title: Possible involvement of uncoupling protein 1 in appetite control by leptin.
abstract: Leptin reduces body fat by decreasing food intake and increasing energy expenditure. Uncoupling protein (UCP) 1, a key molecule for brown adipose tissue (BAT) thermogenesis, was reported to contribute to the stimulatory effect of leptin on energy expenditure. To clarify whether UCP1 is also involved in the anorexigenic effect of leptin, in this study we examined the effect of leptin on food intake using wild-type (WT) and UCP1-deficient (UCP1-KO) mice. Repeated injection of leptin decreased food intake more markedly in WT mice than in UCP1-KO mice, while a single injection of leptin showed similar effects in the two groups of mice. As chronic leptin stimulation induces UCP1 expression in BAT and ectopically in white adipose tissue (WAT), we mimicked the UCP1 induction by repeated injection of CL316,243 (CL), a highly specific β3-adrenoceptor agonist, and measured food intake in response to a single injection of leptin. Two-week treatment with CL enhanced the anorexigenic effect of leptin in WT mice, but not in UCP1-KO mice. Three-day treatment with CL in WT mice also enhanced the anorexigenic effect of leptin and leptin-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3) in the arcuate nucleus of the hypothalamus, without any notable change in adiposity. These results indicate that UCP1 enhances leptin action at the hypothalamus level, suggesting UCP1 contributes to the control of energy balance not only through the regulation of energy expenditure but also through appetite control by modulating leptin action.
authors: Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. keixxx@vetmed.hokudai.ac.jp
authors: Yuko
authors: Y
authors: Okamatsu-Ogura
authors: Junko
authors: J
authors: Nio-Kobayashi
authors: Toshihiko
authors: T
authors: Iwanaga
authors: Akira
authors: A
authors: Terao
authors: Kazuhiro
authors: K
authors: Kimura
authors: Masayuki
authors: M
authors: Saito
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects*; D004149:Dioxoles / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020738:Leptin / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000071256:Uncoupling Protein 1
chemical_list: D000318:Adrenergic beta-Agonists; D004149:Dioxoles; D007473:Ion Channels; D020738:Leptin; D024101:Mitochondrial Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate