Abstract

stearoyl-CoA desaturase-1 (Scd1), fatty acid binding protein (Fabp) and carnitine palmitoyltransferase-1 (Cpt1) was determined with qRT-PCR. Results: Serum levels of AST and ALT were significantly higher in MCD fed mice treated with anti-VEGFR2 compared to MCD fed mice treated with NaCl (respectively p =0.009;p =0.007). Liver histology showed a decrease of steatosis (p < 0.001) and fewer inflammatory foci (p = 0.015) in the liver of anti-VEGFR2 treated mice in comparison to MCD fed mice treated with NaCl. There was no difference in fibrosis. Expression of endoglin in the liver of MCD fed mice treated with anti-VEGFR2 was significant decreased compared to MCD fed mice treated with NaCl (p = 0.005). To investigate the molecular mechanisms, we looked into genes involved in fatty acid metabolism. Scd1 was significantly higher in MCD fed mice treated with anti-VEGFR2 compared to MCD fed mice treated with NaCl (p < 0.001). Low Scd1 expression results in excess fat deposition in the liver. FABP and Cpt1 expression remained the same in both groups. Conclusion: Our results demonstrate that inhibition of VEGFR2 is protective against the development of steatosis and inflammation in a diet-induced mouse model for NASH. The effect of anti-VEGFR2 might be found in the fatty acid metabolism. These findings might give rise to new therapeutic options for NASH.

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