Effects of Oleic Acid on Distinct Populations of Neurons in the Hypothalamic Arcuate Nucleus Are Dependent on Extracellular Glucose Levels

• Published in: Journal of neurophysiology Vol. 95; no. 3; pp. 1491 - 1498
• Main Authors: Wang, R, Cruciani-Guglielmacci, C, Migrenne, S, Magnan, C, Cotero, V. E, Routh, V. H
• Format: Journal Article
• Language: English
• Published: United States Am Phys Soc 01-03-2006; American Physiological Society
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Arcuate Nucleus of Hypothalamus - drug effects; Arcuate Nucleus of Hypothalamus - physiology; Cells, Cultured; Dose-Response Relationship, Drug; Extracellular Fluid - metabolism; Fatty Acids - metabolism; Glucose - metabolism; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; Metabolic Clearance Rate - drug effects; Nerve Net - drug effects; Nerve Net - physiology; Neurons - classification; Neurons - drug effects; Neurons - physiology; Oleic Acid - administration & dosage; Rats; Rats, Sprague-Dawley
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00697.2005

1 Department of Pharmacology and Physiology, New Jersey Medical School, Newark, New Jersey; and 2 Université Paris 7, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7059, Paris, France
Submitted 1 July 2005;
accepted in final form 17 November 2005
Pharmacological manipulation of fatty acid metabolism in the hypothalamic arcuate nucleus (ARC) alters energy balance and glucose homeostasis. Thus, we tested the hypotheses that distinctive populations of ARC neurons are oleic acid (OA) sensors that exhibit a glucose dependency, independent of whether some of these OA sensors are also glucose-sensing neurons. We used patch-clamp recordings to investigate the effects of OA on ARC neurons in brain slices from 14- to 21-day-old Sprague–Dawley (SD) rats. Additionally, we recorded spontaneous discharge rate in ARC neurons in 8-wk-old fed and fasted SD rats in vivo. Patch-clamp studies showed that in 2.5 mM glucose 12 of 94 (13%) ARC neurons were excited by 2 µM OA (OA-excited or OAE neurons), whereas six of 94 (6%) were inhibited (OA-inhibited 2.5 or OAI 2.5 neurons). In contrast, in 0.1 mM glucose, OA inhibited six of 20 (30%) ARC neurons (OAI 0.1 neurons); none was excited. None of the OAI 0.1 neurons responded to OA in 2.5 mM glucose. Thus OAI 2.5 and OAI 0.1 neurons are distinct. Similarly, in seven of 20 fed rats (35%) the overall response was OAE-like, whereas in three of 20 (15%) it was OAI-like. In contrast, in fasted rats only OAI-like response were observed (three of 15; 20%). There was minimal overlap between OA-sensing neurons and glucose-sensing neurons. In conclusion, OA regulated three distinct subpopulations of ARC neurons in a glucose-dependent fashion. These data suggest that an interaction between glucose and fatty acids regulates OA sensing in ARC neurons.
Address for reprint requests and other correspondence: V. H. Routh, Department of Pharmacology and Physiology, New Jersey Medical School, 185 S. Orange Ave, PO Box 1709, Newark, NJ 07101-1709 (E-mail: routhvh{at}umdnj.edu )