Differential effects of central ghrelin on fatty acid metabolism in hypothalamic ventral medial and arcuate nuclei

• Published in: Physiology & behavior 2013-06, Vol.118, p.165-170
• Main Authors: Gao, Su, Casals, Núria, Keung, Wendy, Moran, Timothy H, Lopaschuk, Gary D
• Format: Article
• Language: English
• Subjects: Acyl Coenzyme A - metabolism; AMP-activated protein kinase; AMP-Activated Protein Kinases - metabolism; Animals; Arcuate Nucleus of Hypothalamus - drug effects; Arcuate Nucleus of Hypothalamus - metabolism; Behavioral psychophysiology; beta oxidation; biochemical pathways; Biological and medical sciences; Blotting, Western; Carboxy-Lyases - metabolism; Carnitine - analogs & derivatives; Carnitine - metabolism; Carnitine O-Palmitoyltransferase - metabolism; Carnitine palmitoyltransferase; fatty acid metabolism; fatty acids; Fatty Acids - metabolism; food intake; Fundamental and applied biological sciences. Psychology; Ghrelin; Ghrelin - administration & dosage; Ghrelin - pharmacology; Hypothalamus; Injections, Intraventricular; Lipid Metabolism - drug effects; Male; Malonyl Coenzyme A - metabolism; Malonyl-CoA; phosphorylation; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Ventromedial Hypothalamic Nucleus - drug effects; Ventromedial Hypothalamic Nucleus - metabolism
• ISSN: 0031-9384; 1873-507X
• DOI: 10.1016/j.physbeh.2013.03.030

Abstract Fatty acid metabolism is an important pathway involved in the hypothalamus-mediated control of food intake. Previous studies using whole hypothalamic tissue lysates have shown that fatty acid metabolism plays a key role in ghrelin's effect on feeding. Here, we report site-specific effects of central ghrelin on fatty acid metabolism in two critical hypothalamic nuclei, the ventral medial nucleus (VMN) and the arcuate nucleus (Arc). Intracerebroventricular administration of ghrelin to rats activates AMP-activated protein kinase in both the VMN and the Arc, while ghrelin treatment has a site-specific effect on fatty acid metabolic pathways in these two nuclei. In the VMN, central ghrelin increases the phosphorylation level of ACC, indicating the decrease in activity, and decreases the level of malonyl-CoA (the product of ACC). Malonyl-CoA is an inhibitor of carnitine palmitoyltransferase-1 (CPT-1) that is a key enzyme in mitochondrial fatty acid oxidation. Consistent with this action of malonyl-CoA on CPT-1, central ghrelin treatment increases the activity of CPT-1 in the VMN. In contrast, in the Arc, neither malonyl-CoA level nor CPT-1 activity is affected following central ghrelin. Taken together, our data suggest ghrelin exerts differential effects on fatty acid metabolic pathways in the VMN and the Arc.