Enpp1 ameliorates MAFLD by regulating hepatocyte lipid metabolism through the AMPK/PPARα signaling pathway.

ABSTRACT:

Background

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become the leading chronic liver disease globally, and there are no approved pharmacotherapies to treat this disease. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) has been found to be related to insulin resistance and lipid accumulation. However, the role and mechanism of Enpp1 in the development of MAFLD remain unknown.

Results

Here we discovered that Enpp1 is lowly expressed in the liver of MAFLD patients by clinical investigation. Knocking out Enpp1 in the liver of mice aggravated obesity, insulin resistance and hepatic steatosis, and these effects were reversed by liver-specific Enpp1 overexpression. Through transcriptomic data mining and experimental validation, we demonstrated tha

SUBMITTER: Liu X 

PROVIDER: S-EPMC11841222 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature