Identification of a Metabolic, Transcriptomic, and Molecular Signature of Patatin-Like Phospholipase Domain Containing 3-Mediated Acceleration of Steatohepatitis.

ABSTRACT:

Background and aims

The mechanisms by which the I148M mutant variant of the patatin-like phospholipase domain-containing 3 (PNPLA3^I148M ) drives development of nonalcoholic steatohepatitis (NASH) are not known. The aim of this study was to obtain insights on mechanisms underlying PNPLA3^I148M -induced acceleration of NASH.

Approach and results

Hepatocyte-specific overexpression of empty vector (luciferase), human wild-type PNPLA3, or PNPLA3^I148M was achieved using adeno-associated virus 8 in a diet-induced mouse model of nonalcoholic fatty liver disease followed by chow diet or high-fat Western diet with ad libitum administration of sugar in drinking water (WDSW) for 8 weeks. Under WDSW, PNPLA3^I148M overexpression accelerated steato

SUBMITTER: Banini BA 

PROVIDER: S-EPMC8046714 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature