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

Figure 1 Dietary lauric acid reduces cholestatic liver injury and macrophage infiltration in 14-day 3,5-diethoxycarbonyl-1,4-dihydrocollidine mouse model. A: Serum liver chemistries including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, and total bile acids were measured in Chow (n = 6), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) (n = 6), lauric acid (LA) (n = 6), and DDC/LA (n = 6) mice after 14 days of treatment. DDC feeding significantly increased biochemical markers of hepatocellular injury and cholestasis, whereas 5% dietary LA supplementation attenuated these changes; B: Representative hematoxylin and eosin-stained liver sections (200 ×; scale bar: 100 μm) from Chow, DDC, LA, and DDC/LA mice. DDC feeding induced periportal inflammation, cholestatic injury, and ductular expansion, which were reduced by LA treatment. Photomicrographs are representative of 6 mice in each group; C: Representative immunohistochemical staining and quantification of F4/80-positive macrophages (100 ×; scale bar: 200 μm) in liver sections. DDC mice exhibited marked hepatic macrophage accumulation, whereas LA supplementation significantly reduced inflammatory cell infiltration. Photomicrographs are representative of 6 mice in each group; D: Representative immunohistochemical staining and quantification of cytokeratin 19-positive bile duct epithelia (100 ×; scale bar: 200 μm). DDC feeding induced a robust ductular reaction which was attenuated in DDC/LA mice. Photomicrographs are representative of 6 mice in each group. 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. AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; DDC: 3,5-diethoxycarbonyl-1,4-dihydrocollidine; CK-19: Cytokeratin 19; HE: Hematoxylin and eosin.