title: Moderate physical activity promotes basal hepatic autophagy in diet-induced obese mice.
abstract: Obesity is a known risk factor for the development of hepatic disease; obesity-induced fatty liver can lead to inflammation, steatosis, and cirrhosis and is associated with degeneration of the mitochondria. Lifestyle interventions such as physical activity may ameliorate this condition. The purpose of this study was to investigate regulation of mitochondrial and autophagy quality control in liver following Western diet-induced obesity and voluntary physical activity. Eight-week-old C57BL/6J mice were fed a Western diet (WD) or normal chow (NC, control) for 4 weeks; afterwards, groups were divided into voluntary wheel running (VWR) or sedentary (SED) conditions for an additional 4 weeks. WD-SED animals had a median histology score of 2, whereas WD-VWR was not different from NC groups (median score 1). There was no difference in mRNA of inflammatory markers Il6 and Tnfa in WD animals. WD animals had 50% lower mitochondrial content (COX IV and Cytochrome C proteins), 50% lower Pgc1a mRNA content, and reduced content of mitochondrial fusion and fission markers. Markers of autophagy were increased in VWR animals, regardless of obesity, as measured by 50% greater LC3-II/I ratio and 40% lower p62 protein content. BNIP3 protein content was 30% less in WD animals compared with NC animals, regardless of physical activity. Diet-induced obesity results in derangements in mitochondrial quality control that appear to occur prior to the onset of hepatic inflammation. Moderate physical activity appears to enhance basal autophagy in the liver; increased autophagy may provide protection from hepatic fat accumulation.
authors.affiliation: a Integrative Muscle Metabolism Laboratory, Human Performance Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR 72701, USA.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Rosa-Caldwell
authors.affiliation: a Integrative Muscle Metabolism Laboratory, Human Performance Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR 72701, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Lee
authors.affiliation: a Integrative Muscle Metabolism Laboratory, Human Performance Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR 72701, USA.
authors.forename: Jacob L
authors.initials: JL
authors.lastname: Brown
authors.affiliation: b Exercise Muscle Biology Laboratory, Human Performance Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR 72701, USA.
authors.forename: Lemuel A
authors.initials: LA
authors.lastname: Brown
authors.affiliation: b Exercise Muscle Biology Laboratory, Human Performance Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR 72701, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Perry
authors.affiliation: c Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Greene
authors.affiliation: d California Animal Health and Food Safety Laboratory, University of California-Davis School of Veterinary Medicine, Davis, CA 95616, USA.
authors.forename: Francisco R
authors.initials: FR
authors.lastname: Carvallo Chaigneau
authors.affiliation: b Exercise Muscle Biology Laboratory, Human Performance Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR 72701, USA.
authors.forename: Tyrone A
authors.initials: TA
authors.lastname: Washington
authors.affiliation: a Integrative Muscle Metabolism Laboratory, Human Performance Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR 72701, USA.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Greene
mesh_terms: D000818:Animals; D000071182:Autophagosomes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001343:Autophagy; D015415:Biomarkers / Q000378:metabolism; D066273:Diet, Western / Q000009:adverse effects; D005786:Gene Expression Regulation; D006529:Hepatomegaly / Q000209:etiology / Q000517:prevention & control; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D063306:Mitophagy; D009043:Motor Activity; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology*; D009765:Obesity / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse
keywords: diabetes; diabète; exercice physique; exercise; insulin resistance; insulinorésistance; mitochondria; mitochondries; nonalcoholic fatty liver disease; stéatose hépatique non alcoolique