Hepatic peroxisome proliferator-activated receptor-gamma deletion improves liver steatosis but promotes neutrophil infiltration in a high fat diet-plus-binge ethanol feeding model
Thursday, September 17, 2015 — Poster Session III
- MJ Xu
- Y Cai
- Z Zhou
- B Gao
Background and Aims: Obesity and alcohol consumption often coexist and synergistically promote steatohepatitis. However, the underlying mechanisms are still elusive. Peroxisome proliferator-activated receptor-gamma (Ppar-g) plays an important role in lipid metabolism and inflammation, the purpose of this study is to investigate its role in acute steatohepatitis induced by high-fat diet-plus-binge ethanol feeding. Methods: Hepatocyte-specific Ppar-g knockout (Ppar-gHep-/-) mice and their wild-type (WT) controls were fed with high fat diet (HFD) for 3 months, followed by binging a single dose of ethanol (HFD-plus-binge ethanol). Liver injury and inflammation were determined. Results: After HFD-plus-binge ethanol feeding, the extent of liver steatosis was markedly reduced and liver triglyceride level was lower in Ppar-gHep-/- mice than in WT mice. Sirius red staining showed that Ppar-gHep-/- mice had less degree of liver fibrosis than WT mice. Similarly, the expression of fibrosis related genes, such as Tgf-β, α-Sma and collagen genes, were much lower in Ppar-gHep-/- mice than in WT mice. However, there was no significant differences in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between Ppar-gHep-/- mice and WT mice. Compared to WT mice, myeloperoxidase (MPO) staining revealed more neutrophils infiltration in the liver of Ppar-gHep-/- mice and hepatic expression of Cxcl1 level was higher in Ppar-gHep-/- mice, which has been proved to induce liver injury by promoting neutrophil infiltration into the liver. Conclusion: Ppar-g deficiency in hepatocytes improves liver steatosis, liver fibrosis, but promotes neutrophil infiltration, which shed a new insight into the relationship between steatosis and inflammation induced by HFD-plus-binge ethanol feeding.
Category: Cell Biology