{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:57:41Z","timestamp":1785437861091,"version":"3.56.0"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["748944"],"award-info":[{"award-number":["748944"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Individuals with hepatic steatosis often display several metabolic abnormalities including insulin resistance and muscle atrophy. Previously, we found that hepatic steatosis results in an altered hepatokine secretion profile, thereby inducing skeletal muscle insulin resistance <jats:italic>via<\/jats:italic> inter-organ crosstalk. In this study, we aimed to investigate whether the altered secretion profile in the state of hepatic steatosis also induces skeletal muscle atrophy <jats:italic>via<\/jats:italic> effects on muscle protein turnover. To investigate this, eight-week-old male C57BL\/6J mice were fed a chow (4.5% fat) or a high-fat diet (HFD; 45% fat) for 12 weeks to induce hepatic steatosis, after which the livers were excised and cut into ~200-\u00b5m slices. Slices were cultured to collect secretion products (conditioned medium; CM). Differentiated L6-GLUT4myc myotubes were incubated with chow or HFD CM to measure glucose uptake. Differentiated C2C12 myotubes were incubated with chow or HFD CM to measure protein synthesis and breakdown, and gene expression <jats:italic>via<\/jats:italic> RNA sequencing. Furthermore, proteomics analysis was performed in chow and HFD CM. It was found that HFD CM caused insulin resistance in L6-GLUT4myc myotubes compared with chow CM, as indicated by a blunted insulin-stimulated increase in glucose uptake. Furthermore, protein breakdown was increased in C2C12 cells incubated with HFD CM, while there was no effect on protein synthesis. RNA profiling of C2C12 cells indicated that 197 genes were differentially expressed after incubation with HFD CM, compared with chow CM, and pathway analysis showed that pathways related to anatomical structure and function were enriched. Proteomics analysis of the CM showed that 32 proteins were differentially expressed in HFD CM compared with chow CM. Pathway enrichment analysis indicated that these proteins had important functions with respect to insulin-like growth factor transport and uptake, and affect post-translational processes, including protein folding, protein secretion and protein phosphorylation. In conclusion, the results of this study support the hypothesis that secretion products from the liver contribute to the development of muscle atrophy in individuals with hepatic steatosis.<\/jats:p>","DOI":"10.3389\/fendo.2021.733625","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T17:01:20Z","timestamp":1634144480000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Hepatic Steatosis Contributes to the Development of Muscle Atrophy via Inter-Organ Crosstalk"],"prefix":"10.3389","volume":"12","author":[{"given":"Kenneth","family":"Pasmans","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel E.","family":"Adriaens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Olinga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Langen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander S.","family":"Rensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank G.","family":"Schaap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven W. M.","family":"Olde Damink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Caiment","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc J. C.","family":"van Loon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen E.","family":"Blaak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth C. R.","family":"Meex","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global Epidemiology of Nonalcoholic Fatty Liver Disease-Meta-Analytic Assessment of Prevalence, Incidence, and Outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20466","article-title":"Prevalence of Hepatic Steatosis in an Urban Population in the United States: Impact of Ethnicity","volume":"40","author":"Browning","year":"2004","journal-title":"Hepatology"},{"key":"B3","article-title":"Liver Pathology in Morbidly Obese Patients With and Without Diabetes","volume":"85","author":"Silverman","year":"1990","journal-title":"Am J Gastroenterol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s11695-017-2980-3","article-title":"Non-Alcoholic Fatty Liver Disease in Morbidly Obese Individuals Undergoing Bariatric Surgery: Prevalence and Effect of the Pre-Bariatric Very Low Calorie Diet","volume":"28","author":"Schwenger","year":"2018","journal-title":"Obes Surg"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-132-2-200001180-00004","article-title":"Prevalence of and Risk Factors for