(625b) Resveratrol Loaded PLG Scaffolds Prevent Accumulation of Epididymal Adipose Tissue after High Fat Diet Challenge

Authors: 
Murphy, K., University of South Carolina
Gower, M., University of South Carolina
Hendley, M., University of South Carolina
Isely, C., University of South Carolina
The incidence of obesity has only continued to rise and is undoubtedly a significant health care concern in the United States. The standard treatment plan for obesity includes dietary changes and exercise. However, there are cases when lifestyle interventions are minimally effective due to extremity of the disease and issues with patient compliance. The use of resveratrol, a naturally occurring small molecule, as a pharmaceutical intervention for obesity is a promising strategy as resveratrol induces signaling pathways that mimic caloric restriction and exercise, which ultimately reduce fat mass. However, a major limitation of this drug is its poor bioavailability. When taken orally, resveratrol is quickly metabolized in the gut preventing high concentrations of the molecule in target tissues; therefore, extremely high doses must be taken frequently to see effects. Research shows that the need for daily administrations of a drug decreases patient compliance and therapeutic efficacy. Therefore, our strategy to bypass this issue is to deliver the drug locally, once, using a poly(lactide-co-glycolide) (PLG) scaffold designed for extended release of resveratrol. Based on the molecular targets of resveratrol, we tested the hypothesis that local delivery of this drug to the epididymal fat pad would increase fatty acid utilization and protect mice from high fat diet induced weight gain. Briefly, mice were implanted with resveratrol or “blank” scaffolds into the epididymal fat. Mice that only received the surgery, but no biomaterial implant were included for comparison and are referred to as “sham” mice. Four weeks after scaffold implant, mice were challenged with a high fat diet for 4 weeks and then euthanized. The epididymal fat pad of mice that received resveratrol scaffolds was approximately 50% smaller at the end of the study compared to those that received either blank scaffolds or sham surgery. Food measurements taken throughout the 4 week diet indicate that this effect was not due to decreased food intake. This presentation will focus on the expression and activation of key players involved in fatty acid oxidation throughout the timeframe of the study. Furthermore, we will present how resveratrol scaffolds affect adipose tissue remodeling that could play a role in fatty acid utilization. Collectively, this work will demonstrate the novel use of local resveratrol delivery via PLG scaffolds to modulate fatty acid utilization as a protective strategy against diet induced obesity.