Regulation of lipid‐induced macrophage polarization through modulating peroxisome proliferator‐activated receptor‐gamma activity affects hepatic lipid metabolism via a Toll‐like receptor 4/NF‐κB signaling pathway

• DOI: 10.1111/jgh.15025
• Publication Date: 2020-03-04T01:25:43Z
• Authors: Hui‐Min Wu; Xi‐Xi Ni; Qin‐Yu Xu; Qi Wang; Xiao‐Yun Li; Jing Hua
• Keywords: Macrophage polarization; Steatosis

Abstract Background and Aim Chronic inflammation links closely to insulin resistance lipid metabolism in nonalcoholic fatty liver disease (NAFLD). Macrophage M1 activation plays an important role the initiation continuing of pro‐inflammatory response NAFLD. Our study was investigate whether macrophage M1/M2 polarization switching would affect hepatic through modulation peroxisome proliferator‐activated receptor‐gamma (PPAR‐γ) activity vivo vitro . Methods RAW264.7 macrophages were treated with different acids, cell culture supernatants collected prepare conditioned media (CM). Different co‐culture systems between primary hepatocytes CM from established. A PPAR‐γ agonist or antagonist administered regulate polarization. phenotype markers, inflammatory signaling pathway, lipid‐related genes expression determined. Wild‐type C57BL/6 mice fed a high‐fat diet induce NAFLD given rosiglitazone Results Saturated acids induced M1‐polarized while polyunsaturated M2‐polarized macrophages. significantly promoted synthesis accumulation upregulation toll‐like receptor 4 (TLR4)/NF‐κB pathway. The made lipid‐induced switch M2‐predominant phenotype, had opposite effect. shifting subsequently affected hepatocytes. Administration improved steatosis reducing TLR4/NF‐κB Kupffer cells. Conclusions Lipid‐induced metabolism. Modulation could shift Upregulation pathway is linked dysregulated