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Published Online December 16, 2004
Science DOI: 10.1126/science.1097243

Reports

This article has been retracted

Submitted on February 26, 2004
Accepted on October 29, 2004

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

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

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; Japan Society for the Promotion of Science, Ichibancho, Chiyoda-ku, Tokyo 102-8471, Japan.
2 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.
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 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; Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.

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

Fat tissue produces a variety of secreted proteins (adipocytokines) with important roles in metabolism. Here we isolate a new 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 plasma glucose levels compared with 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 like diabetes.


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