The regulation of energy metabolism by the central nervous system during endurance exercise was examined. We conducted respiratory gas analysis by functionally paralyzing the ventromedial hypothalamus (VMH), the lateral hypothalamic area, and the paraventricular nucleus of the hypothalamus with local anaesthetic (lidocaine) during treadmill running at a velocity that allowed for efficient fatty acid oxidation. Our results showed that only the lidocaine treatment of the VMH attenuated fatty acid oxidation during endurance exercise. The monoaminergic neural activities at these nuclei during in vivo microdialysis in rats under the same conditions indicated a significant increase in the extracellular concentration of noradrenaline in all nuclei. Similarly, a significant increase in dopamine occurred at some points during exercise, but no change in serotonin concentration occurred regardless of exercise. Disruption of noradrenergic projections to the VMH by 6-hydroxydopamine attenuated the enhancement of fat oxidation during running. Blocker treatments clarified that noradrenergic inputs to the VMH are mediated by beta-adrenoceptors. These data indicate that information about peripheral tissues status is transmitted via noradrenergic projections originating in the medulla oblongata, which may be an important contribution by the VMH and its downstream mechanisms to enhanced fatty acid oxidation during exercise. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.