(334d) Resveratrol Releasing 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 had mixed success in clinical trials, in part due to poor bioavailability and patient compliance. To address these issues we encapsulated resveratrol within biodegradable polymeric scaffolds for implant into the adipose tissue, a common target of anti-diabetic drugs. We fabricated scaffolds by encapsulating resveratrol within poly(lactide-co-glycolide) (PLG) microparticles using a single emulsion technique. We then coated sodium chloride crystals with the microparticles and pressed the mixture into a cylindrical disk. Gas foaming followed my repeated washings in water produced an interconnected polymer matrix containing resveratrol (i.e., a scaffold). 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 scaffolds reduce fat gain and improve 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 collected the liver of the mice fourteen days after scaffold implant into the adipose tissue (twenty-one days after beginning the 60% fat diet). Western blot analysis indicated that protein kinase B (PKB or Akt) was elevated in the liver of mice receiving resveratrol scaffold implants compared to controls, suggesting enhanced insulin sensitivity in the liver, which might account for the improved IPGTT performance. Currently, we are investigating gene expression at the implant site to address how scaffolds implanted into the adipose tissue are protecting mice from high fat diets. Collectively, we expect this work to impact our understanding of how biomaterial implant modulates adipose tissue function and aid in the development of new treatments for diabetes, the most common metabolic disorder in the United States.