Mechanisms by which adiponectin reverses high fat diet-induced insulin resistance in mice
Xiruo Li, Dongyan Zhang, Daniel F. Vatner, Leigh Goedeke, Sandro Massao Hirabara, Ye Zhang, Rachel J. Perry, Gerald I. Shulman
Abstract
Significance As it is estimated that one in three Americans will suffer from type 2 diabetes by 2050, interventions to ameliorate insulin resistance are of great interest. Adiponectin has emerged as a promising insulin-sensitizing adipokine; however, the mechanisms by which adiponectin administration improves insulin sensitivity are unclear. Here, we show that globular adiponectin (gAcrp30) and full-length adiponectin (Acrp30) reverse insulin resistance in HFD-fed mice through reductions in ectopic lipid in liver and muscle likely by stimulation of LPL activity in eWAT and increased eNOS/AMPK activation and fat oxidation in muscle. These effects, in turn, lead to decreased plasma membrane diacylglycerol content, resulting in decreased PKCε activation in liver and decreased PKCε/PKCθ activity in muscle and improved insulin signaling in these tissues.