Research ArticlePhysiology

GPRC5B Activates Obesity-Associated Inflammatory Signaling in Adipocytes

Sci. Signal.  20 Nov 2012:
Vol. 5, Issue 251, pp. ra85
DOI: 10.1126/scisignal.2003149

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Promoting Inflammation and Obesity

The gene encoding GPRC5B, an orphan G protein–coupled receptor found in the brain and adipose tissue, represents an obesity susceptibility locus in humans. Kim et al. found that, compared to their wild-type counterparts, GPRC5B-deficient mice were less obese, had reduced inflammatory signaling in their white adipose tissue, and showed decreased insulin resistance when fed a high-fat diet. In wild-type mouse embryonic fibroblasts, GPRC5B was phosphorylated by and associated with the kinase Fyn, which led to enhanced activation of proinflammatory nuclear factor κB signaling involving the kinase IKKε. GPRC5B-deficient cells expressing a mutant GPRC5B that could not interact with Fyn did not enhance inflammatory signaling. These findings should encourage investigation of a role for GPRC5B in promoting inflammation and obesity in humans.