TY - JOUR
T1 - Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin
AU - Lopez, Miguel
AU - Lage, Ricardo
AU - Saha, Asish K
AU - Perez-Tilve, Diego
AU - Vazquez, Maria
AU - Varela, Luis
AU - Sangiao-Alvarellos, Susana
AU - Tovar, Sulay
AU - Raghay, Kawtar
AU - Rodriguez-Cuenca, Sergio
AU - Deoliveira, Rosangela M
AU - Castaneda, Tamara R
AU - Datta, Rakesh
AU - Dong, Jesse Z
AU - Culler, Michael D
AU - Sleeman, Mark W
AU - Alvarez, Clara V
AU - Gallego, Rosalia
AU - Lelliott, Christopher J
AU - Carling, David
AU - Tschop, Matthias H
AU - Dieguez, Carlos
AU - Vidal-Puig, Antonio
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18460330
U2 - 10.1016/j.cmet.2008.03.006
DO - 10.1016/j.cmet.2008.03.006
M3 - Article
SN - 1550-4131
VL - 7
SP - 389
EP - 399
JO - Cell Metabolism
JF - Cell Metabolism
IS - 5
ER -