Ghrelin enhances food intake and carbohydrate oxidation in a nitric oxide dependent manner

In the present study we sought to investigate interactions between hypothalamic nitric oxide (NO) and ghrelin signaling on food intake and energy substrate utilization as measured by the respiratory exchange ratio (RER). Guide cannulae were unilaterally implanted in either the arcuate (ArcN) or paraventricular (PVN) nuclei of male Sprague-Dawley rats. Animals were pretreated with subcutaneous (2.5-10 mg/kg/ml) or central (0-100 pmol) N-nitro-l-Arginine methyl ester (l-NAME) followed by 50 pmol of ghrelin administered into either the ArcN or PVN. Both l-NAME and ghrelin were microinjected at the onset of the active cycle and food intake and RER were assessed 2 h postinjection. RER was measured as the ratio of the volume of carbon dioxide expelled relative to the volume of oxygen consumed (VCO2/VO2) using an open-circuit indirect calorimeter. Our results demonstrated that peripheral and central l-NAME pretreatment dose-dependently attenuated ghrelin induced increases in food intake and RER in either the ArcN or PVN. In fact the 100 pmol dose largely reversed the metabolic effects of ghrelin in both anatomical regions. These findings suggest that ghrelin enhancement of food intake and carbohydrate oxidation in the rat ArcN and PVN is NO-dependent.