Inhibition of adipocyte-macrophage interaction via CSF1-CSF1R by curcumin.

Adipocytes (Ad), macrophages (Mac), and lipopolysaccharide (LPS) in the adipose tissue (AT) of individuals with obesity may jointly contribute to obesity-induced pathogenesis. This study aims to examine the roles of adipocyte-macrophage interaction (AMI) and LPS in obesity-induced pathogenesis, as well as the effects of curcumin (Cur) on these interactions. An indirect co-culture model using conditioned media (CM) from 3T3-L1 Ad and J774A.1 Mac, with LPS, was used. AMI in AT and its association with systemic insulin resistance (IR) were further evaluated in a high-fat diet (HFD)-induced obese mouse model. Colony-stimulating factor 1 (CSF1), produced by Ad and Mac, additively enhanced LPS-induced Mac chemotaxis. Compared with LPS, CM from Mac and Ad differentially influenced inflammatory cytokine secretion by the other cell type, with some cytokines markedly increased by CM prepared with LPS. Furthermore, in Ad, LPS and Mac-derived CM reduced glucose transporter 4 (GLUT4) expression, with a greater reduction observed when combined. Cur inhibited some AMI-induced inflammation but did not restore AMI-repressed GLUT4 expression. Cur specifically suppressed CSF1 secretion in both cell types and inhibited colony-stimulating factor receptor (CSF1R) activation in Mac, thereby preventing AMI. AT from HFD-induced obese mice exhibited increased CSF1R and signal transducer and activator of transcription 3 activation but reduced perilipin 1 expression at AMI sites. These obese mice also showed IR and elevated inflammatory cytokine expression in AT, which Cur attenuated regardless of whether it was administered before or after obesity induction. Cur may inhibit obesity-induced inflammation and IR by preventing AMI.