Activation of Nesfatin‐1‐Containing Neurones in the Hypothalamus and Brainstem by Peripheral Administration of Anorectic Hormones and Suppression of Feeding via Central Nesfatin‐1 in Rats

Abstract

Peripheral anorectic hormones, such as glucagon-like peptide (GLP)-1, cholecystokinin (CCK)-8 and leptin, suppress food intake. The newly-identified anorectic neuropeptide, nesfatin-1, is synthesised in both peripheral tissues and the central nervous system, particularly by various nuclei in the hypothalamus and brainstem. In the present study, we examined the effects of i.p. administration of GLP-1 and CCK-8 and co-administrations of GLP-1 and leptin at subthreshold doses as confirmed by measurement of food intake, on nesfatin-1-immunoreactive (-IR) neurones in the hypothalamus and brainstem of rats by Fos immunohistochemistry. Intraperitoneal administration of GLP-1 (100 μg/kg) caused significant increases in the number of nesfatin-1-IR neurones expressing Fos-immunoreactivity in the supraoptic nucleus (SON), the area postrema (AP) and the nucleus tractus solitarii (NTS) but not in the paraventricular nucleus (PVN), the arcuate nucleus (ARC) or the lateral hypothalamic area (LHA). On the other hand, i.p. administration of CCK-8 (50 μg/kg) resulted in marked increases in the number of nesfatin-1-IR neurones expressing Fos-immunoreactivity in the SON, PVN, AP and NTS but not in the ARC or LHA. No differences in the percentage of nesfatin-1-IR neurones expressing Fos-immunoreactivity in the nuclei of the hypothalamus and brainstem were observed between rats treated with saline, GLP-1 (33 μg/kg) or leptin. However, co-administration of GLP-1 (33 μg/kg) and leptin resulted in significant increases in the number of nesfatin-1-IR neurones expressing Fos-immunoreactivity in the AP and the NTS. Furthermore, decreased food intake induced by GLP-1, CCK-8 and leptin was attenuated significantly by pretreatment with i.c.v. administration of antisense nesfatin-1. These results indicate that nesfatin-1-expressing neurones in the brainstem may play an important role in sensing peripheral levels of GLP-1 and leptin in addition to CCK-8, and also suppress food intake in rats.

High-Sugar, but Not High-Fat, Food Activates Supraoptic Nucleus Neurons in the Male Rat

“…Glucagon-like peptide 1 (GLP-1) is also released from the gut in response to nutrients and is thought to mediate a satiety effect through vagal neurones and the NTS (48). The effects of peripheral GLP-1 on the activity of oxytocin neurones have not been well characterised, however peripheral administration of GLP-1 results in c-Fos expression in the SON (49), whereas central injection of GLP-1 induces c-Fos expression in both PVN and SON magnocellular neurones (50). There is evidence for complex effects of GLP-1 on peripheral oxytocin release that depend on the model system and the dose and route of administration (51,52).…”

Oxytocin – The Sweet Hormone?

“…The immediate-early gene c-fos has been extensively used as a marker of neuronal activation, as it is transiently expressed in many neurons following activation. Peripheral administration of GLP-1 induces expression of c-fos in the NTS and the SON but not in the PVN [44], while peripheral administration of the GLP-1 agonist exendin-4 activates c-fos mRNA expression in the arcuate nucleus and parvocellular PVN at low doses, and at higher doses also activates the magnocellular PVN and the SON, effects mediated in part by the vagus [45]. GLP-1 is also expressed in some NTS neurons that project to the PVN and SON, and central administration of GLP-1 increases plasma oxytocin concentration in rats, and suppresses feeding [46].…”

Role of oxytocin in the control of stress and food intake

“…141 Oxytocin neurones have also been shown to be activated by leptin in rats, 142 and reduction of leptin after fasting reduces hypothalamic oxytocin mRNA. 143 Peripheral or central administration of glucagon-like peptide 1 has been reported in rats to activate supraoptic nucleus neurones 144 or hypothalamic paraventricular oxytocin neurones. 145 α-MSH has also been shown to facilitate dendritic oxytocin release but to decrease electrical activity of oxytocin neurones in rats.…”