Hepatic Steatosis in Northern Italy","volume":"132","author":"Bellentani","year":"2000","journal-title":"Ann Intern Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.09.023","article-title":"Fetuin B Is a Secreted Hepatocyte Factor Linking Steatosis to Impaired Glucose Metabolism","volume":"22","author":"Meex","year":"2015","journal-title":"Cell Metab"},{"key":"B7","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1080\/17474124.2020.1731303","article-title":"Sarcopenia in Nonalcoholic Fatty Liver Disease: New Challenges for Clinical Practice","volume":"14","author":"El Sherif","year":"2020","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s13539-010-0014-2","article-title":"An Overview of Sarcopenia: Facts and Numbers on Prevalence and Clinical Impact","volume":"1","author":"von Haehling","year":"2010","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-019-09964-1","article-title":"Relationship Between Relative Skeletal Muscle Mass and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis","volume":"14","author":"Cai","year":"2020","journal-title":"Hepatol Int"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13889","article-title":"Sarcopenia Is Associated With Severe Liver Fibrosis in Patients With Non-Alcoholic Fatty Liver Disease","volume":"45","author":"Petta","year":"2017","journal-title":"Aliment Pharmacol Ther"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.08.019","article-title":"Sarcopenia Is an Independent Risk Factor for Non-Alcoholic Steatohepatitis and Significant Fibrosis","volume":"66","author":"Koo","year":"2017","journal-title":"J Hepatol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13166","article-title":"Nonalcoholic Steatohepatitis Is Strongly Associated With Sarcopenic Obesity in Patients With Cirrhosis Undergoing Liver Transplant Evaluation","volume":"31","author":"Carias","year":"2016","journal-title":"J\u00a0Gastroenterol Hepatol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e0186990","DOI":"10.1371\/journal.pone.0186990","article-title":"Prognostic Value of Sarcopenia in Patients With Liver Cirrhosis: A Systematic Review and Meta-Analysis","volume":"12","author":"Kim","year":"2017","journal-title":"PLoS One"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26716","article-title":"Relationship Between Sarcopenia and Nonalcoholic Fatty Liver Disease: The Korean Sarcopenic Obesity Study","volume":"59","author":"Hong","year":"2014","journal-title":"Hepatology"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2013.37.4.278","article-title":"The Role of Skeletal Muscle in Development of Nonalcoholic Fatty Liver Disease","volume":"37","author":"Moon","year":"2013","journal-title":"Diabetes Metab J"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.12506","article-title":"Liver Transplantation Arrests and Reverses Muscle Wasting","volume":"29","author":"Bergerson","year":"2015","journal-title":"Clin Transplant"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2010.111","article-title":"Preparation and Incubation of Precision-Cut Liver and Intestinal Slices for Application in Drug Metabolism and Toxicity Studies","volume":"5","author":"de Graaf","year":"2010","journal-title":"Nat Protoc"},{"key":"B18","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast Universal RNA-Seq Aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"B19","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1186\/1471-2105-12-323","article-title":"RSEM: Accurate Transcript Quantification From RNA-Seq Data With or Without a Reference Genome","volume":"12","author":"Li","year":"2011","journal-title":"BMC Bioinf"},{"key":"B20","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data With Deseq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0183","article-title":"Evidence for Adipose-Muscle Cross Talk: Opposing Regulation of Muscle Proteolysis by Adiponectin and Fatty Acids","volume":"148","author":"Zhou","year":"2007","journal-title":"Endocrinology"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00529.2007","article-title":"Skeletal Muscle Insulin Resistance Induced by Adipocyte-Conditioned Medium: Underlying Mechanisms and Reversibility","volume":"294","author":"Sell","year":"2008","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e0245618","DOI":"10.1371\/journal.pone.0245618","article-title":"Myogenin Is Required for Assembly of the Transcription Machinery on Muscle Genes During Skeletal Muscle Differentiation","volume":"16","author":"Adhikari","year":"2021","journal-title":"PloS One"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.2337\/db14-0796","article-title":"Human Adipocytes Induce Inflammation and Atrophy in Muscle Cells During