Mutations in TRIB1 have been implicated in human metabolic disorders. In Nature, Akira and colleagues show that Trib1, an adaptor protein that plays a part in protein degradation by interacting with the E3 ubiquitin ligase COP1, is critical for the differentiation of tissue-resident M2 anti-inflammatory macrophages and eosinophils, but not M1 pro-inflammatory macrophages and neutrophils, in mice. Trib1 controls myeloid cell differentiation by altering the expression of the transcription factor C/EBPα in a COP1-dependent manner. Trib1−/− mice have reduced abdominal adipose tissue when fed a normal diet and develop glucose intolerance and insulin resistance, without an increase in body weight, on a high-fat diet. Reconstitution with wild-type M2 macrophages rescues the lipodystrophy of Trib1−/− mice, suggesting that tissue-resident M2 macrophages control adipose tissue homeostasis and possibly progression to metabolic disorders.

Nature (20 March 2012) doi:10.1038/nature11930