Nesfatin-1 Acts On The Dorsal Vagal Complex To Inhibit Feeding And To Modulate The Activity Of Glucose-sensing Neurons

Nesfatin-1 is an 82 aminoacid peptide that suppresses food intake after intracere-broventricular injection. Nesfatin-1 (residues 1-82) is a secreted fragment. NUCB2 is cleaved posttranslationally by prohormone convertases into a N-terminus-fragment Nesfatin-1 and two C-terminal peptides, Nesfatin-2 and Nesfatin-3, I.c.v. injection of nesfatin-1 decreases food intake in a dose-dependent manner,whereas injection of an antibody neutralizing nesfatin-1 stimulates appetite. In contrast, i.c.v. injection of other possible fragments processed from NUCB2 does not promote satiety, and conversion of NUCB2 to nesfatin-1 is necessary to induce feeding suppression. Chronic i.c.v. injection of nesfatin-1 reduces body weight, whereas rats gain body weight after chronic i.c.v. injection of an anti-nesfatin-1 antibody Nesfatin-1-induced anorexia occurs in Zucker rats with a leptin receptor mutation, and an anti-nesfatin-1 antibody does not block leptin-induced anorexia. this suggests that NUCB2 is a leptin-independent satiety signaling. In contrast, central injection of a-melanocyte-stimulating hormone elevates NUCB2 gene expression in the paraventricular nucleus, and satiety by nesfatin-1 is abolished by an antagonist of the melanocortin-3/4 receptor. We identify nesfatin-1 as a satiety molecule that is associated with melanocortin signalling in the hypothalamus.Objective To examine the effects of nesfatin-1 on gastric distension sensitive neurons and glucose-responsive neurons in rat dorsal vagal complex(DVC).Methods(1)Electrophysiological recording was adopted to investigate the changes in firing rate of gastric distension neurons and glucose-responsive neurons before and after microinjection of nesfatin-1 into the DVC.(2)Ethology method was adopted to investigate the changes of food intake and body weight before and after microinjection of nesfatin-1 into the DVC.Results (1) The 109 neurons were recorded in DVC, of which 31 were activated by glucose and identified as glucose-excited (glucose-EXC) neurons; 46 were depressed and identified as glucose-inhibited (glucose-INH) neurons; other 32 failed to respond to glucose. Of 26 glucose-excited neurons examined in response to nesfatin-1,20 were activated,3 failed to respond to nesfatin-1. Of 39 glucose-inhibited neurons examined in response to nesfatin-1, 33 were suppressed,1 was activated, and 5 failed to respond to nesfatin-1.(2)Eighty-nine neurons were recorded in DVC,69 of them responded to gastric distension (GD),48 were excited (GD-EXC),21 were inhibited (GD-INH), and 20 failed to respond to GD.32 out of 42 GD-EXC neurons were excited, whereas 16 out of 18 GD-INH neurons were suppressed by nesfatin-1. Two types neurons were failed to respond to 0.9% NaCl.(3)Food intake and body weight decrease after microinjection of nesfatin-1 into the DVC.Conclusion Nesfatin-1 is involved in the modulation the electric activity of GD-sensitive neurons and glucose-responsive neurons in DVC. Our data clearly demonstrate that this newly-discovered peptide may exert at least a part of its physiological actions on the control of food intake as a direct result of its role in controlling the excitability of neurons in the DVC...