Chronic oral rapamycin decreases adiposity, hepatic triglycerides and insulin resistance in male mice fed a diet high in sucrose and saturated fat

Aims/hypothesis: Excess adiposity is commonly associated with insulin resistance, which can increase the risk of cardiovascular disease. However, the exact molecular mechanisms by which obesity results in insulin resistance are yet to be clearly understood. The intracellular nutrient sensing protein, mechanistic target of rapamycin (mTOR), is a critical signaling component in the development of obesity-associated insulin resistance. Since increased tissue activation of mTOR complex-1 (mTORC1) occurs in obesity, diabetes, and aging, we hypothesized that pharmacologic inhibition of mTORC1 would improve metabolic dysregulation in diet-induced obesity.