Non-alcoholic fatty liver disease connections with fat-free tissues: A focus on bone and skeletal muscle

Eleonora Poggiogalle, Lorenzo Maria Donini, Andrea Lenzi, Claudio Chiesa, Lucia Pacifico, Eleonora Poggiogalle, Lorenzo Maria Donini, Andrea Lenzi, Claudio Chiesa, Lucia Pacifico

Abstract

The estimates of global incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) are worrisome, due to the parallel burden of obesity and its metabolic complications. Indeed, excess adiposity and insulin resistance represent two of the major risk factors for NAFLD; interestingly, in the last years a growing body of evidence tended to support a novel mechanistic perspective, in which the liver is at the center of a complex interplay involving organs and systems, other than adipose tissue and glucose homeostasis. Bone and the skeletal muscle are fat- free tissues which appeared to be independently associated with NAFLD in several cross-sectional studies. The deterioration of bone mineral density and lean body mass, leading to osteoporosis and sarcopenia, respectively, are age-related processes. The prevalence of NAFLD also increases with age. Beyond physiological aging, the three conditions share some common underlying mechanisms, and their elucidations could be of paramount importance to design more effective treatment strategies for the management of NAFLD. In this review, we provide an overview on epidemiological data as well as on potential contributors to the connections of NAFLD with bone and skeletal muscle.

Keywords: Bone; Non-alcoholic fatty liver disease; Osteoporosis; Sarcopenia; Skeletal muscle.

Conflict of interest statement

Conflict-of-interest statement: There are no potential conflicts of interest relevant to this article.

References

    1. Li L, Liu DW, Yan HY, Wang ZY, Zhao SH, Wang B. Obesity is an independent risk factor for non-alcoholic fatty liver disease: evidence from a meta-analysis of 21 cohort studies. Obes Rev. 2016;17:510–519.
    1. Dietrich P, Hellerbrand C. Non-alcoholic fatty liver disease, obesity and the metabolic syndrome. Best Pract Res Clin Gastroenterol. 2014;28:637–653.
    1. Fabbrini E, Sullivan S, Klein S. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology. 2010;51:679–689.
    1. Lonardo A, Bellentani S, Argo CK, Ballestri S, Byrne CD, Caldwell SH, Cortez-Pinto H, Grieco A, Machado MV, Miele L, et al. Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups. Dig Liver Dis. 2015;47:997–1006.
    1. Targher G, Lonardo A, Rossini M. Nonalcoholic fatty liver disease and decreased bone mineral density: is there a link? J Endocrinol Invest. 2015;38:817–825.
    1. Hong HC, Hwang SY, Choi HY, Yoo HJ, Seo JA, Kim SG, Kim NH, Baik SH, Choi DS, Choi KM. Relationship between sarcopenia and nonalcoholic fatty liver disease: the Korean Sarcopenic Obesity Study. Hepatology. 2014;59:1772–1778.
    1. Curtis E, Litwic A, Cooper C, Dennison E. Determinants of Muscle and Bone Aging. J Cell Physiol. 2015;230:2618–2625.
    1. Bertolotti M, Lonardo A, Mussi C, Baldelli E, Pellegrini E, Ballestri S, Romagnoli D, Loria P. Nonalcoholic fatty liver disease and aging: epidemiology to management. World J Gastroenterol. 2014;20:14185–14204.
    1. Hamaguchi M, Kojima T, Ohbora A, Takeda N, Fukui M, Kato T. Aging is a risk factor of nonalcoholic fatty liver disease in premenopausal women. World J Gastroenterol. 2012;18:237–243.
    1. Polyzos SA, Kountouras J, Tsatsoulis A, Zafeiriadou E, Katsiki E, Patsiaoura K, Zavos C, Anastasiadou VV, Slavakis A. Sex steroids and sex hormone-binding globulin in postmenopausal women with nonalcoholic fatty liver disease. Hormones (Athens) 2013;12:405–416.
    1. Xia MF, Lin HD, Yan HM, Bian H, Chang XX, Zhang LS, He WY, Gao X. The association of liver fat content and serum alanine aminotransferase with bone mineral density in middle-aged and elderly Chinese men and postmenopausal women. J Transl Med. 2016;14:11.
    1. Cui R, Sheng H, Rui XF, Cheng XY, Sheng CJ, Wang JY, Qu S. Low bone mineral density in chinese adults with nonalcoholic Fatty liver disease. Int J Endocrinol. 2013;2013:396545.
