Nesfatin-1 Influences the Excitability of Glucosensing Neurons in the Dorsal Vagal Complex and Inhibits Food Intake

Nesfatin-1 is a recently discovered metabolic peptide hormone that decreases food intake after lateral, third, or fourth brain ventricle; cisterna magna; or paraventricular nucleus (PVN) injection in ad libitum fed rats. Additional micro-injection studies will improve the understanding of how nesfatin-1 acts on the brain and define specific nuclei responsive to nesfatin-1, which will provide insight on its effects on food intake. We evaluated how nesfatin-1 injection into the dorsal vagal complex (DVC) modulates food intake response in rats during the dark phase. Consistent with previous observations, nesfatin-1-injected rats significantly reduced cumulative food intake over a 5-h period in rats. Chronic administration of nesfatin-1 into the DVC reduced body weight gain over a 10-day period. Because glucosensing neurons in the DVC are involved in glucoprivic feeding and homeostatic control of blood glucose, we examined the effect of nesfatin-1 on the excitability of DVC glucosensing neurons. Nesfatin-1 inhibited most of the glucose-inhibitory (GI) neurons and excited most of the glucose-excitatory (GE) neurons in the DVC. Current-clamp electrophysiology recordings from DVC glucosensing neurons in slice preparation showed that bath applied nesfatin-1(10 nM) increased the firing frequency of GE neurons and inhibited the firing rate of GI-neurons. Nesfatin-1 inhibited 88.9% (16/18) of gastric distension inhibitory (GD-INH) neurons and excited 76.2% (32/42) of gastric distension excitatory (GD-EXC) neurons. Thus, nesfatin-1 may control food intake by modulating the excitability of glucosensing neurons in the DVC.