Abstract

Nesfatin-1 is well-established to induce an anorexigenic effect. Recently, nesfatin-130−59, was identified as active core of full length nesfatin-11−82 in mice, while its role in rats remains unclear. Therefore, we investigated the effects of nesfatin-130−59 injected intracerebroventricularly (icv) on the food intake microstructure in rats. To assess whether the effect was also mediated peripherally we injected nesfatin-130−59 intraperitoneally (ip). Since obesity affects the signaling of various food intake-regulatory peptides we investigated the effects of nesfatin-130−59 under conditions of diet-induced obesity (DIO). Male Sprague–Dawley rats fed ad libitum with standard diet were icv cannulated and injected with vehicle (5 μl ddH2O) or nesfatin-130−59 at 0.37, 1.1, and 3.3 μg (0.1, 0.3, 0.9 nmol/rat) and the food intake microstructure assessed using a food intake monitoring system. Next, naïve rats were injected ip with vehicle (300 μl saline) or nesfatin-130−59 (8.1, 24.3, 72.9 nmol/kg). Lastly, rats were fed a high fat diet for 10 weeks and those developing DIO were icv cannulated. Nesfatin-1 (0.9 nmol/rat) or vehicle (5 μl ddH2O) was injected icv and the food intake microstructure assessed. In rats fed standard diet, nesfatin-130−59 caused a dose-dependent reduction of dark phase food intake reaching significance at 0.9 nmol/rat in the period of 4–8 h post injection (−29%) with the strongest reduction during the fifth hour (−75%), an effect detectable for 24 h (−12%, p < 0.05 vs. vehicle). The anorexigenic effect of nesfatin-130−59 was due to a reduction in meal size (−44%, p < 0.05), while meal frequency was not altered compared to vehicle. In contrast to icv injection, nesfatin-130−59 injected ip in up to 30-fold higher doses did not alter food intake. In DIO rats fed high fat diet, nesfatin-130−59 injected icv reduced food intake in the third hour post injection (−71%), an effect due to a reduced meal frequency (−27%, p < 0.05), while meal size was not altered. Taken together, nesfatin-130−59 is the active core of nesfatin-11−82 and acts centrally to reduce food intake in rats. The anorexigenic effect depends on the metabolic condition with increased satiation (reduction in meal size) under normal weight conditions, while in DIO rats satiety (reduction in meal frequency) is induced.

Highlights

  • Nesfatin-11−82 was discovered in 2006 by Mori et al as an anorexigenic peptide derived from the rat brain (Oh-I et al, 2006)

  • Since the hypothalamic regulation of food intake is altered under conditions of diet-induced obesity (DIO) (Velloso and Schwartz, 2011), we investigated the effect of nesfatin-130−59 on the food intake microstructure in chronically icv cannulated DIO rats accustomed to the food intake monitoring system and fed a high fat diet

  • Analysis of hourly food intake indicated that the main anorexigenic effect occurred during the fifth hour post injection with a −75% reduction of food intake following nesfatin130−59 compared to vehicle (p = 0.05; Figure 2)

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Summary

Introduction

Nesfatin-11−82 was discovered in 2006 by Mori et al as an anorexigenic peptide derived from the rat brain (Oh-I et al, 2006). The anorexigenic effect of central nesfatin-11−82 injected into the lateral, third and fourth brain ventricle, into the cisterna magna or directly into the lateral hypothalamic area, the paraventricular nucleus, or the dorsal vagal complex has been confirmed by various independent groups in several studies in rats (Yosten and Samson, 2009, 2010; Chen et al, 2012; Könczöl et al, 2012; Xia et al, 2012; Dong et al, 2014), mice (Atsuchi et al, 2010; Goebel et al, 2011), and goldfish (Gonzalez et al, 2010; Kerbel and Unniappan, 2012) This converging evidence points toward a physiological role of nesfatin-11−82 in the regulation of food intake

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