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This Article Full Text Full Text (PDF) All Versions of this Article: 297/3/R655    most recent 00223.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Google Scholar Articles by Le Foll, C. Articles by Levin, B. E. PubMed PubMed Citation Articles by Le Foll, C. Articles by Levin, B. E.

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Characteristics and mechanisms of hypothalamic neuronal fatty acid sensing

¹Neurology Service, Department of Veterans Affairs Medical Center, East Orange, New Jersey; ²Centre National de la Recherche Scientifique-University of Paris Diderot, Paris, France; and ³Department of Neurology and Neurosciences, New Jersey Medical School, Newark, New Jersey

Submitted 22 April 2009 ; accepted in final form 12 June 2009

We assessed the mechanisms by which specialized hypothalamic ventromedial nucleus (VMN) neurons utilize both glucose and long-chain fatty acids as signaling molecules to alter their activity as a potential means of regulating energy homeostasis. Fura-2 calcium (Ca²⁺) and membrane potential dye imaging, together with pharmacological agents, were used to assess the mechanisms by which oleic acid (OA) alters the activity of dissociated VMN neurons from 3- to 4-wk-old rats. OA excited up to 43% and inhibited up to 29% of all VMN neurons independently of glucose concentrations. In those neurons excited by both 2.5 mM glucose and OA, OA had a concentration-dependent effective excitatory concentration (EC₅₀) of 13.1 nM. Neurons inhibited by both 2.5 mM glucose and OA had an effective inhibitory concentration (IC₅₀) of 93 nM. At 0.5 mM glucose, OA had markedly different effects on these same neurons. Inhibition of carnitine palmitoyltransferase, reactive oxygen species formation, long-chain acetyl-CoA synthetase and ATP-sensitive K⁺ channel activity or activation of uncoupling protein 2 (UCP2) accounted for only 20% of OA's excitatory effects and 40% of its inhibitory effects. Inhibition of CD36, a fatty acid transporter that can alter cell function independently of intracellular fatty acid metabolism, reduced the effects of OA by up to 45%. Thus OA affects VMN neuronal activity through multiple pathways. In glucosensing neurons, its effects are glucose dependent. This glucose-OA interaction provides a potential mechanism whereby such "metabolic sensing" neurons can respond to differences in the metabolic states associated with fasting and feeding.

ventromedial nucleus; CD36; carnitine palmitoyltransferase I; reactive oxygen species; long-chain fatty acids; glucosensing

This article has been cited by other articles:

				C. Le Foll, B. G. Irani, C. Magnan, A. Dunn-Meynell, and B. E. Levin Effects of maternal genotype and diet on offspring glucose and fatty acid-sensing ventromedial hypothalamic nucleus neurons Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2009; 297(5): R1351 - R1357. [Abstract] [Full Text] [PDF]