title: Characterization of neuropeptide Y (NPY) Y5 receptor-mediated obesity in mice: chronic intracerebroventricular infusion of D-Trp(34)NPY.
abstract: To clarify the role of the neuropeptide Y (NPY) Y5 receptor subtype in energy homeostasis, the effect of the intracerebroventricular infusion of a selective Y5 agonist, D-Trp(34)NPY, was investigated in C57BL/6J mice. Intracerebroventricular infusion of D-Trp(34)NPY (5 and 10 microg/d) produced hyperphagia and body weight gain, accompanied by increased adipose tissue weight, hypercholesterolemia, hyperinsulinemia, and hyperleptinemia. Oral administration of a selective Y5 antagonist at a dose of 100 mg/kg twice a day completely suppressed all of these D-Trp(34)NPY-induced changes, indicating that chronic activation of the Y5 receptor produces hyperphagia and obesity. In addition, D-Trp(34)NPY still resulted in an increase in adipose tissue weight accompanied by hyperleptinemia and hypercholesterolemia, although D-Trp(34)NPY-induced food intake was restricted by pair-feeding. Under the pair-fed condition, D-Trp(34)NPY decreased hormone-sensitive lipase activity in white adipose tissue and uncoupling protein-1 mRNA expression in brown adipose tissue. These findings indicate that Y5-mediated obesity may involve metabolic changes, such as decreased lipolysis and thermogenesis, as well as hyperphagia. Therefore, the Y5 receptor can play a key role in regulating energy homeostasis.
authors.affiliation: Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Tsukuba 300-2611, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mashiko
authors.forename: Akane
authors.initials: A
authors.lastname: Ishihara
authors.forename: Hisashi
authors.initials: H
authors.lastname: Iwaasa
authors.forename: Hideki
authors.initials: H
authors.lastname: Sano
authors.forename: Zenjun
authors.initials: Z
authors.lastname: Oda
authors.forename: Junko
authors.initials: J
authors.lastname: Ito
authors.forename: Mariko
authors.initials: M
authors.lastname: Yumoto
authors.forename: Mayumi
authors.initials: M
authors.lastname: Okawa
authors.forename: Jun
authors.initials: J
authors.lastname: Suzuki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukuroda
authors.forename: Makoto
authors.initials: M
authors.lastname: Jitsuoka
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Morin
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: MacNeil
authors.forename: Lex H T
authors.initials: LH
authors.lastname: Van der Ploeg
authors.forename: Masaki
authors.initials: M
authors.lastname: Ihara
authors.forename: Takehiro
authors.initials: T
authors.lastname: Fukami
authors.forename: Akio
authors.initials: A
authors.lastname: Kanatani
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004334:Drug Administration Schedule; D004734:Energy Metabolism; D006003:Glycogen / Q000378:metabolism; D006706:Homeostasis; D006963:Hyperphagia / Q000209:etiology; D007276:Injections, Intraventricular; D008024:Ligands; D008071:Lipoprotein Lipase / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009478:Neuropeptide Y / Q000008:administration & dosage; D009765:Obesity / Q000209:etiology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D002787:Sterol Esterase / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; C412628:D-Trp(34) neuropeptide Y; D004268:DNA-Binding Proteins; D008024:Ligands; D009478:Neuropeptide Y; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014280:Triglycerides; C100568:neuropeptide Y5 receptor; D006003:Glycogen; D002787:Sterol Esterase; D008071:Lipoprotein Lipase