NAFLD in postmenopausal women by reducing abdominal obesity and lipid profile.

Keywords


##Bruno AD, Rodrigues MH, Alvares MCB, Nahas-Neto J, Nahas EAP. Non-alcoholic fatty liver disease and its associated risk factors in Brazilian postmenopausal women. Climacteric. 2014;17(4):465-71.##Zhou Z, Chen H, Ju H, Sun M. Circulating retinol binding protein 4 levels in nonalcoholic fatty liver disease: a systematic review and meta-analysis. Lipids in health and disease. 2017;16(1):180.##McCarthy EM, Rinella ME. The role of diet and nutrient composition in nonalcoholic Fatty liver disease. J Acad Nutr Diet. 2012;112(3):401-9.##Lee YM, Low HC, Lim LG, Dan YY, Aung MO, Cheng CL, et al. Intragastric balloon significantly improves nonalcoholic fatty liver disease activity score in obese patients with nonalcoholic steatohepatitis: a pilot study. Gastrointest Endosc. 2012;76(4):756-60.##Brady CW. Liver disease in menopause. World J Gastroenterol.2015;21(25):7613-20.##Cai H, Lu S, Chen Y, Das Mbbs Mrcog S, Niu Z, Zhuo G, et al. Serum retinol binding protein 4 and galectin-3 binding protein as novel markers for postmenopausal nonalcoholic fatty liver disease. Clin Biochem. 2018;56:95-101.##El Hadi H, Di Vincenzo A, Vettor R, Rossato M. Cardio-Metabolic Disorders in Non-Alcoholic Fatty Liver Disease. Int J Mol Sci. 2019;20(9):2215.##Chang X, Yan H, Bian H, Xia M, Zhang L, Gao J, et al. Serum retinol binding protein 4 is associated with visceral fat in human with nonalcoholic fatty liver disease without known diabetes: a cross-sectional study. Lipids Health Dis. 2015;14:28.##Suh J-B, Kim S, Cho G-J, Choi K-M, Han J-H, Geun H. Elevated serum retinol-binding protein 4 is associated with insulin resistance in older women. Metabolism: clinical and experimental. 2009;59:118-22.##Klöting N, Graham TE, Berndt J, Kralisch S, Kovacs P, Wason CJ, et al. Serum Retinol-Binding Protein Is More Highly Expressed in Visceral than in Subcutaneous Adipose Tissue and Is a Marker of Intra-abdominal Fat Mass. Cell Metabolism. 2007;6(1):79-87.##Majerczyk M, Olszanecka-Glinianowicz M, Puzianowska-Kuźnicka M, Chudek J. Retinol-binding protein 4 (RBP4) as the causative factor and marker of vascular injury related to insulin resistance. Postepy Hig Med Dosw (Online). 2016;70(0):1267-75.##Majerczyk M, Kocełak P, Choręza P, Arabzada H, Owczarek AJ, Bożentowicz-Wikarek M, et al. Components of metabolic syndrome in relation to plasma levels of retinol binding protein 4 (RBP4) in a cohort of people aged 65 years and older. Journal of endocrinological investigation. 2018;41(10):1211-9.##Mansouri M, Nikooie R, Keshtkar A, Larijani B, Omidfar K. Effect of endurance training on retinol-binding protein 4 gene expression and its protein level in adipose tissue and the liver in diabetic rats induced by a high-fat diet and streptozotocin. J Diabetes Investig. 2014;5(5):484-91.##Bakshi S, Schmidt H, Baskin E, Croniger C, Thompson C, Bonfield T, et al. Sexual Dimorphism in Developmental and Diet Dependent Circulating Retinol Binding Protein 4. Obesity Science & Practice. 2018;4.##Seo JA, Kim NH, Park SY, Kim HY, Ryu OH, Lee KW, et al. Serum retinol-binding protein 4 levels are elevated in non-alcoholic fatty liver disease. Clin endocrinol. 2008;68(4):555-60.