Fat’s Mixed Messages

Science Signaling  27 Jul 2010:
Vol. 3, Issue 132, pp. ec229
DOI: 10.1126/scisignal.3132ec229

Certain metabolic disorders, such as type 2 diabetes, are more prone to arise in obese individuals, a link that has been attributed, in part, to the detrimental activities of adipokines—proteins secreted by fat cells. Most adipokines disrupt glucose homeostasis by promoting inflammation and insulin resistance. Ouchi et al. (see the Perspective by Oh and Olefsky) identify a new adipokine, secreted frizzled-related protein 5 (Sfrp5), which has the opposite effect: It is anti-inflammatory and appears to promote metabolic health. In obese mice, Sfrp5 suppresses the activation of key inflammatory cells (macrophages) residing within adipose tissue by inhibiting the c-Jun N-terminal kinase (JNK) signaling pathway. Further study of this Sfrp5-JNK1 regulatory axis in fat may offer therapeutic opportunities for obesity-linked metabolic disorders.

N. Ouchi, A. Higuchi, K. Ohashi, Y. Oshima, N. Gokce, R. Shibata, Y. Akasaki, A. Shimono, K. Walsh, Sfrp5 is an anti-inflammatory adipokine that modulates metabolic dysfunction in obesity. Science 329, 454–457 (2010). [Abstract] [Full Text]

D. Y. Oh, J. M. Olefsky, Wnt fans the flames in obesity. Science 329, 397–398 (2010). [Summary] [Full Text]