    1. Lee SH, Yun JM, Kim SH, Seo YG, Min H, Chung E, Bae YS, Ryou IS, Cho B. Association between bone mineral density and nonalcoholic fatty liver disease in Korean adults. J Endocrinol Invest. 2016;39:1329–1336.
    1. Moon SS, Lee YS, Kim SW. Association of nonalcoholic fatty liver disease with low bone mass in postmenopausal women. Endocrine. 2012;42:423–429.
    1. Purnak T, Beyazit Y, Ozaslan E, Efe C, Hayretci M. The evaluation of bone mineral density in patients with nonalcoholic fatty liver disease. Wien Klin Wochenschr. 2012;124:526–531.
    1. Bhatt SP, Nigam P, Misra A, Guleria R, Qadar Pasha MA. Independent associations of low 25 hydroxy vitamin D and high parathyroid hormonal levels with nonalcoholic fatty liver disease in Asian Indians residing in north India. Atherosclerosis. 2013;230:157–163.
    1. Yang HJ, Shim SG, Ma BO, Kwak JY. Association of nonalcoholic fatty liver disease with bone mineral density and serum osteocalcin levels in Korean men. Eur J Gastroenterol Hepatol. 2016;28:338–344.
    1. Pacifico L, Bezzi M, Lombardo CV, Romaggioli S, Ferraro F, Bascetta S, Chiesa C. Adipokines and C-reactive protein in relation to bone mineralization in pediatric nonalcoholic fatty liver disease. World J Gastroenterol. 2013;19:4007–4014.
    1. Pardee PE, Dunn W, Schwimmer JB. Non-alcoholic fatty liver disease is associated with low bone mineral density in obese children. Aliment Pharmacol Ther. 2012;35:248–254.
    1. Chang EJ, Yi DY, Yang HR. Vitamin D Status and Bone Mineral Density in Obese Children with Nonalcoholic Fatty Liver Disease. J Korean Med Sci. 2015;30:1821–1827.
    1. Pirgon O, Bilgin H, Tolu I, Odabas D. Correlation of insulin sensitivity with bone mineral status in obese adolescents with nonalcoholic fatty liver disease. Clin Endocrinol (Oxf) 2011;75:189–195.
    1. Henry CJ, Sedjo RL, Rozhok A, Salstrom J, Ahnen D, Levin TR, D’Agostino R, Haffner S, DeGregori J, Byers T. Lack of significant association between serum inflammatory cytokine profiles and the presence of colorectal adenoma. BMC Cancer. 2015;15:123.
    1. Strauss S, Gavish E, Gottlieb P, Katsnelson L. Interobserver and intraobserver variability in the sonographic assessment of fatty liver. AJR Am J Roentgenol. 2007;189:W320–W323.
    1. Sinclair M, Gow PJ, Grossmann M, Angus PW. Review article: sarcopenia in cirrhosis--aetiology, implications and potential therapeutic interventions. Aliment Pharmacol Ther. 2016;43:765–777.
    1. Koo BK, Kim D, Joo SK, Kim JH, Chang MS, Kim BG, Lee KL, Kim W. Sarcopenia is an independent risk factor for non-alcoholic steatohepatitis and significant fibrosis. J Hepatol. 2017;66:123–131.
    1. Lee YH, Jung KS, Kim SU, Yoon HJ, Yun YJ, Lee BW, Kang ES, Han KH, Lee HC, Cha BS. Sarcopaenia is associated with NAFLD independently of obesity and insulin resistance: Nationwide surveys (KNHANES 2008-2011) J Hepatol. 2015;63:486–493.
    1. Hashimoto Y, Osaka T, Fukuda T, Tanaka M, Yamazaki M, Fukui M. The relationship between hepatic steatosis and skeletal muscle mass index in men with type 2 diabetes. Endocr J. 2016;63:877–884.
    1. Moon JS, Yoon JS, Won KC, Lee HW. The role of skeletal muscle in development of nonalcoholic Fatty liver disease. Diabetes Metab J. 2013;37:278–285.
    1. Kim HY, Kim CW, Park CH, Choi JY, Han K, Merchant AT, Park YM. Low skeletal muscle mass is associated with non-alcoholic fatty liver disease in Korean adults: the Fifth Korea National Health and Nutrition Examination Survey. Hepatobiliary Pancreat Dis Int. 2016;15:39–47.
