Modest Overexpression of Neuropeptide Y in the Brain Leads to Obesity After High-Sucrose Feeding
- Toshihiro Kaga1,
- Akio Inui1,
- Minoru Okita1,
- Akihiro Asakawa1,
- Naohiko Ueno1,
- Masato Kasuga1,
- Mineko Fujimiya2,
- Noriyasu Nishimura3,
- Rika Dobashi3,
- Yasuo Morimoto4,
- I-Min Liu5 and
- Juei-Tang Cheng5
- 1Second Department of Internal Medicine, Kobe University School of Medicine, Kobe
- 2Department of Anatomy, Shiga University of Medical School, Otsu
- 3Research & Development Division, Nippon Organon K.K.
- 4Kampo & Healthcare Research Laboratories, Kanebo, Osaka, Japan
- 5Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, China
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.
Footnotes
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Address correspondence and reprint requests to Akio Inui, MD, Associate Professor, Second Department of Internal Medicine, Kobe University School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. E-mail: inui{at}med.kobe-u.ac.jp.
Received for publication 16 March 2000 and accepted in revised form 16 January 2001.
AUC, area under curve; ICV, intra–third cerebroventricular; NPY, neuropeptide Y; SSC, sodium saline citrate.
