Publication Summary:

The growing global incidence of NASH mirrors the availability of nutrients. Over-nutrition also results in insulin resistance and type-2 diabetes, which are often co-morbidities associated with NASH and are known to drive more adverse outcomes. MSDC-0602K, a modulator of the mitochondrial pyruvate carrier (MPC), is in clinical trials as a potential treatment for NASH. Preclinical studies have shown that the mitochondrial pyruvate carrier is increased in expression in animals fed a high fat diet. Moreover, selective knockouts of each of the mitochondrial proteins that make up the carrier have shown that the MPC is a key driver of both NASH pathology and pharmacology of MSDC-0602K. Diet-induced disease using a three-dimensional multicellular human tissue model provides the potential to reconstruct the effects of overnutrition in vitro and to potentially model the actions of an agent like MSDC-0602K.