Hepatic steatosis and inflammation: Role of western diet and lipoproteins

Background: We have shown in our previous study in ApoE −/− mice that leukocyte recruitment within the liver precedes the development of steatosis. Our objective was to examine the role of fat and lipoproteins in the development of non‐alcoholic steatohepatitis. Methods: Wild type C57Bl/6 mice fed normal diet (WTND) or a western diet (WTWD), P‐selectin deficient mice fed western diet and LDLr deficient mice fed normal diet (LDLND) were studied. After 8 weeks, leukocyte endothelial cell interactions we determined by intra‐vital microscopy of the hepatic microcirculation. Results: Mice on the western diet had a significantly greater weight gain (217% vs. 154%). Only WTWD mice had leukocyte recruitment in the hepatic microcirculation with significantly greater number of rolling (7.0±0.4) and firmly adherent leukocytes (5.6±0.4) within the post‐sinusoidal venules. There was no sinusoidal leukocyte recruitment in any of the groups. Mice on the western diet also had a significant reduction in the number of flowing sinusoids compared to those fed normal diet (6.6±0.4 vs. 12.8±0.7). The microcirculation of LDLND mice was not different from WTND mice. Conclusion: Mice fed a western diet develop a LDL receptor dependent hepatic steatosis with a resultant decrease in sinusoidal density. Western diet‐induced hepatic leukocyte recruitment is P‐selectin dependent in the post‐sinusoidal venules.