2,3,5,6-Tetramethylpyrazine improves diet-induced whole-body insulin resistance via suppressing white adipose tissue lipolysis in mice

Abstract

Ectopic lipid accumulation in skeletal muscle and liver arises when nutrient storage systems are exposed to chronic energy surplus, leading to whole-body insulin resistance and metabolic disorders. One recent study has shown 2,3,5,6-tetramethylpyrazine (TMP), highly enriched in roasted foodstuffs, such as cocoa and peanuts, significantly decreases blood lipids levels and ameliorates ApoE-defect induced atherosclerosis suggesting a potent role of TMP in lipid dysregulation improvement. Here, we evaluated the impact of TMP treatment on high fat diet (HFD)-induced insulin resistance. Using hyperinsulinemic-euglycemic mouse clamp, we demonstrated 4-week TMP treatment improved whole-body insulin resistance in HFD-fed mice through suppressing lipolysis in white adipose tissue associated with reduced triglyceride in liver and improved glucose uptake in skeletal muscle. Collectively, our work provides proof-of-concept data to support the development of white adipose tissue-targeted medicine for the treatment of metabolic disorder.