title: Signals from intra-abdominal fat modulate insulin and leptin sensitivity through different mechanisms: neuronal involvement in food-intake regulation.
abstract: Intra-abdominal fat accumulation is involved in development of the metabolic syndrome, which is associated with insulin and leptin resistance. We show here that ectopic expression of very low levels of uncoupling protein 1 (UCP1) in epididymal fat (Epi) reverses both insulin and leptin resistance. UCP1 expression in Epi improved glucose tolerance and decreased food intake in both diet-induced and genetically obese mouse models. In contrast, UCP1 expression in Epi of leptin-receptor mutant mice did not alter food intake, though it significantly decreased blood glucose and insulin levels. Thus, hypophagia induction requires a leptin signal, while the improved insulin sensitivity appears to be leptin independent. In wild-type mice, local-nerve dissection in the epididymis or pharmacological afferent blockade blunted the decrease in food intake, suggesting that afferent-nerve signals from intra-abdominal fat tissue regulate food intake by modulating hypothalamic leptin sensitivity. These novel signals are potential therapeutic targets for the metabolic syndrome.
authors.affiliation: Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamada
authors.forename: Hideki
authors.initials: H
authors.lastname: Katagiri
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishigaki
authors.forename: Takehide
authors.initials: T
authors.lastname: Ogihara
authors.forename: Junta
authors.initials: J
authors.lastname: Imai
authors.forename: Kenji
authors.initials: K
authors.lastname: Uno
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Junhong
authors.initials: J
authors.lastname: Gao
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Ishihara
authors.forename: Akira
authors.initials: A
authors.lastname: Niijima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Oka
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004822:Epididymis / Q000166:cytology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D007473:Ion Channels; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D000071256:Uncoupling Protein 1
chemical_list: D002352:Carrier Proteins; D007328:Insulin; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D005947:Glucose