Neutrophil-Derived Myeloperoxidase Aggravates Non-Alcoholic Steatohepatitis in Low-Density Lipoprotein Receptor-Deficient Mice
Figure 4
Decreased cholesterol accumulation in the liver of LDLR−/−/MPO−/−tp mice.
A) Representative Oil red O stainings of liver sections of LDLR−/−/MPO−/−tp and LDLR−/−/MPO+/+tp mice fed a high-fat diet for 8 weeks, showing comparable lipid accumulation (100× magnification). B) Similar hepatic triglyceride levels in LDLR−/−/MPO−/−tp and LDLR−/−/MPO+/+tp mice after high-fat feeding (0.31±0.02 vs. 0.35±0.02 µg/µg protein, p = 0.24). Chow-fed LDLR−/−/MPO+/+ mice show a lower level of liver triglycerides. C) Plasma triglyceride levels are similar in LDLR−/−/MPO−/−tp and LDLR−/−/MPO+/+tp animals after high-fat feeding (1.50±0.09 vs. 1.64±0.09 mmol/l, p = 0.42). D) High-fat feeding results in higher plasma cholesterol levels in LDLR−/−/MPO+/+tp animals as compared with LDLR−/−/MPO−/−tp mice (33.5±0.1 vs. 39.5±2.0 mmol/l, p = 0.02). E) Diet-induced liver cholesterol accumulation is reduced in LDLR−/−/MPO−/−tp mice compared with LDLR−/−/MPO+/+tp animals (0.072±0.004 vs. 0.090±0.004 µg/µg protein, p = 0.01), but does not reach the level observed in chow-fed LDLR−/−/MPO+/+ mice. F) Hepatic mRNA expression of key enzymes in cholesterol metabolism is not altered in LDLR−/−/MPO−/−tp mice, whereas scavenger receptor expression is reduced (SR-B1 1.7-fold, p<0.01; CD36 1.4-fold, p<0.01, SR-A 1.2-fold, p = 0.63).