Fig. 1.

Deficiency in myeloid differentiation factor-2 (MD-2) and toll-like receptor 4 (TLR4), members of the lipopolysaccharide (LPS) recognition complex, protects from methionine choline-deficient (MCD) diet-induced liver injury. Mice of control genotypes and those deficient [knockout (KO)] in TLR4 (TLR4 KO) and MD-2 (MD-2 KO) were fed MCD or methionine choline-supplemented (MCS) diets for 8 wk. Liver tissue was subjected to hematoxylin and eosin (H&E) (A, left) and OilRed O (A, right) staining and F4/80 immunohistochemistry (D); one representative slide from n = 6–16 mice/group is shown. Liver triglycerides (TG) (B) and serum alanine aminotransferase (ALT) (E) levels were determined as described in materials and methods. Serum TNF-α level (F) was determined using the Multiplex assay. Liver macrophages were isolated and stained for TNF-α and the macrophage marker CD68 (ED-1) after cell permeabilization; fluorescence-activated cell sorter analysis of changes in frequency of TNF-α/CD68 double-positive cells compared with the MCS-fed genotype control is shown (C). *P < 0.05 compared with the corresponding MCS group (B, C, E, and F). #P < 0.05, MCD WT compared with MCD TLR4 KO.