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Science 329 (5990): 454-457

Copyright © 2010 by the American Association for the Advancement of Science

Sfrp5 Is an Anti-Inflammatory Adipokine That Modulates Metabolic Dysfunction in Obesity

Noriyuki Ouchi,1,* Akiko Higuchi,1 Koji Ohashi,1 Yuichi Oshima,1 Noyan Gokce,2 Rei Shibata,3 Yuichi Akasaki,1 Akihiko Shimono,4 Kenneth Walsh1,*

Abstract: Adipose tissue secretes proteins referred to as adipokines, many of which promote inflammation and disrupt glucose homeostasis. Here we show that secreted frizzled-related protein 5 (Sfrp5), a protein previously linked to the Wnt signaling pathway, is an anti-inflammatory adipokine whose expression is perturbed in models of obesity and type 2 diabetes. Sfrp5-deficient mice fed a high-calorie diet developed severe glucose intolerance and hepatic steatosis, and their adipose tissue showed an accumulation of activated macrophages that was associated with activation of the c-Jun N-terminal kinase signaling pathway. Adenovirus-mediated delivery of Sfrp5 to mouse models of obesity ameliorated glucose intolerance and hepatic steatosis. Thus, in the setting of obesity, Sfrp5 secretion by adipocytes exerts salutary effects on metabolic dysfunction by controlling inflammatory cells within adipose tissue.

1 Molecular Cardiology and Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA.
2 Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, E703E, Boston, MA 02118, USA.
3 Department of Cardiology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
4 Cancer Science Institute of Singapore, National University of Singapore, Centre of Life Sciences, 28 Medical Drive, no. 02-07, Singapore 117456.

* To whom correspondence should be addressed: E-mail: kxwalsh{at} (K.W.); nouchi{at} (N.O.)

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