Humanized monoacylglycerol acyltransferase 2 mice on a high-fat diet exhibit impaired liver detoxification during metabolic dysfunction-associated steatotic liver disease.

ABSTRACT: Obesity significantly increases the risk of hyperlipidemia, type 2 diabetes, and liver disease. This study examined humanized monoacylglycerol acyltransferase 2 mice (HuMgat2) and their response to a high fat diet (HFD) while investigating hepatocyte dysfunction during obesity development. HuMgat2 mice fed a HFD exhibited hyperlipidemia, hyperglycemia, insulin resistance, and metabolic dysfunction-associated steatotic liver disease (MASLD). Elevated levels of cholesterol and triglycerides were associated with increased expression of lipogenic genes and accumulation of nuclear Srebp1/Srebp2. Mice fed a HFD demonstrated impaired insulin signaling and increased glucose production through the expression of gluconeogenesis genes. Liver fibrosis was characterized by collagen deposition and activ

SUBMITTER: Corbalan JJ 

PROVIDER: S-EPMC12527207 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature