A human pluripotent stem cell model for the analysis of metabolic dysfunction in hepatic steatosis.

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is currently the most prevalent form of liver disease worldwide. This term encompasses a spectrum of pathologies, from benign hepatic steatosis to non-alcoholic steatohepatitis, which have, to date, been challenging to model in the laboratory setting. Here, we present a human pluripotent stem cell (hPSC)-derived model of hepatic steatosis, which overcomes inherent challenges of current models and provides insights into the metabolic rewiring associated with steatosis. Following induction of macrovesicular steatosis in hepatocyte-like cells using lactate, pyruvate, and octanoate (LPO), respirometry and transcriptomic analyses revealed compromised electron transport chain activity. ¹³C isotopic tracing studies revealed enhanced TCA cycle an

SUBMITTER: Sinton MC 

PROVIDER: S-EPMC7773967 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature