(194aa) Resveratrol Loaded Scaffolds Protect Mice Against Diet Induced Obesity and Glucose Intolerance

Despite current treatments, the number of people diagnosed with type 2 diabetes continues to rise, demonstrating a need for new therapeutic strategies. Resveratrol, a natural polyphenol found in the skin of red grapes, has come into the spotlight as a promising anti-diabetic agent after success in many preclinical diabetes models; however, oral and intravenous administration have failed to translate in clinical trials likely due to poor bioavailability and patient compliance. To address these issues, we have encapsulated resveratrol within biodegradable polymeric scaffolds for implant into the adipose tissue, an integral tissue in the pathogenesis of type 2 diabetes. We fabricated scaffolds by first encapsulating resveratrol within poly(lactide-co-glycolide) (PLG) particles using a single emulsion technique. We then mixed the particles with sodium chloride, a sacrificial porogen, and pelleted the mixture in a die. The pellet is gas foamed in CO2 and then washed in water, leaving behind a polymer matrix containing resveratrol. Scaffolds integrate with the epididymal adipose tissue of C57BL/6 mice within seven days after implant and histological analysis indicates the polymer matrix is in contact with adipocytes. Interestingly, resveratrol scaffold implant reduces fat gain and improves glucose intolerance caused by a 60% fat diet as measured by dual-energy x-ray absorptiometry and an intraperitoneal glucose tolerance test (IPGTT), respectively. To address how scaffolds are working, we characterized the secretome at the implant site for changes in expression of adipokines that promote metabolic health and gene expression in the liver and skeletal muscle, target tissues of these adipokines. Our results indicate insulin mimicking and sensitizing adipokines are upregulated at the implant site and correlate with increased expression of glucose transporter molecules in the skeletal muscle and insulin signaling in the liver. This presentation will detail the mechanism of how we believe resveratrol scaffolds are modulating whole body metabolism in the mouse. Collectively, we expect this work to elucidate how biomaterial implants can be used as drug delivery vehicles to modulate adipose tissue function and aid in the development of new treatments for diabetes, the most common metabolic disorder in the United States.