    1. Lee YH, Kim SU, Song K, Park JY, Kim do Y, Ahn SH, Lee BW, Kang ES, Cha BS, Han KH. Sarcopenia is associated with significant liver fibrosis independently of obesity and insulin resistance in nonalcoholic fatty liver disease: Nationwide surveys (KNHANES 2008-2011) Hepatology. 2016;63:776–786.
    1. Poggiogalle E, Lubrano C, Gnessi L, Mariani S, Lenzi A, Donini LM. Fatty Liver Index Associates with Relative Sarcopenia and GH/ IGF- 1 Status in Obese Subjects. PLoS One. 2016;11:e0145811.
    1. Dawson-Hughes B, Bischoff-Ferrari H. Considerations concerning the definition of sarcopenia: response to comments. Osteoporos Int. 2016;27:3147–3148.
    1. Tahimic CG, Wang Y, Bikle DD. Anabolic effects of IGF-1 signaling on the skeleton. Front Endocrinol (Lausanne) 2013;4:6.
    1. Perrini S, Laviola L, Carreira MC, Cignarelli A, Natalicchio A, Giorgino F. The GH/IGF1 axis and signaling pathways in the muscle and bone: mechanisms underlying age-related skeletal muscle wasting and osteoporosis. J Endocrinol. 2010;205:201–210.
    1. Bikle DD, Tahimic C, Chang W, Wang Y, Philippou A, Barton ER. Role of IGF-I signaling in muscle bone interactions. Bone. 2015;80:79–88.
    1. Loria P, Carulli L, Bertolotti M, Lonardo A. Endocrine and liver interaction: the role of endocrine pathways in NASH. Nat Rev Gastroenterol Hepatol. 2009;6:236–247.
    1. Takahashi Y. Essential roles of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in the liver. Endocr J. 2012;59:955–962.
    1. Aguirre GA, De Ita JR, de la Garza RG, Castilla-Cortazar I. Insulin-like growth factor-1 deficiency and metabolic syndrome. J Transl Med. 2016;14:3.
    1. Clemmons DR. The relative roles of growth hormone and IGF-1 in controlling insulin sensitivity. J Clin Invest. 2004;113:25–27.
    1. Ichikawa T, Nakao K, Hamasaki K, Furukawa R, Tsuruta S, Ueda Y, Taura N, Shibata H, Fujimoto M, Toriyama K, et al. Role of growth hormone, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 in development of non-alcoholic fatty liver disease. Hepatol Int. 2007;1:287–294.
    1. Sumida Y, Yonei Y, Tanaka S, Mori K, Kanemasa K, Imai S, Taketani H, Hara T, Seko Y, Ishiba H, et al. Lower levels of insulin-like growth factor-1 standard deviation score are associated with histological severity of non-alcoholic fatty liver disease. Hepatol Res. 2015;45:771–781.
    1. Völzke H, Nauck M, Rettig R, Dörr M, Higham C, Brabant G, Wallaschofski H. Association between hepatic steatosis and serum IGF1 and IGFBP-3 levels in a population-based sample. Eur J Endocrinol. 2009;161:705–713.
    1. Wang J, Zhou J, Bondy CA. Igf1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy. FASEB J. 1999;13:1985–1990.
    1. Wu S, Yang W, De Luca F. Insulin-Like Growth Factor-Independent Effects of Growth Hormone on Growth Plate Chondrogenesis and Longitudinal Bone Growth. Endocrinology. 2015;156:2541–2551.
    1. Matar M, Al-Shaar L, Maalouf J, Nabulsi M, Arabi A, Choucair M, Tamim H, El-Hajj Fuleihan G. The Relationship Between Calciotropic Hormones, IGF-1, and Bone Mass Across Pubertal Stages. J Clin Endocrinol Metab. 2016;101:4860–4870.
    1. Cianfarani S, Inzaghi E, Alisi A, Germani D, Puglianiello A, Nobili V. Insulin-like growth factor-I and -II levels are associated with the progression of nonalcoholic fatty liver disease in obese children. J Pediatr. 2014;165:92–98.
    1. Cabrera D, Ruiz A, Cabello-Verrugio C, Brandan E, Estrada L, Pizarro M, Solis N, Torres J, Barrera F, Arrese M. Diet-Induced Nonalcoholic Fatty Liver Disease Is Associated with Sarcopenia and Decreased Serum Insulin-Like Growth Factor-1. Dig Dis Sci. 2016;61:3190–3198.
