Lauric acid attenuates 14-day DDC-induced cholangiopathy in association with reduced NF-κB-CCL2 signaling and restored LRH-1-regulated gene expression

Figure 3 Dietary lauric acid downregulates hepatic fibrosis, and alters macrophage-associated transcriptional markers in 3,5-diethoxycarbonyl-1,4-dihydrocollidine mice. A: Representative Picrosirius red staining of liver sections from Chow, 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), lauric acid (LA), and DDC/LA mice following 14 days of treatment. DDC feeding induced periportal collagen deposition that was prevented by dietary LA supplementation; B: Quantification of Picrosirius red-positive (100 ×) staining area in liver sections (n = 4 mice per group) mice; C: Relative hepatic mRNA expression of fibrosis-associated genes Adam1, Col1a1, Spp1, Mmp13, and Timp2. DDC increased the expression of profibrotic and matrix-remodeling genes, whereas dietary LA reduced their expression (except Timp2). Groups included 5 Chow, 5 DDC, 4 LA, and 4 DDC/LA mice; D: Relative mRNA expression of pro-inflammatory genes Ccl2, Itgam, Cxcl2, and Cd68 in isolated intrahepatic mononuclear cells. DDC feeding induced inflammatory immune activation, which was attenuated by dietary LA treatment. Mice included Chow (n = 5-6), DDC (n = 5), LA (n = 4), and DDC/LA (n = 4); E: Relative mRNA expression of anti-inflammatory macrophage markers Retnlg, Chil3, Arg1, and Clec10a1 in isolated intrahepatic mononuclear cells showing upregulation in DDC/LA mice compared to DDC mice. Data are presented as mean ± SEM. Statistical significance was determined by one-way analysis of variance with Tukey’s multiple-comparison test. ^aP < 0.05 vs all groups; ^bP < 0.05 vs 3,5-diethoxycarbonyl-1,4-dihydrocollidine. DDC: 3,5-diethoxycarbonyl-1,4-dihydrocollidine; IHMC: Intrahepatic mononuclear cells.