Inflammatory changes in adipose tissue enhance expression of GPR84, a medium‐chain fatty acid receptor

Abstract

a b s t r a c tIn 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 TNFa remarkably enhanced GPR84 expression. In the presence of TNFa, MCFAs down-regulated adiponectin mRNA expression in 3T3-L1 adipocytes. Taken together, our results suggest that GPR84 emerges in adipocytes in response to TNFa from infiltrating macrophages and exacerbates the vicious cycle between adiposity and diabesity.

Medium-chain Fatty Acid-sensing Receptor, GPR84, Is a Proinflammatory Receptor

“…Neutrophils are also observed to be infiltrated in adipose tissue and may have a role in the initiating event(s) of the inflammatory cascade (40). Nagasaki et al (41) recently reported that high fat diet-fed mice up-regulated GPR84 expression in adipose tissue. TNF␣-treated 3T3-L1 adipocytes remarkably enhanced GPR84 expression, and MCFAs down-regulated adiponectin mRNA expression.…”

GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis

“…Its ligands are medium-chain free fatty acids (FFAs), and it functions obviously as a lipid/ FFA sensor (35). It was suggested that GPR84 acts as a proinflammatory receptor linking fatty acid metabolism to immunological res ponses (34)(35)(36). Other fatty acids such as arachidonic acid and saturated fatty acids have been demonstrated to increase proinflammatory IL-8 along with numerous other inflammatory factors, including IL-6, TNF-α, IL-1β and CXCL1 (37).…”

Discovery and Characterization of a Novel Small-Molecule Agonist for Medium-Chain Free Fatty Acid Receptor G Protein-Coupled Receptor 84

“…In animal models of endotoxemia and multiple sclerosis (experimental autoimmune encephalomyelitis), GPR84 is upregulated in microglia, suggesting that GPR84 may regulate the processes of neural inflammation (Bouchard et al, 2007). GPR84 has also been shown to emerge in adipocytes in response to tumor necrosis factor a secreted by the infiltrating macrophages, and activation of this receptor by MCFAs enhances the inhibitory effect of tumor necrosis factor a on adiponectin expression in adipocytes, suggesting that GPR84 may exacerbate obesity-associated insulin resistance (Nagasaki et al, 2012). It has also been demonstrated that GPR84 in zebrafish is involved in the accumulation of intracellular lipid droplets, and undecanoic acid can enhance LPS-induced IL-12 p40 production through GPR84 in zebrafish, indicating that GPR84 is a direct factor bridging fatty acid metabolism and immunologic regulation (Huang et al, 2014).…”