Inflammatory changes in adipose tissue enhance expression of GPR84, a medium-chain fatty acid receptor: TNFα enhances GPR84 expression in adipocytes

In this study we aimed to identify the physiological roles of G protein-coupled receptor 84 (GPR84) in adipose tissue, together with medium-chain fatty acids (MCFAs), the specific ligands for GPR84. In mice, high-fat diet up-regulated GPR84 expression in fat pads. In 3T3-L1 adipocytes, co-culture with a macrophage cell line, RAW264, or TNFα remarkably enhanced GPR84 expression. In the presence of TNFα, MCFAs down-regulated adiponectin mRNA expression in 3T3-L1 adipocytes. Taken together, our results suggest that GPR84 emerges in adipocytes in response to TNFα from infiltrating macrophages and exacerbates the vicious cycle between adiposity and diabesity.

► GPR84 has been identified as a receptor for medium-chain fatty acids (MCFAs). ► GPR84 appears in white adipose tissue during the onset of obesity. ► TNFα from macrophages enhances GPR84 expression. ► MCFAs down-regulate the anti-inflammatory cytokine adiponectin through GPR84. ► MCFA–GPR84 system may contribute to promote diabesity.