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165-OR: The Mechanisms by Which Adiponectin Reverses Insulin Resistance in High-Fat Diet Fed Mice

Adiponectin has emerged as an antidiabetic adipokine, and a potential therapy to treat type 2 diabetes. However, the mechanism by which adiponectin improves insulin sensitivity remains unclear. To address this question, we examined the effects of a 2-week continuous infusion of globular adiponectin (gAcrp30) or saline (CON) on glucose and lipid metabolism in a high fat diet fed (HFD) mouse model. Whole-body and tissue-specific insulin action was assessed by a hyperinsulinemic-euglycemic clamp (HEC). gAcrp30-treated mice displayed reduced fasting plasma glucose and insulin concentrations (both P Conclusion: Taken together these data support the hypothesis that adiponectin improves insulin sensitivity in liver and muscle of HFD fed mice by reducing ectopic lipid (DAG) content in these tissues leading to decreased nPKC activity and increased insulin signaling, and contrary to prior studies, is independent of changes in hepatic ceramide content. Disclosure X. Li: None. D. Zhang: None. R.J. Perry: Research Support; Self; AstraZeneca. D.F. Vatner: None. L. Goedeke: None. Y. Zhang: None. G.I. Shulman: Advisory Panel; Self; AstraZeneca, Janssen Research & Development, Merck & Co., Inc. Advisory Panel; Spouse/Partner; Merck & Co., Inc. Board Member; Self; Novo Nordisk A/S. Consultant; Self; Aegerion Pharmaceuticals, IMetabolic BioPharma Corporation, Longitude Capital, Nimbus Discovery, Inc., Staten Biotechnology B.V. Funding American Heart Association (19PRE34380268); National Institutes of Health (R01DK116774)