##Schina M, Koskinas J, Tiniakos D, Hadziyannis E, Savvas S, Karamanos B, et al. Circulating and liver tissue levels of retinol-binding protein-4 in non-alcoholic fatty liver disease. Hepatology research : the official journal of the Japan Society of Hepatology. 2009;39(10):972-8.##Graham TE, Yang Q, Blüher M, Hammarstedt A, Ciaraldi TP, Henry RR, et al. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Engl J Med. 2006;354(24):2552-63.##Ku YH, Han KA, Ahn H, Kwon H, Koo BK, Kim HC, et al. Resistance exercise did not alter intramuscular adipose tissue but reduced retinol-binding protein-4 concentration in individuals with type 2 diabetes mellitus. J Int Med Res. 2010;38(3):782-91.##Taghian F, Zolfaghari M, Hedayati M. Effects of Aerobic Exercise on Serum Retinol Binding Protein4, Insulin Resistance and Blood Lipids in Obese Women. Iran J Public Health. 2014;43(5):658–65.##Lamiquiz-Moneo I, Bea AM, Palacios-Pérez C, Miguel-Etayo PD, González-Gil EM, López-Ariño C, et al. Effect of Lifestyle Intervention in the Concentration of Adipoquines and Branched Chain Amino Acids in Subjects with High Risk of Developing Type 2 Diabetes: Feel4Diabetes Study. Cells. 2020;9(3):693.##Xia M, Liu Y, Guo H, Wang D, Wang Y, Ling W. Retinol binding protein 4 stimulates hepatic sterol regulatory element-binding protein 1 and increases lipogenesis through the peroxisome proliferator-activated receptor-γ coactivator 1β-dependent pathway. Hepatology. 2013;58(2):564-75.##Mansouri M, Keshtkar A, Hasani-Ranjbar S, Far E, Tabatabaei O, Omidfar K, et al. The impact of one session resistance exercise on plasma adiponectin and RBP4 concentration in trained and untrained healthy young men. Endocrine journal. 2011;58:861-8.##Stefan N, Hennige AM, Staiger H, Machann J, Schick F, Schleicher E, et al. High circulating retinol-binding protein 4 is associated with elevated liver fat but not with total, subcutaneous, visceral, or intramyocellular fat in humans. Diabetes Care. 2007;30(5):1173-8.##Kwak MS, Kim D. Non-alcoholic fatty liver disease and lifestyle modifications, focusing on physical activity. Korean J Intern Med. 2018;33(1):64-74.##Shamsoddini A, Sobhani V, Ghamar Chehreh ME, Alavian SM, Zaree A. Effect of Aerobic and Resistance Exercise Training on Liver Enzymes and Hepatic Fat in Iranian Men With Nonalcoholic Fatty Liver Disease. Hepatitis monthly. 2015;15(10):e31434-e.##Ispasoiu CA, Chicea R, Stamatian FV, Ispasoiu F. High Fasting Insulin Levels and Insulin Resistance May Be Linked to Idiopathic Recurrent Pregnancy Loss: A Case-Control Study. International Journal of Endocrinology. 2013;2013:576926.##Golding LA. Ymca  Fitness Testing and Assessment Manual. fourth ed: Human Kinetics; 2000.##Brzycki M. Strength Testing: Predicting a One-Rep Max from Reps to Fatigue. J Phys Educ Rec and Dance 1993;64(1):88–90.##Williams N. The Borg rating of perceived exertion (RPE) scale. Occup Med. 2017;67(5):404-5.##Jung C-H, Rhee E-J, Kwon H, Chang Y, Ryu S, Lee WY. Visceral-to-Subcutaneous Abdominal Fat Ratio Is Associated with Nonalcoholic Fatty Liver Disease and Liver Fibrosis. Endocrinology and Metabolism. 2020;35:165.##Chen X, Shen T, Li Q, Chen X, Li Y, Li D, et al. Retinol Binding Protein-4 Levels and Non-alcoholic Fatty Liver Disease: A community-based cross-sectional study. Scientific Reports. 2017;7:45100.##Haider DG, Schindler K, Prager G, Bohdjalian A, Luger A, Wolzt M, et al. Serum retinol-binding protein 4 is reduced after weight loss in morbidly obese subjects. J Clin Endocrinol Metab. 