Hepatic DDAH1 mitigates hepatic steatosis and insulin resistance in obese mice: Involvement of reduced S100A11 expression.

ABSTRACT: Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is an important regulator of plasma asymmetric dimethylarginine (ADMA) levels, which are associated with insulin resistance in patients with nonalcoholic fatty liver disease (NAFLD). To elucidate the role of hepatic DDAH1 in the pathogenesis of NAFLD, we used hepatocyte-specific Ddah1-knockout mice (Ddah1^HKO) to examine the progress of high-fat diet (HFD)-induced NAFLD. Compared to diet-matched flox/flox littermates (Ddah1^f/f), Ddah1^HKO mice exhibited higher serum ADMA levels. After HFD feeding for 16 weeks, Ddah1^HKO mice developed more severe liver steatosis and worse insulin resistance than Ddah1^f/f mice. On the contrary, overexpression of DDA

SUBMITTER: Shen X 

PROVIDER: S-EPMC10465955 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature