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Science 307 (5708): 426-430

Copyright © 2005 by the American Association for the Advancement of Science

Visfatin: A Protein Secreted by Visceral Fat That Mimics the Effects of Insulin

Atsunori Fukuhara,1,2* Morihiro Matsuda,1* Masako Nishizawa,3* Katsumori Segawa,1 Masaki Tanaka,1 Kae Kishimoto,3 Yasushi Matsuki,3 Mirei Murakami,4 Tomoko Ichisaka,4 Hiroko Murakami,3 Eijiro Watanabe,3 Toshiyuki Takagi,1 Megumi Akiyoshi,3 Tsuguteru Ohtsubo,3 Shinji Kihara,5 Shizuya Yamashita,5 Makoto Makishima,1 Tohru Funahashi,5 Shinya Yamanaka,4 Ryuji Hiramatsu,3 Yuji Matsuzawa,6 Iichiro Shimomura1,5,7{dagger}

Abstract: Fat tissue produces a variety of secreted proteins (adipocytokines) with important roles in metabolism. We isolated a newly identified adipocytokine, visfatin, that is highly enriched in the visceral fat of both humans and mice and whose expression level in plasma increases during the development of obesity. Visfatin corresponds to a protein identified previously as pre–B cell colony-enhancing factor (PBEF), a 52-kilodalton cytokine expressed in lymphocytes. Visfatin exerted insulin-mimetic effects in cultured cells and lowered plasma glucose levels in mice. Mice heterozygous for a targeted mutation in the visfatin gene had modestly higher levels of plasma glucose relative to wild-type littermates. Surprisingly, visfatin binds to and activates the insulin receptor. Further study of visfatin's physiological role may lead to new insights into glucose homeostasis and/or new therapies for metabolic disorders such as diabetes.

1 Department of Medicine and Pathophysiology, Graduate School of Medicine, and Department of Organismal Biosystems, Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
2 Japan Society for the Promotion of Science, Ichibancho, Chiyoda-ku, Tokyo 102-8471, Japan.
3 Genomic Science Laboratories, Sumitomo Pharmaceuticals Co. Ltd., 2-1, Takatsukasa 4-Chome, Takarazuka, Hyogo 665-0051, Japan.
4 CREST, JST, Laboratory of Animal Molecular Technology, Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
5 Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
6 Sumitomo Hospital, 5-3-20 Nakanoshima, Kita-Ku, Osaka, 530-0005, Japan.
7 PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: ichi{at}imed2.med.osaka-u.ac.jp

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