Nature Medicine
10, 1067 - 1073 (2004)
Published online: 26 September 2004; | doi:10.1038/nm1106
Neuromedin U has a novel anorexigenic effect independent of the leptin signaling pathwayReiko Hanada1, 2, Hitoshi Teranishi1, James Todd Pearson3, Mamoru Kurokawa4, Hiroshi Hosoda5, Nobuhiro Fukushima1, Yoshihiko Fukue1, Ryota Serino6, Hiroaki Fujihara6, Yoichi Ueta6, Masahito Ikawa7, Masaru Okabe7, Noboru Murakami8, Mikiyasu Shirai3, Hironobu Yoshimatsu2, Kenji Kangawa5
& Masayasu Kojima11
Molecular Genetics, Institute of Life Science, Kurume University, Kurume, Fukuoka 839-0861, Japan. 2
Department of Internal Medicine, Faculty of Medicine, Oita University, Oita 879-5593, Japan. 3
Department of Cardiac Physiology, National Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan. 4
Department of Anatomy, Nagasaki University, School of Medicine, Nagasaki 852-8523, Japan. 5
Department of Biochemistry, National Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan. 6
Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyusyu 807-8555, Japan. 7
Department of Experimental Genome Research, Genome Information Research Center, Osaka University, Yamadaoka 3-1, Suita, Osaka 565-0871, Japan. 8
Department of Veterinary Physiology, Faculty of Agriculture, Miyazaki University, Miyazaki, 889-2155, Japan.
Correspondence should be addressed to Masayasu Kojima mkojima@lsi.kurume-u.ac.jpNeuromedin U (NMU) is a hypothalamic neuropeptide that regulates body weight and composition. Here we show that mice lacking the gene encoding NMU (Nmu-/- mice) develop obesity. Nmu-/- mice showed increased body weight and adiposity, hyperphagia, and decreased locomotor activity and energy expenditure. Obese Nmu-/- mice developed hyperleptinemia, hyperinsulinemia, late-onset hyperglycemia and hyperlipidemia. Notably, however, treatment with exogenous leptin was effective in reducing body weight in obese Nmu-/- mice. In addition, central leptin administration did not affect NMU gene expression in the hypothalamus of rats. These results indicate that NMU plays an important role in the regulation of feeding behavior and energy metabolism independent of the leptin signaling pathway. These characteristic functions of NMU may provide new insight for understanding the pathophysiological basis of obesity.
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