The role of TREM2 in adipogenesis and obesity has not yet been defined. Here, we report that TREM2-transgenic (TG) mice were much more obese than wild-type mice after feeding with a high-fat diet (HFD), independent of the quantity of food intake. These HFD-fed TREM2 TG mice manifested adipocyte hypertrophy, glucose and insulin resistance and hepatic steatosis. The expression of adipogenic regulator genes, such as peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, fatty-acid synthase and CD36, was markedly increased in the epididymal white adipose tissue (EWAT) of the HFD-fed TG mice. In addition, the EWAT of the HFD-fed TG mice exhibited decreased Wnt10b expression and increased GSK-3β-mediated β-catenin phosphorylation. In contrast, the blockade of TREM2 signaling using TREM2-Ig resulted in the inhibition of adipocyte differentiation in vitro and a reduction in body weight in vivo by downregulating the expression of adipogenic regulators. Taken together, these results suggested that TREM2 induces obesity by promoting adipogenesis via the upregulation of adipogenic regulators in conjunction with the Wnt10b/β-catenin signaling pathway.
- Copyright © 2013 by The American Association of Immunologists, Inc.