Modulation of food intake by mTOR signalling in the dorsal motor nucleus of the vagus in male rats: focus on ghrelin and nesfatin-1

New findings center dot What is the central question of this study? Does mammalian target of rapamycin (mTOR) signalling in the dorsal vagal complex contribute to the modulation of energy homeostasis? center dot What is the main finding and its importance? Our study shows, for the first time, that mTOR signalling in neurons of the dorsal motor nucleus of the vagus regulates both the nutrient and the hormonal signals for the modulation of food intake. These results imply that mTOR signalling in the hindbrain may serve as a potential target for treatment of obesity and appetite-related disorders. Previous studies have demonstrated that mammalian target of rapamycin (mTOR) signalling in the hypothalamus is involved in the control of energy homeostasis. The aim of this study was to characterize the effect of mTOR signalling in the dorsal motor nucleus of the vagus (DMNV) on energy intake. Phospho-mTOR was detected in the DMNV neurons, and its levels were increased by energy deprivation. Rapamycin significantly inhibited mTOR activity and reduced food intake when administrated into the fourth ventricle. Exposure of DMNV neurons to ghrelin increased the phosphorylation of mTOR. Injection of ghrelin into the fourth ventricle significantly increased food intake relative to the control vehicle. Pretreatment with rapamycin for 15 min attenuated the orexigenic effect of ghrelin. A reduction in the phosphorylation of mTOR was observed following injection of nesfatin-1 into the fourth ventricle. When administrated by injection into the fourth ventricle, nesfatin-1 suppressed food intake in comparison with the control vehicle. The anorexigenic effect of nesfatin-1 was significantly attenuated by pretreatment with leucine for 15 min. All these findings suggest that mTOR signalling in the DMNV neurons regulates both the nutrient and the hormonal signals for the modulation of food intake.