Portal de Periódicos da CAPES

Hypothalamic Fatty Acid Metabolism Mediates the Orexigenic Action of Ghrelin

2008; Cell Press; Volume: 7; Issue: 5 Linguagem: Inglês

10.1016/j.cmet.2008.03.006

1932-7420

Miguel López, Ricardo Lage, Asish K. Saha, Diego Pérez–Tilve, María J. Vázquez, Luis Varela, Susana Sangiao‐Alvarellos, Sulay Tovar, Kawtar Raghay, Sergio Rodrı́guez-Cuenca, Rosangela M. Deoliveira, Tamara R. Castañeda, Rakesh Datta, Jesse Z. Dong, Michael D. Culler, Mark W. Sleeman, Clara V. Álvarez, Rosalı́a Gallego, Christopher J. Lelliott, David Carling, Matthias H. Tschöp, Carlos Diéguez, António Vidal-Puig,

Sleep and Wakefulness Research

Summary 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.