title: Modest overexpression of neuropeptide Y in the brain leads to obesity after high-sucrose feeding.
abstract: Neuropeptide Y (NPY), one of the most abundant peptide transmitters in the mammalian brain, is assumed to play an important role in feeding and body weight regulation. However, there is little genetic evidence that overexpression or knockout of the NPY gene leads to altered body weight regulation. Previously, we developed NPY-overexpressing mice by using the Thy-1 promoter, which restricts NPY expression strictly within neurons in the central nervous system, but we failed to observe the obese phenotype in the heterozygote. Here we report that in the homozygous mice, overexpression of NPY leads to an obese phenotype, but only after appropriate dietary exposure. NPY-overexpressing mice exhibited significantly increased body weight gain with transiently increased food intake after 50% sucrose--loaded diet, and later they developed hyperglycemia and hyperinsulinemia without altered glucose excursion during 1 year of our observation period.
authors.affiliation: Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kaga
authors.forename: A
authors.initials: A
authors.lastname: Inui
authors.forename: M
authors.initials: M
authors.lastname: Okita
authors.forename: A
authors.initials: A
authors.lastname: Asakawa
authors.forename: N
authors.initials: N
authors.lastname: Ueno
authors.forename: M
authors.initials: M
authors.lastname: Kasuga
authors.forename: M
authors.initials: M
authors.lastname: Fujimiya
authors.forename: N
authors.initials: N
authors.lastname: Nishimura
authors.forename: R
authors.initials: R
authors.lastname: Dobashi
authors.forename: Y
authors.initials: Y
authors.lastname: Morimoto
authors.forename: I M
authors.initials: IM
authors.lastname: Liu
authors.forename: J T
authors.initials: JT
authors.lastname: Cheng
mesh_terms: D000375:Aging; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001921:Brain / Q000502:physiology*; D003510:Cyclohexanes / Q000494:pharmacology; D019422:Dietary Sucrose / Q000494:pharmacology*; D002149:Energy Intake / Q000187:drug effects; D006720:Homozygote; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009478:Neuropeptide Y / Q000235:genetics / Q000502:physiology*; D009765:Obesity / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors; D012016:Reference Values; D018800:Thy-1 Antigens / Q000235:genetics; D014966:Xanthenes / Q000494:pharmacology
chemical_list: D003510:Cyclohexanes; D019422:Dietary Sucrose; C410588:L 152804; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D018800:Thy-1 Antigens; D014966:Xanthenes; D001120:Arginine; C117416:BIBO 3304