Exercise Training Attenuates Non-Alcoholic Fatty Liver Disease in rats with Diabetes via Endoplasmic Reticulum Stress

Abstract

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in type 2 diabetes (T2D). Recent evidence supports that endoplasmic reticulum (ER) stress plays a critical role in the development of NAFLD. Although exercise training has been commonly prescribed for the treatment of NAFLD, the effects of different types of exercise on ER stress in NAFLD under type 2 diabetic condition are largely unknown. PURPOSE: The purpose of this study was to determine the effects of aerobic and resistance exercises on hepatic ER stress response and NAFLD in rats with T2D. METHODS: Male Sprague-Dawley rats were randomly assigned to four groups (n=10/group): Control (CON), T2D, T2D with aerobic exercise (T2D+AE; treadmill walking at 30 m/min, 0° incline, 60 mins/day, 5 day/week, for 8 weeks) and T2D with resistance exercise (T2D+RE; climbing a 80° incline vertical ladder with weights progressively increased from 50% to 100% of maximal carrying capacity on the tail, 3 times/day, 5 days/ week, for 8 weeks). Liver tissue samples were collected for histopathological analysis of the density of lipid droplets, and immunoblot analysis of expression levels of ER stress proteins, including glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), caspase 12, and c-Jun N-terminal kinase (JNK). One-way ANOVAs and Tukey’s -test were used for data analysis. RESULTS: The density of lipid droplets in the liver was significantly higher in the T2D group than in the CON group (p<0.01), but was significantly lower in the T2D+AE and T2D+RE groups when compared to the T2D group (both p<0.01). In addition, the T2D group had significantly higher levels of protein expression of GRP78, CHOP, caspase 12 and JNK when compared to the CON group (all p<0.01). Both exercise groups had significantly lower levels of protein expression of GRP 78, CHOP, Caspase 12 and JNK when compared to the T2D group (p<0.05 to p<0.01). CONCLUSION: Our findings suggest that both aerobic and resistance exercises are protective against NAFLD in rats with T2D by potentially regulating proteins involved in ER stress response.