title: Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin.
abstract: Current evidence suggests that hypothalamic fatty acid metabolism may play a role in regulating food intake; however, confirmation that it is a physiologically relevant regulatory system of feeding is still incomplete. Here, we use pharmacological and genetic approaches to demonstrate that the physiological orexigenic response to ghrelin involves specific inhibition of fatty acid biosynthesis induced by AMP-activated protein kinase (AMPK) resulting in decreased hypothalamic levels of malonyl-CoA and increased carnitine palmitoyltransferase 1 (CPT1) activity. In addition, we also demonstrate that fasting downregulates fatty acid synthase (FAS) in a region-specific manner and that this effect is mediated by an AMPK and ghrelin-dependent mechanisms. Thus, decreasing AMPK activity in the ventromedial nucleus of the hypothalamus (VMH) is sufficient to inhibit ghrelin's effects on FAS expression and feeding. Overall, our results indicate that modulation of hypothalamic fatty acid metabolism specifically in the VMH in response to ghrelin is a physiological mechanism that controls feeding.
authors.affiliation: Department of Physiology, School of Medicine, University of Santiago de Compostela, S. Francisco s/n, 15782 Santiago de Compostela (A Coruña), Spain. miguellp@usc.es
authors.forename: Miguel
authors.initials: M
authors.lastname: López
authors.forename: Ricardo
authors.initials: R
authors.lastname: Lage
authors.forename: Asish K
authors.initials: AK
authors.lastname: Saha
authors.forename: Diego
authors.initials: D
authors.lastname: Pérez-Tilve
authors.forename: María J
authors.initials: MJ
authors.lastname: Vázquez
authors.forename: Luis
authors.initials: L
authors.lastname: Varela
authors.forename: Susana
authors.initials: S
authors.lastname: Sangiao-Alvarellos
authors.forename: Sulay
authors.initials: S
authors.lastname: Tovar
authors.forename: Kawtar
authors.initials: K
authors.lastname: Raghay
authors.forename: Sergio
authors.initials: S
authors.lastname: Rodríguez-Cuenca
authors.forename: Rosangela M
authors.initials: RM
authors.lastname: Deoliveira
authors.forename: Tamara
authors.initials: T
authors.lastname: Castañeda
authors.forename: Rakesh
authors.initials: R
authors.lastname: Datta
authors.forename: Jesse Z
authors.initials: JZ
authors.lastname: Dong
authors.forename: Michael
authors.initials: M
authors.lastname: Culler
authors.forename: Mark W
authors.initials: MW
authors.lastname: Sleeman
authors.forename: Clara V
authors.initials: CV
authors.lastname: Alvarez
authors.forename: Rosalía
authors.initials: R
authors.lastname: Gallego
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lelliott
authors.forename: David
authors.initials: D
authors.lastname: Carling
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Tschöp
authors.forename: Carlos
authors.initials: C
authors.lastname: Diéguez
authors.forename: Antonio
authors.initials: A
authors.lastname: Vidal-Puig
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D015153:Blotting, Western; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D005215:Fasting / Q000502:physiology; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005247:Feeding Behavior; D054439:Ghrelin / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism* / Q000473:pathology; D017403:In Situ Hybridization; D020738:Leptin / Q000378:metabolism; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019014:fas Receptor
chemical_list: C491899:Fas protein, mouse; D005227:Fatty Acids; D054439:Ghrelin; D020738:Leptin; D019014:fas Receptor; D008316:Malonyl Coenzyme A; D002334:Carnitine O-Palmitoyltransferase; D064429:Fatty Acid Synthases; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases