Inhibiting hepatocyte transketolase for MASLD and MASH

Inhibiting transketolase, a metabolic enzyme of the pentose phosphate pathway, could help treat metabolic dysfunction-associated steatotic liver disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH), also known as NASH, by increasing hepatic inosine levels, which activates the PKA/CREB signaling pathway to promote mitochondrial lipid phosphatidylcholine synthesis, thus improving liver mitochondrial function.

Metabolomic analysis, followed by proteomic analysis, identified higher transketolase levels in liver biopsies from MASLD patients than in biopsies from healthy individuals. Transketolase mRNA and protein expression were higher in liver biopsies from MASLD patients than in biopsies from individuals without MASLD. ...