title: Nesfatin-1 influences the excitability of glucosensing neurons in the hypothalamic nuclei and inhibits the food intake.
abstract: Nesfatin-1 is a recently discovered neuropeptide that has been shown to decrease food intake after lateral, third, or fourth brain ventricle, cisterna magna administration, or PVN injection in ad libitum fed rats. With regards to the understanding of nesfatin-1 brain sites of action, additional microinjection studies will be necessary to define specific nuclei, in addition to the PVN, responsive to nesfatin-1 to get insight into the differential effects on food intake. In the present study, we evaluated nesfatin-1 action to modulate food intake response upon injection into the specific hypothalamic nuclei (PVN, LHA and VMN) in freely fed rats during the dark phase. We extend previous observations by showing that the nesfatin-1 (50 pmol) injected before the onset of the dark period significantly reduced the 1 to 5 h cumulative food intake in rats cannulated into the PVN, LHA, but not in rats cannulated into the VMN. Glucosensing neurons located in the hypothalamus are involved in glucoprivic feeding and homeostatic control of blood glucose. In order to shed light on the mechanisms by which nesfatin-1 exerts its satiety-promoting actions, we examined the effect of nesfatin-1 on the excitability of hypothalamic glucosensing neurons. Nesfatin-1 excited most of the glucose-inhibited (GI) neurons and inhibited most of the glucose-excited (GE) neurons in the PVN. Of 34 GI neurons in the LHA tested, inhibitory effects were seen in 70.6% (24/34) of GI neurons. The main effects were excitatory after intra-VMN administration of nesfatin-1 in GE neurons (27/35, 77.1%). Thus, our data clearly demonstrate that nesfatin-1 may exert at least a part of its physiological actions on the control of food intake as a direct result of its role in modulating the excitability of glucosensing neurons in the PVN, LHA and VMN.
authors.affiliation: Department of Physiology, Qingdao University School of Medicine, Qingdao 266071, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.forename: Zheng-Yao
authors.initials: ZY
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage / Q000494:pharmacology; D001069:Appetite Regulation / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology; D007026:Hypothalamic Area, Lateral / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D008845:Microinjections / Q000379:methods; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D000080866:Nucleobindins; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism
chemical_list: D001067:Appetite Depressants; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D005947:Glucose