Angiogenesis Inhibitor ZM 306416 Reduces Non-Alcoholic Fatty Liver Disease in Mice Induced by High-Fat Diet

Abstract

Nonalcoholic fatty liver disease (NAFLD) causes countless burden to people worldwide, especially when the quality of people’s life is improved constantly. It has clinical significance to find novel methods to deal with this common disease. Here, we aimed to assess whether angiogenesis inhibitor ZM306416 could improve NAFLD. Mice were fed with different diets for 15 weeks and treated with ZM306416 followed by analysis of weight and inflammatory infiltration of adipose tissue, fatty degeneration, and fibrosis by immunohistochemistry, fibrosis-related proteins level by qRT-PCR. Compared to control group, ZM306416 treatment significantly declined mice weight and adipose tissue weight. In addition, ZM306416 decreased blood vessel density of adipose tissues, mitigated inflammatory infiltration, fatty degeneration, and fibrosis. Moreover, ZM304616 alleviated adipose fibrosis-related protein expression, and transcription of inflammatory genes and adipogenesis genes. However, the inhibitor enhanced β-oxidation of fatty acid, Nrf2, and SOD2, while decreased serum markers of liver injury. In conclsuion, angiogenesis inhibitor ZM306416 attenuates adipose fibrosis and degradation, promotes adipose functions and lipid metabolism, thereby alleviating obesity-induced nonalcoholic fatty liver.