Exercise during weight loss improves hepatic mitophagy.

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 â€‹< â€‹0.05. COX-IV protein contents were approximately 50% less in HFD compared to LFD. D/PA had 50% more BNIP3 compared to HFD. PINK1 content was 40% higher in D and D/PA compared to LFD. P-PARKIN/PARKIN levels were 40% lower in HFD, D, and D/PA compared to LFD. Whereas p-UbSer65 was 3-fold higher in HFD. LC3II/I ratio was 50% greater in HFD and D/PA, yet p62 protein content was 2.5 fold higher in HFD. High-fat diet causes disruptions in markers of mitochondrial quality control. Physical activity combined with diet were able to ameliorate these derangements and seemingly improve hepatic mitochondrial quality above control values.

The effects of voluntary wheel running during weight-loss on biomarkers of hepatic lipid metabolism and inflammation in C57Bl/6J mice.

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. TGFß1 and BAMBI protein levels were evaluated as biomarkers for hepatic fibrosis. No differences in TGFß1 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.

High-Fructose Intake Impairs the Hepatic Hypolipidemic Effects of a High-Fat Fish-Oil Diet in C57BL/6 Mice.

BACKGROUND: Overnutrition of saturated fats and fructose is one of the major factors for the development of nonalcoholic fatty liver disease. Because omega-3 polyunsaturated fatty acids (n-3fa) have established lipid lowering properties, we tested the hypothesis that n-3fa prevents high-fat and fructose-induced fatty liver disease in mice. METHODS: Male C57BL/6J mice were randomly assigned to one of the following diet groups for 14 weeks: normal diet (ND), high-fat lard-based diet (HFD), HFD with fructose (HFD + Fru), high-fat fish-oil diet (FOD), or FOD + Fru. RESULTS: Despite for the development of obesity and insulin resistance, FOD had 65.3% lower (P < 0.001) hepatic triglyceride levels than HFD + Fru, which was blunted to a 38.5% difference (P = 0.173) in FOD + Fru. The lower hepatic triglyceride levels were associated with a lower expression of lipogenic genes LXRα and FASN, as well as the expression of genes associated with fatty acid uptake and triglyceride synthesis, CD36 and SCD1, respectively. Conversely, the blunted hypotriglyceride effect of FOD + Fru was associated with a higher expression of CD36 and SCD1. CONCLUSIONS: During overnutrition, a diet rich in n-3fa may prevent the severity of hepatic steatosis; however, when juxtaposed with a diet high in fructose, the deleterious effects of overnutrition blunted the hypolipidemic effects of n-3fa.