Obesity","volume":"64","author":"Pellegrinelli","year":"2015","journal-title":"Diabetes"},{"key":"B25","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1038\/s42255-021-00369-9","article-title":"Liver Alanine Catabolism Promotes Skeletal Muscle Atrophy and Hyperglycaemia in Type 2 Diabetes","volume":"3","author":"Okun","year":"2021","journal-title":"Nat Metab"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/ejcn.2009.32","article-title":"Muscle Mass and Functional Correlates of Insulin Sensitivity in Lean Young Indian Men","volume":"63","author":"Unni","year":"2009","journal-title":"Eur J Clin Nutr"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-0251","article-title":"Insulin Resistance Accelerates Muscle Protein Degradation: Activation of the Ubiquitin-Proteasome Pathway by Defects in Muscle Cell Signaling","volume":"147","author":"Wang","year":"2006","journal-title":"Endocrinology"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1053\/j.jrn.2010.05.007","article-title":"Muscle Atrophy in Chronic Kidney Disease Results From Abnormalities in Insulin Signaling","volume":"20","author":"Price","year":"2010","journal-title":"J\u00a0Ren Nutr"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.2337\/db14-0961","article-title":"Lipid-Induced Insulin Resistance Is Associated With an Impaired Skeletal Muscle Protein Synthetic Response to Amino Acid Ingestion in Healthy Young Men","volume":"64","author":"Stephens","year":"2015","journal-title":"Diabetes"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118968","article-title":"Muscle Wasting in Insulinopenic Rats Results From Activation of the ATP-Dependent, Ubiquitin-Proteasome Proteolytic Pathway by a Mechanism Including Gene Transcription","volume":"98","author":"Price","year":"1996","journal-title":"J Clin Invest"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1999.276.5.C1132","article-title":"Evaluation of Signals Activating Ubiquitin-Proteasome Proteolysis in a Model of Muscle Wasting","volume":"276","author":"Mitch","year":"1999","journal-title":"Am J Physiol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118000","article-title":"Protein Dynamics in Whole Body and in Splanchnic and Leg Tissues in Type I Diabetic Patients","volume":"95","author":"Nair","year":"1995","journal-title":"J Clin Invest"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12571","article-title":"Inhibition of Platelet-Derived Growth Factor Signaling Prevents Muscle Fiber Growth During Skeletal Muscle Hypertrophy","volume":"591","author":"Sugg","year":"2017","journal-title":"FEBS Lett"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/mus.22094","article-title":"Structure and Function of the Skeletal Muscle Extracellular Matrix","volume":"44","author":"Gillies","year":"2011","journal-title":"Muscle Nerve"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2004.04.007","article-title":"Focal Adhesion Regulation of Cell Behavior","volume":"1692","author":"Wozniak","year":"2004","journal-title":"Biochim Biophys Acta"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M407517200","article-title":"Insulin-Like Growth Factor-1 (IGF-1) Inversely Regulates Atrophy-Induced Genes via the Phosphatidylinositol 3-Kinase\/Akt\/Mammalian Target of Rapamycin (PI3K\/Akt\/Mtor) Pathway","volume":"280","author":"Latres","year":"2005","journal-title":"J Biol Chem"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-6568(00)00110-8","article-title":"Signalling Aspects of Insulin Resistance in Skeletal Muscle: Mechanisms Induced by Lipid Oversupply","volume":"12","author":"Schmitz-Peiffer","year":"2000","journal-title":"Cell Signal"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00396.2015","article-title":"Prostaglandin E2\/Cyclooxygenase Pathway in Human Skeletal Muscle: Influence of Muscle Fiber Type and Age","volume":"120","author":"Liu","year":"2016","journal-title":"J Appl Physiol (1985)"},{"key":"B39","doi-asserted-by":"publisher","first-page":"e14790","DOI":"10.14814\/phy2.14790","article-title":"Influence of Low-Dose Aspirin, Resistance Exercise, and Sex on Human Skeletal Muscle PGE2\/COX Pathway Activity","volume":"9","author":"Naruse","year":"2021","journal-title":"Physiol Rep"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2020.4507","article-title":"Role of Thrombospondin1 and Thrombospondin2 in Cardiovascular Diseases (Review)","volume":"45","author":"Zhang","year":"2020","journal-title":"Int J Mol Med"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.313105","article-title":"Role of Thrombospondin-1 in Mechanotransduction and Development of Thoracic Aortic Aneurysm in Mouse and Humans","volume":"123","author":"Yamashiro","year":"2018","journal-title":"Circ Res"},{"key":"B42","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/BF00329440","article-title":"Thrombospondin Expression in Traumatized Skeletal Muscle. Correlation of Appearance With Post-Trauma Regeneration","volume":"261","author":"Watkins","year":"1990","journal-title":"Cell Tissue Res"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-009-0077-z","article-title":"The Role of Thrombospondins in Wound Healing, Ischemia, and the Foreign Body Reaction","volume":"3","author":"Kyriakides","year":"2009","journal-title":"J Cell Commun Signal"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00704.2011","article-title":"Annexin A1 Modulates Macula Densa Function by Inhibiting Cyclooxygenase 2","volume":"303","author":"Seidel","year":"2012","journal-title":"Am J Physiol Renal Physiol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M114.039651","article-title":"Proteomic Analysis of the Palmitate-Induced Myotube Secretome Reveals Involvement of the Annexin A1-Formyl Peptide Receptor 2 (FPR2) Pathway in Insulin Resistance","volume":"14","author":"Yoon","year":"2015","journal-title":"Mol Cell Proteomics"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-015-2579-8","article-title":"A Fragmented Form of Annexin A1 Is Secreted From C2C12 Myotubes by Electric Pulse-Induced Contraction","volume":"411","author":"Goto-Inoue","year":"2016","journal-title":"Mol Cell Biochem"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22178","article-title":"Role of Annexin A1 in Mouse Myoblast Cell Differentiation","volume":"224","author":"Bizzarro","year":"2010","journal-title":"J Cell Physiol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"12824","DOI":"10.1038\/s41598-020-69752-y","article-title":"Binding of S100A6 to Actin and the Actin-Tropomyosin Complex","volume":"10","author":"Jurewicz","year":"2020","journal-title":"Sci Rep"},{"key":"B49","doi-asserted-by":"publisher","first-page":"101774","DOI":"10.1016\/j.redox.2020.101774","article-title":"Silencing COX-2 Blocks PDK1\/TRAF4-Induced AKT Activation to Inhibit Fibrogenesis During Skeletal Muscle Atrophy","volume":"38","author":"Chen","year":"2021","journal-title":"Redox Biol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s00109-009-0547-z","article-title":"Phase II Nonrandomized Study of the Efficacy and Safety of COX-2 Inhibitor Celecoxib on Patients With Cancer Cachexia","volume":"88","author":"Mantovani","year":"2010","journal-title":"J Mol Med (Berl)"},{"key":"B51","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1002\/hed.20662","article-title":"Results of a Pilot Study of the Effects of Celecoxib on Cancer Cachexia in Patients With Cancer of the Head, Neck, and Gastrointestinal Tract","volume":"30","author":"Lai","year":"2008","journal-title":"Head Neck"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/nm891","article-title":"Deletion of Cytosolic Phospholipase A2 Promotes Striated Muscle Growth","volume":"9","author":"Haq","year":"2003","journal-title":"Nat Med"},{"key":"B53","doi-asserted-by":"publisher","first-page":"13968","DOI":"10.1038\/s41598-020-70792-7","article-title":"Targeting Cpla2 Derived Lipid Hydroperoxides as a Potential Intervention for Sarcopenia","volume":"10","author":"Pharaoh","year":"2020","journal-title":"Sci Rep"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00247.2010","article-title":"Distinct Protein Degradation Profiles Are Induced by Different Disuse Models of Skeletal Muscle Atrophy","volume":"43","author":"Bialek","year":"2011","journal-title":"Physiol Genomics"},{"key":"B55","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1096\/fj.03-0610com","article-title":"Multiple Types of Skeletal Muscle Atrophy Involve a Common Program of Changes in Gene Expression","volume":"18","author":"Lecker","year":"2004","journal-title":"FASEB J"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.12.031","article-title":"The Role of E3 Ubiquitin-Ligases Murf-1 and Mafbx in Loss of Skeletal Muscle Mass","volume":"98","author":"Rom","year":"2016","journal-title":"Free Radic Biol Med"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01026.2004","article-title":"IL-6-Induced Skeletal Muscle Atrophy","volume":"98","author":"Haddad","year":"2005","journal-title":"J Appl Physiol (1985)"},{"key":"B58","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.it.2014.12.008","article-title":"Versatile Functions for IL-6 in Metabolism and Cancer","volume":"36","author":"Mauer","year":"2015","journal-title":"Trends Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000965RR","article-title":"Extramyocellular Interleukin-6 Influences Skeletal Muscle Mitochondrial Physiology Through Canonical JAK\/STAT Signaling Pathways","volume":"34","author":"Abid","year":"2020","journal-title":"FASEB