    1. Wang X, Li W, Zhang Y, Yang Y, Qin G. Association between vitamin D and non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: results from a meta-analysis. Int J Clin Exp Med. 2015;8:17221–17234.
    1. Eliades M, Spyrou E, Agrawal N, Lazo M, Brancati FL, Potter JJ, Koteish AA, Clark JM, Guallar E, Hernaez R. Meta-analysis: vitamin D and non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2013;38:246–254.
    1. Kwok RM, Torres DM, Harrison SA. Vitamin D and nonalcoholic fatty liver disease (NAFLD): is it more than just an association? Hepatology. 2013;58:1166–1174.
    1. Foroughi M, Maghsoudi Z, Askari G. The effect of vitamin D supplementation on blood sugar and different indices of insulin resistance in patients with non-alcoholic fatty liver disease (NAFLD) Iran J Nurs Midwifery Res. 2016;21:100–104.
    1. Barchetta I, Del Ben M, Angelico F, Di Martino M, Fraioli A, La Torre G, Saulle R, Perri L, Morini S, Tiberti C, et al. No effects of oral vitamin D supplementation on non-alcoholic fatty liver disease in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. BMC Med. 2016;14:92.
    1. Abramovitch S, Sharvit E, Weisman Y, Bentov A, Brazowski E, Cohen G, Volovelsky O, Reif S. Vitamin D inhibits development of liver fibrosis in an animal model but cannot ameliorate established cirrhosis. Am J Physiol Gastrointest Liver Physiol. 2015;308:G112–G120.
    1. Anderson PH, Sawyer RK, Moore AJ, May BK, O’Loughlin PD, Morris HA. Vitamin D depletion induces RANKL-mediated osteoclastogenesis and bone loss in a rodent model. J Bone Miner Res. 2008;23:1789–1797.
    1. Reid IR, Bolland MJ, Grey A. Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis. Lancet. 2014;383:146–155.
    1. Kim MK, Baek KH, Song KH, Il Kang M, Park CY, Lee WY, Oh KW. Vitamin D deficiency is associated with sarcopenia in older Koreans, regardless of obesity: the Fourth Korea National Health and Nutrition Examination Surveys (KNHANES IV) 2009. J Clin Endocrinol Metab. 2011;96:3250–3256.
    1. Visser M, Deeg DJ, Lips P. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab. 2003;88:5766–5772.
    1. Ceglia L. Vitamin D and its role in skeletal muscle. Curr Opin Clin Nutr Metab Care. 2009;12:628–633.
    1. Singh S, Kumar D, Lal AK. Serum Osteocalcin as a Diagnostic Biomarker for Primary Osteoporosis in Women. J Clin Diagn Res. 2015;9:RC04–RC07.
    1. Vs K, K P, Ramesh M, Venkatesan V. The association of serum osteocalcin with the bone mineral density in post menopausal women. J Clin Diagn Res. 2013;7:814–816.
    1. Oldknow KJ, MacRae VE, Farquharson C. Endocrine role of bone: recent and emerging perspectives beyond osteocalcin. J Endocrinol. 2015;225:R1–R19.
    1. Wei J, Karsenty G. An overview of the metabolic functions of osteocalcin. Curr Osteoporos Rep. 2015;13:180–185.
    1. Yilmaz Y, Kurt R, Eren F, Imeryuz N. Serum osteocalcin levels in patients with nonalcoholic fatty liver disease: association with ballooning degeneration. Scand J Clin Lab Invest. 2011;71:631–636.
    1. Liu JJ, Chen YY, Mo ZN, Tian GX, Tan AH, Gao Y, Yang XB, Zhang HY, Li ZX. Relationship between serum osteocalcin levels and non-alcoholic fatty liver disease in adult males, South China. Int J Mol Sci. 2013;14:19782–19791.
    1. Dou J, Ma X, Fang Q, Hao Y, Yang R, Wang F, Zhu J, Bao Y, Jia W. Relationship between serum osteocalcin levels and non-alcoholic fatty liver disease in Chinese men. Clin Exp Pharmacol Physiol. 2013;40:282–288.
    1. Aller R, Castrillon JL, de Luis DA, Conde R, Izaola O, Sagrado MG, Velasco MC, Alvarez T, Pacheco D. Relation of osteocalcin with insulin resistance and histopathological changes of non alcoholic fatty liver disease. Ann Hepatol. 2011;10:50–55.
