The effects of nesfatin‐1 in the paraventricular nucleus on gastric motility and its potential regulation by the lateral hypothalamic area in rats

Abstract

The current study investigated the effects of nesfatin-1 in the hypothalamic paraventricular nucleus (PVN) on gastric motility and the regulation of the lateral hypothalamic area (LHA). Using single unit recordings in the PVN, we show that nesfatin-1 inhibited the majority of the gastric distention (GD)-excitatory neurons and excited more than half of the GD-inhibitory (GD-I) neurons in the PVN, which were weakened by oxytocin receptor antagonist H4928. Gastric motility experiments showed that administration of nesfatin-1 in the PVN decreased gastric motility, which was also partly prevented by H4928. The nesfatin-1 concentration producing a half-maximal response (EC50) in the PVN was lower than the value in the dorsomedial hypothalamic nucleus, while nesfatin-1 in the reuniens thalamic nucleus had no effect on gastric motility. Retrograde tracing and immunofluorescent staining showed that nucleobindin-2/nesfatin-1 and fluorogold double-labeled neurons were observed in the LHA. Electrical LHA stimulation changed the firing rate of GD-responsive neurons in the PVN. Pre-administration of an anti-nucleobindin-2/nesfatin-1 antibody in the PVN strengthened gastric motility and decreased the discharging of the GD-I neurons induced by electrical stimulation of the LHA. These results demonstrate that nesfatin-1 in the PVN could serve as an inhibitory factor to inhibit gastric motility, which might be regulated by the LHA.

Nucleobindin-2/Nesfatin-1 in the Human Hypothalamus Is Reduced in Obese Subjects and Colocalizes with Oxytocin, Vasopressin, Melanin-Concentrating Hormone, and Cocaine- and Amphetamine-Regulated Transcript

“…In this study, the prominent immunoexpression of NUCB2/nesfatin-1 in the PVN, SON, IFN, and LHA is in agreement with neuroanatomical evidence and functional analyses from animal studies, revealing that NUCB2/nesfatin-1 effects on energy homeostasis are primarily mediated by PVN, SON, Arc (IFN), and LHA NUCB2/nesfatin-1 [3, 5-10, 21, 29-31, 33, 42-44]. NUCB2/nesfatin-1 localization pattern in human hypothalamic nuclei is indicative of a potential function for NUCB2/nesfatin-1 as an integral regulator of energy homeostasis; moreover, it could imply a role for NUCB2/nesfatin-1 in the regulation of other neuroendocrine and autonomic functions, which will require further studies in humans.…”

Nesfatin-1: functions and physiology of a novel regulatory peptide

“…When administered into the PVN, nesfatin-1 dose-dependently decreased gastric motility and emptying, an effect mediated by oxytocinergic neurons (Guo et al 2015). Similarly, when injected into the ARC, CeA or BMA, nesfatin-1 decreased gastric motility and emptying by exploiting the melanocortin system (Li et al 2013b, Wang et al 2014, Xu et al 2015a).…”

“…Similarly, when injected into the ARC, CeA or BMA, nesfatin-1 decreased gastric motility and emptying by exploiting the melanocortin system (Li et al 2013b, Wang et al 2014, Xu et al 2015a). Strikingly, the endogenous level of NUCB2/nesfatin-1 seems to be important in the physiological regulation of gastric functions as anti-NUCB2/nesfatin-1 Ab application is also capable to alter the activity of PVN, ARC, CeA and BMA gastric distensionsensitive neurons (Li et al 2013b, Wang et al 2014, Guo et al 2015, Xu et al 2015a.…”

Increased concentrations of serum nesfatin-1 levels in childhood with idiopathic chronic malnutrition

“…Several studies have shown that nesfatin-1 plays a role in the inhibition of food intake by leading to hyperpolarization in arcuate nuclei, which is responsible for neuropeptide-Y (an orexigenic protein) secretion (7)(8)(9). Moreover, experimental studies demonstrated that increased nesfatin-1 reduces appetite by reducing gastric motility and consequently leads to malnutrition (10,11). To date, there have been two studies that investigated the relation between nesfatin-1 and childhood malnutrition and the results were conflicting (12,13).…”