J"},{"key":"B60","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1186\/s12877-018-1007-9","article-title":"Study on Relationship Between Elderly Sarcopenia and Inflammatory Cytokine IL-6, Anti-Inflammatory Cytokine IL-10","volume":"18","author":"Rong","year":"2018","journal-title":"BMC Geriatr"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-018-0458-0","article-title":"IL-6 Signalling Pathways and the Development of Type 2 Diabetes","volume":"26","author":"Akbari","year":"2018","journal-title":"Inflammopharmacology"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1097\/JES.0b013e3181f44f11","article-title":"Interleukin 6 as a Key Regulator of Muscle Mass During Cachexia","volume":"38","author":"Carson","year":"2010","journal-title":"Exerc Sport Sci Rev"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00340.2020","article-title":"Is REDD1 a Metabolic Double Agent? Lessons From Physiology and Pathology","volume":"319","author":"Britto","year":"2020","journal-title":"Am J Physiol Cell Physiol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2012.20","article-title":"The Impact of Insulin Resistance and Inflammation on the Association Between Sarcopenic Obesity and Physical Functioning","volume":"20","author":"Levine","year":"2012","journal-title":"Obes (Silver Spring)"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200300810","article-title":"Effect of High-Fat Diet on the Expression of Proteins in Muscle, Adipose Tissues, and Liver of C57BL\/6 Mice","volume":"4","author":"Schmid","year":"2004","journal-title":"Proteomics"},{"key":"B66","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jnutbio.2009.11.009","article-title":"Integrated Hepatic Transcriptome and Proteome Analysis of Mice With High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease","volume":"22","author":"Kirpich","year":"2011","journal-title":"J Nutr Biochem"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00074.2008","article-title":"Gene Expression in Human NAFLD","volume":"294","author":"Greco","year":"2008","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20838","article-title":"A Genomic and Proteomic Study of the Spectrum of Nonalcoholic Fatty Liver Disease","volume":"42","author":"Younossi","year":"2005","journal-title":"Hepatology"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.7.1643","article-title":"Interleukin-6 Is a Novel Factor Mediating Glucose Homeostasis During Skeletal Muscle Contraction","volume":"53","author":"Febbraio","year":"2004","journal-title":"Diabetes"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3803\/EnM.2020.658","article-title":"Irisin Regulates the Functions of Hepatic Stellate Cells","volume":"35","author":"Dong","year":"2020","journal-title":"Endocrinol Metab (Seoul)"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.2337\/db08-0245","article-title":"Loss-of-Function Mutation in Myostatin Reduces Tumor Necrosis Factor Alpha Production and Protects Liver Against Obesity-Induced Insulin Resistance","volume":"58","author":"Wilkes","year":"2009","journal-title":"Diabetes"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24097","article-title":"Gender-Specific Differences in Adipose Distribution and Adipocytokines Influence Adolescent Nonalcoholic Fatty Liver Disease","volume":"53","author":"Ayonrinde","year":"2011","journal-title":"Hepatology"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30626","article-title":"Sex Differences in Nonalcoholic Fatty Liver Disease: State of the Art and Identification of Research Gaps","volume":"70","author":"Lonardo","year":"2019","journal-title":"Hepatology"},{"key":"B74","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.3390\/nu11081861","article-title":"Sex-Specific Differences in Fat Storage, Development of Non-Alcoholic Fatty Liver Disease and Brain Structure in Juvenile HFD-Induced Obese Ldlr-\/-.Leiden Mice","volume":"11","author":"Jacobs","year":"2019","journal-title":"Nutrients"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00022.2018","article-title":"High-Fat Diet Overfeeding Promotes Nondetrimental Liver Steatosis in Female Mice","volume":"315","author":"Arisqueta","year":"2018","journal-title":"Am J Physiol Gastrointest Liver Physiol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.733625\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T17:01:26Z","timestamp":1634144486000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.733625\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,11]]},"references-count":75,"alternative-id":["10.3389\/fendo.2021.733625"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2021.733625","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,11]]},"article-number":"733625"}}