Oleic acid directly regulates POMC neuron excitability in the hypothalamus.
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.
Jo
Young-Hwan
YH
Albert Einstein College of Medicine, Department of Medicine, Division of Endocrinology, 1300 Morris Park Ave, Bronx, NY 10467, USA. yjo@aecom.yu.edu
Su
Ya
Y
Gutierrez-Juarez
Roger
R
Chua
Streamson
S
D018528:ATP-Binding Cassette Transporters; D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D003981:Diazoxide / Q000494:pharmacology; D004041:Dietary Fats / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D005947:Glucose / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007031:Hypothalamus / Q000166:cytology*; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology*; D018408:Patch-Clamp Techniques / Q000379:methods; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying / Q000172:deficiency / Q000187:drug effects / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D011955:Receptors, Drug / Q000172:deficiency; D064233:Sulfonylurea Receptors
D018528:ATP-Binding Cassette Transporters; C577508:Abcc8 protein, mouse; D004041:Dietary Fats; D007004:Hypoglycemic Agents; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D049452:Green Fluorescent Proteins; D019301:Oleic Acid; D011333:Pro-Opiomelanocortin; D000255:Adenosine Triphosphate; D005947:Glucose; D003981:Diazoxide; D005905:Glyburide