Brain stem is a direct target for leptin's action in the central nervous system.
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.
Hosoi
Toru
T
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo 060-0812, Japan.
Kawagishi
Toru
T
Okuma
Yasunobu
Y
Tanaka
Jun
J
Nomura
Yasuyuki
Y
D000818:Animals; D015153:Blotting, Western; D001933:Brain Stem / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D005246:Feedback; D015870:Gene Expression / Q000187:drug effects; D007031:Hypothalamus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000032:analysis; D010766:Phosphorylation; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000032:analysis / Q000378:metabolism; D014157:Transcription Factors
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D020738:Leptin; D010750:Phosphoproteins; D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors