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Endocrinology Vol. 143, No. 9 3498-3504
Copyright © 2002 by The Endocrine Society

ARTICLE

Brain Stem Is a Direct Target for Leptin’s Action in the Central Nervous System

Toru Hosoi, Toru Kawagishi, Yasunobu Okuma, Jun Tanaka and Yasuyuki Nomura

Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo 060-0812, Japan

Address all correspondence and requests for reprints to: Dr. Yasunobu Okuma, Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo 060-0812, Japan. E-mail: okumay{at}pharm.hokudai.ac.jp.

Leptin is a circulating molecule for the regulation of food intake and body weight suggested to be mediated in the hypothalamus via Ob-Rb receptor, which activates Janus kinase-signal transducer and activator of transcription (STAT) pathways. Although leptin receptors exist in many regions of the brain, there have been few in vivo functional studies of leptin’s target site other than the hypothalamus. We report here that peripherally applied leptin increased STAT3 phosphorylation not only in the hypothalamus but also in the brain stem as assessed by Western blotting. Moreover, administration of leptin induced expression of the suppressor of cytokine signaling 3 mRNA, a negative feedback regulator of leptin signaling, in the brain stem as well as in the hypothalamus. Using immunohistochemistry, we observed phosphorylated STAT3-immunoreactive cells in the arcuate nucleus, ventromedial hypothalamus, lateral hypothalamic area of the hypothalamus, and the nucleus of the tractus solitarius, dorsal motor nucleus of the vagus nerve, lateral parabrachial nucleus, and central gray of the brain stem of leptin-injected mice. These findings represent physiologically functional leptin Ob-Rb receptor in the brain stem as well as in the hypothalamus. It is suggested that circulating leptin may directly act in the brain stem to elicit autonomic and neuroendocrine control of food intake and energy expenditure.




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