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

Abstract

Fat's Mixed Messages 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. (p. 454 , published online 17 June; 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.