A role of nesfatin-1/NucB2 in dehydration-induced anorexia

Abstract

Nesfatin-1/NucB2, an anorexigenic molecule, is expressed mainly in the hypothalamus, particularly in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN). Nesfatin-1/NucB2 is also expressed in the subfornical organ (SFO). Because the SON and PVN are involved in body fluid regulation, nesfatin-1/NucB2 may be involved in dehydration-induced anorexia. To clarify the effects of endogenous nesfatin-1/NucB2, we studied changes in nesfatin-1/NucB2 mRNA levels in the SFO, SON, and PVN in adult male Wistar rats after exposure to osmotic stimuli by using in situ hybridization histochemistry. Significant increases in nesfatin-1/NucB2 mRNA levels, ∼2- to 3-fold compared with control, were observed in the SFO, SON, and PVN following water deprivation for 48 h, consumption of 2% NaCl hypertonic saline in drinking water for 5 days, and polyethylene glycol-induced hypovolemia. In addition, nesfatin-1/NucB2 expression was increased in response to water deprivation in a time-dependent manner. These changes in nesfatin-1/NucB2 mRNA expression were positively correlated with plasma sodium concentration, plasma osmolality, and total protein levels in all of the examined nuclei. Immunohistochemistry for nesfatin-1/NucB2 revealed that nesfatin-1/NucB2 protein levels were also increased after 48 h of dehydration and attenuated by 24 h of rehydration. Moreover, intracerebroventricular administration of nesfatin-1/NucB2-neutralizing antibody after 48 h of water deprivation resulted in a significant increase in food intake compared with administration of vehicle alone. These results suggested that nesfatin-1/NucB2 is a crucial peptide in dehydration-induced anorexia.

Anorexia in human and experimental animal models: physiological aspects related to neuropeptides

“…Moreover, i.c.v. injection of nesfatin-1 neutralizing antibody after 48 h water deprivation resulted in an almost complete cancelling of the anorexia induced by dehydration [10]. These results suggest that nesfatin-1 is one of the potential candidates involved in the development of anorexia induced by dehydration.…”

“…To resolve this problem, several groups have proposed the use of dehydration-induced anorexia in animal models [10,[89][90][91]. Dehydration-induced anorexia involves an important physiological adaptation that limits the intake of osmolytes from food and helps maintain the integrity of fluid compartments [92].…”

“…We have previously demonstrated that the gene expression of nesfatin-1 in the PVN is also up-regulated in rats dehydrated for 2 days or drinking hypertonic saline (2 % NaCl) for 5 days instead of drinking tap water [10]. Dehydration causes hyperosmolality and hypovolemia.…”

“…Various types of physiological and pathophysiological anorexia models have been proposed, although these models are not the same model as human anorexia because of its complexities of biological, psychological and/or environmental abnormalities. The typical models of physiological anorexia are dehydrationinduced anorexia and stress-induced anorexia [9][10][11][12]. On the other hand, the typical models of pathophysiological anorexia are drug-induced anorexia, lipopolysaccharides (LPS)-induced anorexia, anti-cancer drug-induced anorexia as a side effect and cancer-induced cachexia-anorexia [13][14][15].…”

Paraventricular NUCB2/Nesfatin-1 Supports Oxytocin and Vasopressin Neurons to Control Feeding Behavior and Fluid Balance in Male Mice

“…Coronal sections (40 m) of the hypothalamus were cut using a freezing microtome and collected at 120 m intervals. After blocking of endogenous peroxidase, sections were incubated with rabbit anti-NUCB2 primary antibody (1:1000; Sigma-Aldrich) (18,21) or antioxytocin primary antibody (1:1000; Chemicon) (15) overnight at 4°C (Table 1). Primary antibodies were detected using a VECTASTAIN ABC kit (Vector Labs).…”