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.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
López M,Lage R,Saha AK,Pérez-Tilve D,Vázquez MJ,Varela L,Sangiao-Alvarellos S,Tovar S,Raghay K,Rodríguez-Cuenca S,Deoliveira RM,Castañeda T,Datta R,Dong JZ,Culler M,Sleeman MW,Alvarez CV,Gallego R,Lelliott CJ,Carlindoi
10.1016/j.cmet.2008.03.006subject
Has Abstractpub_date
2008-05-01 00:00:00pages
389-99issue
5eissn
1550-4131issn
1932-7420pii
S1550-4131(08)00077-6journal_volume
7pub_type
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