Humanized monoacylglycerol acyltransferase 2 mice develop metabolic dysfunction-associated steatohepatitis.

ABSTRACT: Mice lacking monoacylglycerol acyltransferase 2 (mMGAT2¹) are resistant to diet-induced fatty liver, suggesting hMOGAT2 inhibition is a viable option for treating metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH). We generated humanized hMOGAT2 mice (HuMgat2) for use in pre-clinical studies testing the efficacy of hMOGAT2 inhibitors for treating MASLD/MASH. HuMgat2 mice developed MASH when fed a steatotic diet. Computer-aided histology revealed the presence of hepatocyte cell ballooning, immune cell infiltration, and fibrosis. Hepatocytes accumulated Mallory-Denk bodies containing phosphorylated p62/sequestosome-1-ubiquitinated protein aggregates likely caused by defects in autophagy. Metainflammation and apo

SUBMITTER: Corbalan JJ 

PROVIDER: S-EPMC11648239 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature