Characterization of neuropeptide Y (NPY) Y5 receptor-mediated obesity in mice: chronic intracerebroventricular infusion of D-Trp(34)NPY.
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.
Mashiko
Satoshi
S
Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Tsukuba 300-2611, Japan.
Ishihara
Akane
A
Iwaasa
Hisashi
H
Sano
Hideki
H
Oda
Zenjun
Z
Ito
Junko
J
Yumoto
Mariko
M
Okawa
Mayumi
M
Suzuki
Jun
J
Fukuroda
Takahiro
T
Jitsuoka
Makoto
M
Morin
Nancy R
NR
MacNeil
Douglas J
DJ
Van der Ploeg
Lex H T
LH
Ihara
Masaki
M
Fukami
Takehiro
T
Kanatani
Akio
A
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
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