Abstract
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.
Highlights
Nesfatin-1, an 82-amino-acid peptide derived from the nucleobindin 2 (NUCB2), is emerging as a new regulator of food intake [1] and is expressed in several regions of the brain, including the paraventricular nucleus of the hypothalamus (PVN), supraoptic nucleus (SON), arcuate nucleus (ARC), lateral hypothalamic area (LHA), zona incerta, and the nucleus of the solitary tract (NTS), a medullary structure that plays an important role in the regulation of feeding [2,3,4,5]
Numerous structures, including hypothalamic nuclei and the medullary dorsal vagal complex (DVC) which is composed of 3 parts: the area postrema (AP), NTS and dorsal motor nucleus of the vagus nerve (DMNV) belong to the brain vagal-regulatory pathway activated during hypoglycemia and contain a large proportion of nesfatin-1-expressing neurons [11]
Studies have focused on the role of nesfatin-1 in the hypothalamic nuclei regulating food intake, few have investigated the role of nesfatin-1 in the DVC
Summary
Nesfatin-1, an 82-amino-acid peptide derived from the nucleobindin 2 (NUCB2), is emerging as a new regulator of food intake [1] and is expressed in several regions of the brain, including the paraventricular nucleus of the hypothalamus (PVN), supraoptic nucleus (SON), arcuate nucleus (ARC), lateral hypothalamic area (LHA), zona incerta, and the nucleus of the solitary tract (NTS), a medullary structure that plays an important role in the regulation of feeding [2,3,4,5]. A recent study by Maejima et al [8] shows that administering nesfatin-1 into the 3v induces c-Fos expression in the PVN and NTS, and focal injection of nesfatin-1 into the PVN induces c-Fos expression in the NTS This selective c-Fos induction indicates these nuclei are likely involved in anorectic signaling by nesfatin-1. Subgroups of hindbrain catecholamine neurons selectively activated by hypoglycemic stimuli play a significant role in feeding and hyperglycemic responses to a glucose deficit [12,13,14]. Glucosensing neurons alter their action potential frequency responding to the changes in extracellular glucose concentration and initiate the counterregulatory response to hypoglycemia. DVC contains two kinds of glucosensing neurons, glucose-excited (GE)
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