Nesfatin‐1 increases energy expenditure and reduces food intake in rats

Abstract

Objective: Energy homeostasis results from a balance of food intake and energy expenditure, accomplished by the interaction of peripheral and central nervous signals. The recently discovered adipokine nesfatin-1 is involved in the central control of food intake, but whether it also participates in the regulation of thermogenesis is unknown. Methods: Nesfatin-1 was administered intracerebroventricularly to freely moving, male Wistar rats and direct calorimetry was performed to assess its effects on thermogenesis. Furthermore, food intake was measured and hypothalamic and N. tractus solitarius (NTS) neuropeptide expression was determined by quantitative real-time polymerace chain reaction. Leptin, which is involved in both the regulation of food intake and thermogenesis, was used as positive control. Results: For the first time it was shown that central nervous administration of nesfatin-1 profoundly increases thermogenesis in rats to a similar extent as leptin and the role of both peptides in the control of food intake was confirmed. Nesfatin-1 significantly downregulated neuropeptide Y (NPY) mRNA expression in both hypothalamus and NTS. Conclusions: The results strongly support the prominent role of nesfatin-1 for both energy expenditure and food intake and NPY neurons appear to be involved in this effect.

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

“…In agreement with this, in PVN NUCB2-knockdown mice, both peripheral and central administration of leptin failed to induce anorexia (Darambazar et al 2015). Moreover, central co-administration of leptin and nesfatin-1 did not yield larger effects on energy expenditure than nesfatin-1 or leptin alone, possibly suggesting common downstream signaling mechanisms (Wernecke et al 2014). However, when endogenous nesfatin-1 was blocked by the administration of an Ab, leptin was still capable to induce anorexia (Oh-I et al 2006).…”

“…In agreement, rats administered i.c.v. with nesfatin-1 showed decreased Npy mRNA expression in the hypothalamus and NTS (Wernecke et al 2014). Also, NUCB2/nesfatin-1 neurons of the PVN were inhibited by NPY in vitro , confirming that nesfatin-1 and NPY interact within the PVN-ARC-feeding center.…”

“…Nesfatin-1's anorexigenic effect was confirmed in further studies where nesfatin-1 was injected centrally in ad libitum fed rats and mice (Maejima et al 2009, Könczöl et al 2012, Gotoh et al 2013 and fasted animals , Atsuchi et al 2010, Wernecke et al 2014. Only in one study nesfatin-1 failed to suppress light-phase food intake in fasted animals when given into the cisterna magna .…”

“…For instance, the anorexigenic effect induced by nesfatin-1 is blocked by the central administration of the MC3/4 receptor antagonist SHU9119 (Oh-I et al 2006). Contrary to peripheral leptin actions (Huo et al 2006, Perello et al 2007, central or peripheral administration of nesfatin-1 or its midsegment increased proopiomelanocortin (POMC) and cocaine-and amphetamine-related transcript (CART) mRNA expression in the nucleus of the solitary tract (NTS), but not at the hypothalamic level in rats (Oh-I et al 2006, Shimizu et al 2009a, Wernecke et al 2014. The interaction between these two systems is further supported by the finding that α-melanocyte-stimulating hormone (a-MSH) administration increased Nucb2 mRNA expression (Oh-I et al 2006) and activated NUCB2/nesfatin-1 neurons in the PVN.…”

“…Ghrelin and nesfatin-1 are co-expressed in X/A endocrine cells of the gastric mucosa . Ghrelin regulates homeostatic feeding by increasing food intake in both rodents and humans (Wren et al 2000, 2001, Gil-Campos et al 2006). An interaction of nesfatin-1 and ghrelin is also supported by data showing their co-localization in goldfish hypothalamus (Kerbel & Unniappan 2012).…”