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Oleic acid directly regulates POMC neuron excitability in the hypothalamus.

ABSTRACT: The mammalian CNS relies on a constant supply of external glucose for its undisturbed operation. However, neurons can readily switch to using fatty acids and ketones as alternative fuels. Here, we show that oleic acid (OA) excites pro-opiomelanocortin (POMC) neurons by inhibition of ATP-activated potassium (K(ATP)) channels. The involvement of K(ATP) channels is further supported by experiments in SUR1 KO animals. Inhibition of beta-oxidation using carnitine palmitoyltransferase-1 inhibitors blocks OA-induced depolarization. The depolarizing effect of OA is specific because it is not mimicked by octanoic acid. Furthermore, OA does not regulate the excitability of agouti-related peptide neurons. High-fat feeding alters POMC neuron excitability, but not its response to OA. Thus beta-oxidation in POMC neurons may mediate the appetite-suppressing (anorexigenic) effects of OA.

SUBMITTER: Jo YH

PROVIDER: S-EPMC2681442 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Oleic acid directly regulates POMC neuron excitability in the hypothalamus.

Jo Young-Hwan YH Su Ya Y Gutierrez-Juarez Roger R Chua Streamson S

Journal of neurophysiology 20090304 5

The mammalian CNS relies on a constant supply of external glucose for its undisturbed operation. However, neurons can readily switch to using fatty acids and ketones as alternative fuels. Here, we show that oleic acid (OA) excites pro-opiomelanocortin (POMC) neurons by inhibition of ATP-activated potassium (K(ATP)) channels. The involvement of K(ATP) channels is further supported by experiments in SUR1 KO animals. Inhibition of beta-oxidation using carnitine palmitoyltransferase-1 inhibitors blo ...[more]

PMID: 19261705

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