2007;92(3):1168-71.##Younesian A, Moradi H, Razavianzade N, Zahedi E. Prevalence of fatty liver using ultrasound in male high-school pupils without history of liver disease and its relationship with liver enzymes, body mass index and waist - hip ratio. RJMS. 2015;22(132):79-86. Persian.##Ahmadi N, Moghadasi M, Nuri R. Changes of serum retinol binding protein 4 levels following 8 weeks moderate aerobic exercise. Asian J Sports Med. 2013;4(3):208-12. Persian##Choi KM, Kim TN, Yoo HJ, Lee KW, Cho GJ, Hwang TG, et al. Effect of exercise training on A-FABP, lipocalin-2 and RBP4 levels in obese women. Clin Endocrinol (Oxf). 2009;70(4):569-74.##Hashida R, Kawaguchi T, Bekki M, Omoto M, Matsuse H, Nago T, et al. Aerobic vs. resistance exercise in non-alcoholic fatty liver disease: A systematic review. J Hepatol. 2017;66:142-52.##Jalali Z, Shabani R, Nazari M. Effects of concurrent resistance-endurance training on body composition, lipid profile and blood glucose homeostasis in obese girls: A clinical trial. Iranian Journal of Pediatric Nursing. 2018;4(4):24-34. Persian##Chung GE, Yim JY, Kim D, Lim SH, Yang JI, Kim YS, et al. The influence of metabolic factors for nonalcoholic Fatty liver disease in women. Biomed Res Int. 2015;2015:131528.##Tilg H, Moschen AR. Insulin resistance, inflammation, and non-alcoholic fatty liver disease. Trends Endocrinol Metab. 2008;19(10):371-9.##Terra X, Auguet T, Broch M, Sabench F, Hernández M, Pastor RM, et al. Retinol binding protein-4 circulating levels were higher in nonalcoholic fatty liver disease vs. histologically normal liver from morbidly obese women. Obesity (Silver Spring). 2013;21(1):170-7.##O'Leary VB, Marchetti CM, Krishnan RK, Stetzer BP, Gonzalez F, Kirwan JP. Exercise-induced reversal of insulin resistance in obese elderly is associated with reduced visceral fat. J Appl Physiol (1985). 2006;100(5):1584-9.##Moosavi-Sohroforouzani A, Ganbarzadeh M. Reviewing the physiological effects of aerobic and resistance training on insulin resistance and some biomarkers in non-alcoholic fatty liver disease. Feyz Journal of Kashan University of Medical Sciences. 2016;20(3):282-96. Persian##Zheng F, Cai Y. Concurrent exercise improves insulin resistance and nonalcoholic fatty liver disease by upregulating PPAR-γ and genes involved in the beta-oxidation of fatty acids in ApoE-KO mice fed a high-fat diet. Lipids in Health and Disease. 2019;18.##Lim S, Choi SH, Jeong IK, Kim JH, Moon MK, Park KS, et al. Insulin-sensitizing effects of exercise on adiponectin and retinol-binding protein-4 concentrations in young and middle-aged women. J Clin Endocrinol Metab. 2008;93(6):2263-8.##sheikholeslami-vatani d, Ebrahimi A. The Effect of Moderate-Intensity Continuous Training Vs. High-Intensity Interval Training on Visceral and Subcutaneous Fats in Obese Women. Journal of Rafsanjan University of Medical Sciences. 2018;16(11):999-1012. Persian##Alkhouri N, Lopez R, Berk M, Feldstein AE. Serum retinol-binding protein 4 levels in patients with nonalcoholic fatty liver disease. J Clin Gastroenterol. 2009;43(10):985-9.##Lewis J, Shand B, Elder P, Scott R. Plasma retinol-binding protein is unlikely to be a useful marker of insulin resistance. Diabetes research and clinical practice. 2008;80:e13-5.