help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mashiko, S.
Right arrow Articles by Kanatani, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mashiko, S.
Right arrow Articles by Kanatani, A.
Endocrinology Vol. 144, No. 5 1793-1801
Copyright © 2003 by The Endocrine Society

Characterization of Neuropeptide Y (NPY) Y5 Receptor-Mediated Obesity in Mice: Chronic Intracerebroventricular Infusion of D-Trp34NPY

Satoshi Mashiko, Akane Ishihara, Hisashi Iwaasa, Hideki Sano, Zenjun Oda, Junko Ito, Mariko Yumoto, Mayumi Okawa, Jun Suzuki, Takahiro Fukuroda, Makoto Jitsuoka, Nancy R. Morin, Douglas J. MacNeil, Lex H. T. Van der Ploeg, Masaki Ihara, Takehiro Fukami and Akio Kanatani

Tsukuba Research Institute (S.M., A.I., H.I., H.S., Z.O., J.I., M.Y., M.O., J.S., T.Fuku., M.J., M.I., T.Fuka., A.K.), Banyu Pharmaceutical Co., Ltd., Tsukuba 300-2611, Japan; and Merck Research Laboratories (N.R.M., D.J.M., L.H.T.V.d.P.), Merck \|[amp ]\| Co., Inc., Rahway, New Jersey 07065

Address all correspondence and requests for reprints to: Dr. Akane Ishihara, Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Okubo 3, Tsukuba 300-2611, Japan. E-mail: isihraan{at}banyu.co.jp.

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-Trp34NPY, was investigated in C57BL/6J mice. Intracerebroventricular infusion of D-Trp34NPY (5 and 10 µg/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-Trp34NPY-induced changes, indicating that chronic activation of the Y5 receptor produces hyperphagia and obesity. In addition, D-Trp34NPY still resulted in an increase in adipose tissue weight accompanied by hyperleptinemia and hypercholesterolemia, although D-Trp34NPY-induced food intake was restricted by pair-feeding. Under the pair-fed condition, D-Trp34NPY 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.




This article has been cited by other articles:


Home page
 DiabetesHome page
S. T. Ruohonen, U. Pesonen, N. Moritz, K. Kaipio, M. Roytta, M. Koulu, and E. Savontaus
Transgenic Mice Overexpressing Neuropeptide Y in Noradrenergic Neurons: A Novel Model of Increased Adiposity and Impaired Glucose Tolerance
Diabetes, June 1, 2008; 57(6): 1517 - 1525.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
J. Dark and K. M. Pelz
NPY Y1 receptor antagonist prevents NPY-induced torporlike hypothermia in cold-acclimated Siberian hamsters
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2008; 294(1): R236 - R245.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
M. M. Kamiji and A. Inui
Neuropeptide Y Receptor Selective Ligands in the Treatment of Obesity
Endocr. Rev., October 1, 2007; 28(6): 664 - 684.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
S. Mashiko, A. Ishihara, H. Iwaasa, H. Sano, J. Ito, A. Gomori, Z. Oda, R. Moriya, H. Matsushita, M. Jitsuoka, et al.
A Pair-Feeding Study Reveals That a Y5 Antagonist Causes Weight Loss in Diet-Induced Obese Mice by Modulating Food Intake and Energy Expenditure
Mol. Pharmacol., February 1, 2007; 71(2): 602 - 608.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
R. Moriya, H. Sano, T. Umeda, M. Ito, Y. Takahashi, M. Matsuda, A. Ishihara, A. Kanatani, and H. Iwaasa
RFamide Peptide QRFP43 Causes Obesity with Hyperphagia and Reduced Thermogenesis in Mice
Endocrinology, June 1, 2006; 147(6): 2916 - 2922.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Ishihara, A. Kanatani, S. Mashiko, T. Tanaka, M. Hidaka, A. Gomori, H. Iwaasa, N. Murai, S.-i. Egashira, T. Murai, et al.
A neuropeptide Y Y5 antagonist selectively ameliorates body weight gain and associated parameters in diet-induced obese mice
PNAS, May 2, 2006; 103(18): 7154 - 7158.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Mizuarai, S. Miki, H. Araki, K. Takahashi, and H. Kotani
Identification of Dicarboxylate Carrier Slc25a10 as Malate Transporter in de Novo Fatty Acid Synthesis
J. Biol. Chem., September 16, 2005; 280(37): 32434 - 32441.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Takahashi, S. Mizuarai, H. Araki, S. Mashiko, A. Ishihara, A. Kanatani, H. Itadani, and H. Kotani
Adiposity Elevates Plasma MCP-1 Levels Leading to the Increased CD11b-positive Monocytes in Mice
J. Biol. Chem., November 21, 2003; 278(47): 46654 - 46660.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2003 by The Endocrine Society