Diacylglycerol O-acyltransferase 2 (DGAT2) (DGAT2)

The liver enzymes involved in triglyceride synthesis represent a group of metabolic proteins responsible for the hepatic assembly of neutral lipids, with Diacylglycerol O-acyltransferase 2 (DGAT2) serving as the primary terminal therapeutic target (UniProt Q96PD7). These enzymes catalyze the sequential acylation of a glycerol-3-phosphate backbone to form triacylglycerols, which are subsequently stored in hepatic lipid droplets or exported into the bloodstream as very-low-density lipoproteins (VLDL) [1, 5]. In pathological conditions such as non-alcoholic steatohepatitis (NASH), now commonly referred to as MASH, overactivity in this pathway results in excessive hepatic steatosis, driving lipotoxicity, inflammation, and progressive fibrosis [1, 2]. Pharmaceutical agents like the DGAT2 inhibitor ervogastat and the antisense oligonucleotide Ionis-DGAT2-L_Rx are designed to reduce liver fat by specifically blocking the terminal step of lipid assembly [5]. In drug development, these inhibitors are frequently studied in combination with upstream modulators like Acetyl-CoA carboxylase (ACC) inhibitors to maximize reduction in liver fat while counteracting metabolic feedback loops that could otherwise elevate systemic triglyceride levels [1, 5].

Other names

Liver enzymes involved in triglyceride synthesisAcyl-CoA:diacylglycerol acyltransferase 2Triglyceride synthaseHepatic triglyceride synthesis enzymesDGAT2

Inhibition of enzymes that catalyze the final or rate-limiting steps of triglyceride assembly to reduce hepatic fat accumulation and VLDL secretion.