##Mehdizadeh R. The Effect of Core Stability Training on Body Composition and Lipoprotein in Menopausal Older Women. Salmand: Iranian Journal of Ageing. 2015;10(2):156-63. Persian##Hoseini kakhk S, Khaleghzadeh H, Nematy M, Hamedinia M. The Effect of Combined Aerobic-Resistance Training on Lipid Profile and Liver Enzymes in Patients with Nonalcoholic Fatty Liver Under Nutrition Diet. Sport physiology. 2015;27:65-84. Persian##Sarmadiyan M, Khorshidi D. Effect of combined training on body composition, lipids levels and indicators of metabolic syndrome in overweight and obesed postmenopausal women. Journal of Gerontology.2016;1(2):36-44. Persian##Takebayashi K, Aso Y, Inukai T. Role of retinol-binding protein 4 in the pathogenesis of Type 2 diabetes. Expert Rev Endocrinol  Metab. 2008;3(2):161-73.##Chen X, Shen T, Li Q, Chen X, Li Y, Li D, et al. Retinol Binding Protein-4 Levels and Non-alcoholic Fatty Liver Disease: A community-based cross-sectional study. Scientific Reports. 2017;7(1):45100.##Baek JH, Kim SJ, Kang HG, Lee HW, Kim JH, Hwang KA, et al. Galectin-3 activates PPARγ and supports white adipose tissue formation and high-fat diet-induced obesity. Endocrinology. 2015;156(1):147-56.##Broch M, Gómez JM, Auguet MT, Vilarrasa N, Pastor R, Elio I, et al. Association of retinol-binding protein-4 (RBP4) with lipid parameters in obese women. Obes Surg. 2010;20(9):12564-8.##Moradi Kelarde B, Azarbayjani M, Peeri M, Matin Homaee H. Effects of Nonlinear Resistance Training on Liver Biochemical Marker Levels in Postmenopausal Women with Nonalcoholic Fatty Liver Disease Scientific Journal of Rehabilition Medicine. 2017;5(4):136-45. Persian##Slentz CA, Bateman LA, Willis LH, Shields AT, Tanner CJ, Piner LW, et al. Effects of aerobic vs. resistance training on visceral and liver fat stores, liver enzymes, and insulin resistance by HOMA in overweight adults from STRRIDE AT/RT. Am J Physiol Endocrinol Metab. 2011;301(5):E1033-9.##Sookoian S, Pirola CJ. Liver enzymes, metabolomics and genome-wide association studies: from systems biology to the personalized medicine. World J Gastroenterol. 2015;21(3):711-25.##Sheng X, Che H, Ji Q, Yang F, Lv J, Wang Y, et al. The Relationship Between Liver Enzymes and Insulin Resistance in Type 2 Diabetes Patients with Nonalcoholic Fatty Liver Disease. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2018;50(5):397-402.##Skrypnik D, Ratajczak M, Karolkiewicz J, Mądry E, Pupek-Musialik D, Hansdorfer-Korzon R, et al. Effects of endurance and endurance-strength exercise on biochemical parameters of liver function in women with abdominal obesity. Biomed Pharmacother. 2016;80:1-7.##Devries MC, Samjoo IA, Hamadeh MJ, Tarnopolsky MA. Effect of endurance exercise on hepatic lipid content, enzymes, and adiposity in men and women. Obesity (Silver Spring). 2008;16(10):2281-8.##Rector R, Thyfault J, Morris R, Laye M, Borengasser S, Booth F, et al. Daily exercise increases hepatic fatty acid oxidation and prevents steatosis in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Am J Physiol Gastrointest Liver Physiol. 2008;294(3):G619–G26.##Yan H, Chang X, Xia M, Bian H, Zhang L, Lin H, et al. Serum retinol binding protein 4 is negatively related to beta cell function in Chinese women with non-alcoholic fatty liver disease: a cross-sectional study. Lipids Health Dis. 2013;12:157.##