Weight loss enhances hepatic antioxidant status in a NAFLD model induced by high fat diet

Purpose. Nonalcoholic fatty liver disease (NAFLD) is a benign condition that can progress to more severe liver damage in a process mediated, in part, by disturbances in redox balance. Additionally, some argue that it is set to become the main cause of end-stage liver disease in the near future. Here, we investigated whether a diet-induced weight loss is able to reverse hepatic lipid accumulation and to reduce oxidative stress in liver from C57BL/6 mice fed a high-fat (HF) diet. Methods and results. Male C57BL/6 mice were divided into four groups: SC (standard chow, 10% energy from fat, 16 wk); HF (high fat diet, 50% energy from fat, 16 wk); SC-HF (SC 8 wk followed by HF 8 wk); and HF-SC (HF 8 wk followed by SC 8 wk). The HF diet during 8 (SC-HF) and 16 weeks (HF) downregulated mRNA levels and protein expression of Nrf2 and endogenous antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) in the liver, caused liver steatosis, affected liver function markers, increased intra-abdominal and subcutaneous adipose tissue, and induced glucose intolerance and hypercholesterolemia compared to controls (SC). Diet-induced weight loss significantly reduced the intrahepatic lipid accumulation, improved glucose tolerance, and restored both gene and protein expression of the antioxidant enzymes. Conclusion. Our findings suggest that a dietary intervention aimed to induce weight loss may exert protective effects in NAFLD as it can reduce hepatic oxidative stress and intrahepatic lipid accumulation, which can hinder the progression of this condition to more severe states.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author