1829-P: Aggravating Liver Lipid Accumulation and Fibrosis in Nonalcoholic Steatohepatitis Model of MS-NASH Mice by a Modified Amylin Diet

Abstract

MS-NASH mouse is a leptin pathway intact model of spontaneous metabolic diseases. Our previous work developed a nonalcoholic steatohepatitis (NASH) model in MS-NASH mice fed with western diet and fructose drinking water (WDF). This study showed aggravated liver cholesterol content and fibrosis score by using a modified Amylin diet (GAN). Liver Cholesterol was increased from 10.11±1.58 mg/g to 14.07±0.81 mg/g and fibrosis score increased from 1.5±0.3 to 2.1±0.2 when comparing GAN with WDF and with C57Bl/6 mice. Administration of 30 mg/kg Obeticholic Acid (OCA, QD, PO) or 30 mg/kg Elafibranor (GFT-505, QD, PO) for 8 weeks significantly reduced serum liver enzymes, liver lipids and fibrosis scores. Conclusion: The GAN diet fed MS-NASH mice can be a better NASH model for novel compound efficacy. Disclosure G. Zhang: None. K. Chng: None. Y. Wang: None.