    1. Du J, Zhang M, Lu J, Zhang X, Xiong Q, Xu Y, Bao Y, Jia W. Osteocalcin improves nonalcoholic fatty liver disease in mice through activation of Nrf2 and inhibition of JNK. Endocrine. 2016;53:701–709.
    1. Mera P, Laue K, Ferron M, Confavreux C, Wei J, Galán-Díez M, Lacampagne A, Mitchell SJ, Mattison JA, Chen Y, et al. Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise. Cell Metab. 2016;23:1078–1092.
    1. Mera P, Laue K, Wei J, Berger JM, Karsenty G. Osteocalcin is necessary and sufficient to maintain muscle mass in older mice. Mol Metab. 2016;5:1042–1047.
    1. Bugianesi E, Moscatiello S, Ciaravella MF, Marchesini G. Insulin resistance in nonalcoholic fatty liver disease. Curr Pharm Des. 2010;16:1941–1951.
    1. Gaggini M, Morelli M, Buzzigoli E, DeFronzo RA, Bugianesi E, Gastaldelli A. Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Nutrients. 2013;5:1544–1560.
    1. Lallukka S, Yki-Järvinen H. Non-alcoholic fatty liver disease and risk of type 2 diabetes. Best Pract Res Clin Endocrinol Metab. 2016;30:385–395.
    1. De Meyts P. De Groot LJ, Chrousos G, Dungan K, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Endotext [Internet] South Dartmouth (MA): , Inc., 2000-; 2016. The Insulin Receptor and Its Signal Transduction Network.
    1. Cleasby ME, Jamieson PM, Atherton PJ. Insulin resistance and sarcopenia: mechanistic links between common co-morbidities. J Endocrinol. 2016;229:R67–R81.
    1. Guillet C, Zangarelli A, Gachon P, Morio B, Giraudet C, Rousset P, Boirie Y. Whole body protein breakdown is less inhibited by insulin, but still responsive to amino acid, in nondiabetic elderly subjects. J Clin Endocrinol Metab. 2004;89:6017–6024.
    1. Thrailkill KM, Lumpkin CK, Bunn RC, Kemp SF, Fowlkes JL. Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues. Am J Physiol Endocrinol Metab. 2005;289:E735–E745.
    1. Lerchbaum E, Schwetz V, Nauck M, Völzke H, Wallaschofski H, Hannemann A. Lower bone turnover markers in metabolic syndrome and diabetes: the population-based Study of Health in Pomerania. Nutr Metab Cardiovasc Dis. 2015;25:458–463.
    1. Esposito K, Chiodini P, Capuano A, Colao A, Giugliano D. Fracture risk and bone mineral density in metabolic syndrome: a meta-analysis. J Clin Endocrinol Metab. 2013;98:3306–3314.
    1. Laurent MR, Cook MJ, Gielen E, Ward KA, Antonio L, Adams JE, Decallonne B, Bartfai G, Casanueva FF, Forti G, et al. Lower bone turnover and relative bone deficits in men with metabolic syndrome: a matter of insulin sensitivity? The European Male Ageing Study. Osteoporos Int. 2016;27:3227–3237.
    1. Ishii S, Cauley JA, Crandall CJ, Srikanthan P, Greendale GA, Huang MH, Danielson ME, Karlamangla AS. Diabetes and femoral neck strength: findings from the Hip Strength Across the Menopausal Transition Study. J Clin Endocrinol Metab. 2012;97:190–197.
    1. Srikanthan P, Crandall CJ, Miller-Martinez D, Seeman TE, Greendale GA, Binkley N, Karlamangla AS. Insulin resistance and bone strength: findings from the study of midlife in the United States. J Bone Miner Res. 2014;29:796–803.
    1. Szulc P, Varennes A, Delmas PD, Goudable J, Chapurlat R. Men with metabolic syndrome have lower bone mineral density but lower fracture risk--the MINOS study. J Bone Miner Res. 2010;25:1446–1454.
    1. Riddle RC, Clemens TL. Insulin, osteoblasts, and energy metabolism: why bone counts calories. J Clin Invest. 2014;124:1465–1467.
    1. Wei J, Ferron M, Clarke CJ, Hannun YA, Jiang H, Blaner WS, Karsenty G. Bone-specific insulin resistance disrupts whole-body glucose homeostasis via decreased osteocalcin activation. J Clin Invest. 2014;124:1–13.
