title: Differential effects of central ghrelin on fatty acid metabolism in hypothalamic ventral medial and arcuate nuclei.
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.
authors.affiliation: Department of Pediatrics, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB T6G 2S2, Canada.
authors.forename: Su
authors.initials: S
authors.lastname: Gao
authors.forename: Núria
authors.initials: N
authors.lastname: Casals
authors.forename: Wendy
authors.initials: W
authors.lastname: Keung
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Moran
authors.forename: Gary D
authors.initials: GD
authors.lastname: Lopaschuk
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D015153:Blotting, Western; D002262:Carboxy-Lyases / Q000378:metabolism; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D054439:Ghrelin / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000214:Acyl Coenzyme A; D005227:Fatty Acids; D054439:Ghrelin; D012333:RNA, Messenger; C116917:acylcarnitine; D008316:Malonyl Coenzyme A; D002334:Carnitine O-Palmitoyltransferase; D055372:AMP-Activated Protein Kinases; D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase; D002331:Carnitine
keywords: Carnitine palmitoyltransferase; Ghrelin; Hypothalamus; Malonyl-CoA