(237e) Modulation of Adipocyte Size and Fat Pad Weight Via Resveratrol Releasing Scaffolds Implanted into Epididymal Adipose Tissue

Chronic overnutrition leads to lipid accumulation within the adipose tissue which has significant consequences that underlie metabolic diseases. We hypothesized that enhancing lipid catabolism within the adipose tissue is a promising strategy to combat this lipid overload. Treatment with resveratrol, a naturally occurring small molecule, activates fatty acid utilization in adipose tissue; however, a major limitation of this drug is its poor bioavailability. To overcome this challenge, we implanted resveratrol releasing poly(lactide-co-glycolide) (PLG) scaffolds into epididymal fat with the goal of enhancing local lipid catabolism. In this study, lean mice were implanted with resveratrol releasing scaffolds or PLG scaffolds with no drug payload. Resveratrol scaffolds decreased adipocyte size compared to PLG scaffolds, which was also associated with an elevation of AMP kinase activation. Furthermore, based on the results of immunohistochemistry and cell culture experiments, we propose that resveratrol scaffolds decrease adipocyte size due to an increase in lipid utilization of immune cells located at the tissue-material interface. In a follow-up study, resveratrol scaffolds decreased body weight gain, adipose tissue expansion, and adipocyte hypertrophy compared to PLG scaffolds when implanted in mice 4 weeks prior to a high fat diet challenge. Importantly, this scaffold-based strategy required a single administration compared to the daily dosing schedule that is usually required for oral administration. Collectively, this work demonstrates that the use of tissue engineering scaffolds to locally deliver small molecules to the adipose tissue may be a promising strategy to overcome poor drug bioavailability as well as to target key metabolic cells in adipose tissue as a treatment for metabolic disease.