    1. Pramojanee SN, Phimphilai M, Kumphune S, Chattipakorn N, Chattipakorn SC. Decreased jaw bone density and osteoblastic insulin signaling in a model of obesity. J Dent Res. 2013;92:560–565.
    1. Seki E, Schwabe RF. Hepatic inflammation and fibrosis: functional links and key pathways. Hepatology. 2015;61:1066–1079.
    1. Brenner C, Galluzzi L, Kepp O, Kroemer G. Decoding cell death signals in liver inflammation. J Hepatol. 2013;59:583–594.
    1. Dirks AJ, Leeuwenburgh C. Tumor necrosis factor alpha signaling in skeletal muscle: effects of age and caloric restriction. J Nutr Biochem. 2006;17:501–508.
    1. van Hall G, Steensberg A, Fischer C, Keller C, Møller K, Moseley P, Pedersen BK. Interleukin-6 markedly decreases skeletal muscle protein turnover and increases nonmuscle amino acid utilization in healthy individuals. J Clin Endocrinol Metab. 2008;93:2851–2858.
    1. van Hall G. Cytokines: muscle protein and amino acid metabolism. Curr Opin Clin Nutr Metab Care. 2012;15:85–91.
    1. Beyer I, Mets T, Bautmans I. Chronic low-grade inflammation and age-related sarcopenia. Curr Opin Clin Nutr Metab Care. 2012;15:12–22.
    1. Kwan Tat S, Padrines M, Théoleyre S, Heymann D, Fortun Y. IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev. 2004;15:49–60.
    1. Yilmaz Y, Yonal O, Kurt R, Oral AY, Eren F, Ozdogan O, Ari F, Celikel CA, Korkmaz S, Ulukaya E, et al. Serum levels of osteoprotegerin in the spectrum of nonalcoholic fatty liver disease. Scand J Clin Lab Invest. 2010;70:541–546.
    1. Niu Y, Zhang W, Yang Z, Li X, Fang W, Zhang H, Wang S, Zhou H, Fan J, Qin L, et al. Plasma osteoprotegerin levels are inversely associated with nonalcoholic fatty liver disease in patients with type 2 diabetes: A case-control study in China. Metabolism. 2016;65:475–481.
    1. Rector RS, Thyfault JP. Does physical inactivity cause nonalcoholic fatty liver disease? J Appl Physiol (1985) 2011;111:1828–1835.
    1. Johnson NA, George J. Fitness versus fatness: moving beyond weight loss in nonalcoholic fatty liver disease. Hepatology. 2010;52:370–381.
    1. Keating SE, Hackett DA, George J, Johnson NA. Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol. 2012;57:157–166.
    1. Rolland Y, Czerwinski S, Abellan Van Kan G, Morley JE, Cesari M, Onder G, Woo J, Baumgartner R, Pillard F, Boirie Y, et al. Sarcopenia: its assessment, etiology, pathogenesis, consequences and future perspectives. J Nutr Health Aging. 2008;12:433–450.
    1. Kohrt WM, Bloomfield SA, Little KD, Nelson ME, Yingling VR. American College of Sports Medicine Position Stand: physical activity and bone health. Med Sci Sports Exerc. 2004;36:1985–1996.
    1. Xu J, Lombardi G, Jiao W, Banfi G. Effects of Exercise on Bone Status in Female Subjects, from Young Girls to Postmenopausal Women: An Overview of Systematic Reviews and Meta-Analyses. Sports Med. 2016;46:1165–1182.
    1. Brotto M, Bonewald L. Bone and muscle: Interactions beyond mechanical. Bone. 2015;80:109–114.
    1. Colaianni G, Mongelli T, Colucci S, Cinti S, Grano M. Crosstalk Between Muscle and Bone Via the Muscle-Myokine Irisin. Curr Osteoporos Rep. 2016;14:132–137.
    1. Zhang HJ, Zhang XF, Ma ZM, Pan LL, Chen Z, Han HW, Han CK, Zhuang XJ, Lu Y, Li XJ, et al. Irisin is inversely associated with intrahepatic triglyceride contents in obese adults. J Hepatol. 2013;59:557–562.
    1. Berzigotti A, Saran U, Dufour JF. Physical activity and liver diseases. Hepatology. 2016;63:1026–1040.
    1. Arias-Loste MT, Ranchal I, Romero-Gómez M, Crespo J. Irisin, a link among fatty liver disease, physical inactivity and insulin resistance. Int J Mol Sci. 2014;15:23163–23178.

Source: PubMed

3
Subscribe