AUTOPHAGY AND PHYSICAL ACTIVITY IN HEPATIC FUNCTION OF WESTERN DIET-INDUCED OBESITY

Haley Walker1, Megan Rosa1, David Lee1, Jacob Brown1, Lemuel Brown1, Richard Perry Jr1, Tyrone Washington1, Nicholas Greene1; 1Univeristy of Arkansas, Fayetteville, AR; e-mail: haw005@uark.edu Obesity is a known risk factor promoting the development fatty diver disease. In the United States, non-alcoholic Fatty Liver Disease (NAFLD) is key contributor for the dramatic rise in liver derangements. NAFLD is often the initial manifestation of liver malfunction, and can progress into further liver detriments such as steatosis, and cirrhosis. With no known pharmacological solution, further investigation has gone into selective autophagy due to its known effects on hepatic health and maintenance of cellular functioning. Purpose: The purpose of this study was to investigate regulation of autophagy in liver following Western Diet-induced obesity and 4 weeks voluntary physical activity. Methods: Forty C57BL/6J mice were divided into two groups and fed Western Diet (WD) or normal chow (NC) for 4 weeks; afterwards, the groups were further divided into voluntary wheel running (VWR) or sedentary (SED) conditions for an additional 4 weeks while on assigned diet. VWR animals were given a free moving running wheel. At 16 weeks of age, animals were euthanized and livers were collected and snap-frozen in liquid nitrogen. Livers were homogenized and analyzed for mRNA and protein content of autophagy markers. Data was analyzed via 2X2 ANOVA with a Tukey-Kramer post hoc adjustment, α was set at 0.05. Results: mRNA of autophagy machinery Beclin was approximately 50% lower in WD-SED and WD-VWR compared to controls. Bnip3, a marker of mitochondrial specific autophagy, mRNA content was 75% lower in WD-SED compared to controls. BNIP3 protein content was 30% less in WD animals compared to NC animals. Basal autophagy flux was increased in VWR animals as measured by LC3II/I ratio and p62 protein content. Yet, WD animals exhibited lower total content of LC3, possibly suggesting a reduced autophagy capacity. Conclusions: Our data demonstrate apparent reductions in autophagic capacity following WD-induced obesity. We are the first, however, to provide evidence of physical activity-induced enhanced autophagic flux. This study provides evidence for moderate physical activity promotion of autophagy flux in the liver, potentially helping to prevent liver derangements