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Non-alcoholic fatty liver disease (NAFLD) has recently become a public health concern concurrent with the obesity crisis. Previous work has shown aberrant mitochondrial content/quality and autophagy in models of NAFLD, whereas exercise is known to improve these derangements. The purpose of this study was to examine the effect of different weight-loss modalities on hepatic mitochondrial content, autophagy and mitophagy in NAFLD. Forty-eight male C57BL/6J mice were divided into 1 of 4 groups: low fat diet (LFD, 10% fat, 18 weeks), high fat diet (HFD, 60% fat diet, 18 weeks), weight-loss by diet (D, 60% fat diet for 10 weeks then 10% fat diet for 8 weeks) or weight-loss by diet and physical activity (D/PA, 60% fat diet for 10 weeks, then 10% fat diet plus a running wheel for 8 weeks). Immunoblot data were analyzed by one-way analysis of variance (ANOVA) with significance denoted at p ​

The aim of this study was to determine the effect of voluntary wheel running (VWR) during weight-loss on hepatic lipid and inflammatory biomarkers using a murine model. To induce obesity, male C57Bl/6 mice were fed a 60% high-fat diet (HF) for 10 weeks. At 10 weeks, weight-loss was promoted by randomizing HF-fed mice to a normal diet (ND) either with (WL + VWR) or without (WL) access to running wheels for 8 weeks. Age-matched dietary control mice were fed either a ND or HF for 18 weeks. Following weight-loss, WL + VWR had a lower body mass compared to all groups despite an average weekly caloric consumption comparable to HF mice. WL + VWR had an increased adiponectin concentration when compared to WL, but no difference between WL and WL + VWR was observed for plasma glucose and lipid biomarkers. When compared to HF, the lower hepatic total lipids in both WL and WL + VWR were associated with increased pAMPK:AMPK and reduced pACC-1:ACC-1 ratios. When compared to WL, WL + VWR resulted in lower hepatic cholesterol and trended to lower hepatic triglyceride. In both WL and WL + VWR, pNF-κB p65:NF-κB p65 ratio was lower than HF and comparable to ND. TGFβ1 and BAMBI protein levels were evaluated as biomarkers for hepatic fibrosis. No differences in TGFβ1 was observed between groups; however, WL and WL + VWR had BAMBI protein levels comparable to ND. Overall, the addition of voluntary exercise resulted in greater weight-loss and improvements in hepatic cholesterol and triglyceride levels; however, limited improvements in hepatic inflammation were observed when compared to weight-loss by diet alone.