iPSC-Derived Hepatocytes from Patients with MASLD Exhibit Early Mitochondrial Dysfunction

Mitochondrial mass and function were assessed under basal culture conditions and following short-term exposure to exogenous palmitate. Outcomes included gene expression, mitochondrial oxygen consumption, ROS production and cellular energy status. iPSC-Heps from MASLD patients exhibited mitochondrial alterations characteristic of their diseased origin.

The degree of mitochondrial dysfunction seen in MASLD iPSC-Heps was reminiscent of that described clinically in early MASLD, prior to progression to steatohepatitis. Mitochondrial alterations in MASLD iPSC-Heps occurred independently of PNPLA3 genotype.