Central administration of vaspin inhibits glucose production and augments hepatic insulin signaling in high-fat-diet-fed rat

Objective: To investigate the effects of vaspin signaling conveyed by the brain on liver glucose fluxes in rats. Methods: To determine the effects and underlying mechanisms of central vaspin signaling, normal-chow-diet- and high-fat-diet (HFD)-fed rats with or without hepatic branch vagotomy (HBV) received acute infusion of vaspin to the third cerebral ventricle or MK801, a dorsal vagal complex (DVC) N -methyl- D -aspartate (NMDA) receptor inhibitor, to the DVC during the pancreatic euglycemic clamp. Results: Central administration of vaspin in HFD-fed rats significantly increased glucose infusion required to maintain euglycemia owing to an inhibition of glucose production during the clamps. These changes were accompanied by decreased hepatic phosphoenolpyruatecarboxykinase and G6Pase expression levels and increased hepatic insulin receptor, insulin receptor substrate-1, Akt kinase and the forkhead box-containing protein of the O subfamily-1 phosphorylation, suggesting improving hepatic insulin sensitivity in these animals. Conversely, selective HBV or DVC MK-801 infusion in HFD-fed rats blocked the effect of central vaspin on glucose production and hepatic insulin sensitivity. Conclusions: Our findings suggest that brain vaspin inhibited hepatic glucose production and improved insulin sensitivity via DVC to the hepatic branch of the vagus nerve in insulin resistance rats induced by HFD.