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Dual Regulatory Effects of Orexins on Sympathetic Nerve Activity Innervating Brown Adipose Tissue in Rats

Department of Internal Medicine I, Faculty of Medicine, Oita University, Hasama, Oita 879-5593, Japan

Address all correspondence and requests for reprints to: Professor Hironobu Yoshimatsu, M.D., Ph.D., Department of Internal Medicine I, Faculty of Medicine, Oita University, 1–1 Idaigaoka, Hasama, Oita 879-5593, Japan. E-mail: hiroy{at}oita-med.ac.jp.

This study examined how orexin regulates the activity of the sympathetic nerves that innervate brown adipose tissue (BAT) in rats. Infusion of orexin A at a dose of 0.3 nmol into the third cerebral ventricle decreased BAT sympathetic nerve activity, compared with the effect of PBS (P < 0.05), whereas infusion of orexin B at the same dose caused a significant increase (P < 0.05). Pretreatment with a third cerebral ventricle injection of 2.24 µmol/kg -fluoromethylhistidine, an irreversible inhibitor of the histamine-synthesizing enzyme histidine decarboxylase, attenuated the orexin B-induced response of BAT sympathetic nerve activity, but not that induced by orexin A. These results indicate that orexins may regulate both BAT energy expenditure and thermogenesis through their dual effects on sympathetic nerve activity. In particular, orexin B regulates BAT sympathetic nerve activity via neuronal histamine in the hypothalamus.

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