Leptin regulates interleukin-1beta expression in the brain via the STAT3-independent mechanisms.
Leptin is known to be an important circulating signal for regulation of food intake and body weight. These effects were suggested to be mediated through the hypothalamic center via the Ob-Rb receptor (long isoform of leptin receptor). Although short isoforms of leptin receptor exist in many regions of the brain, there has been little in vivo functional study of these areas such as for leptin's target site. We report here that peripherally applied leptin increased interleukin (IL)-1beta transcripts in many regions of the brain such as the hypothalamus, the hippocampus, the cortex, the cerebellum and the brainstem. Although leptin did not induce STAT3 activation or suppressor of cytokine signaling3 (SOCS3) expression in the hypothalamus of the db/db mice, which lack a functional Ob-Rb receptor, leptin increased the IL-1beta levels to similar extents as normal mice. Therefore, a novel function of leptin is suggested as the induction of IL-1beta expression in many regions of the brain via STAT3-independent mechanisms.
Hosoi
Toru
T
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo 060-0812, Japan.
Okuma
Yasunobu
Y
Nomura
Yasuyuki
Y
D000209:Acute-Phase Proteins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D007375:Interleukin-1 / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*
D000209:Acute-Phase Proteins; D004268:DNA-Binding Proteins; D007375:Interleukin-1; D020738:Leptin; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; C515447:leptin receptor, mouse