DGAT2

DGAT2 (diacylglycerol O-acyltransferase 2) catalyzes the terminal and committed step of triacylglycerol (TG) synthesis by esterifying diacylglycerol with fatty acyl-CoA, thereby regulating intracellular lipid storage and lipid droplet formation^[1][2]. DGAT2 is predominantly expressed in liver, adipose tissue, mammary gland, testis, peripheral leukocytes, and cardiac tissue, where it supports TG synthesis and intracellular lipid accumulation^[3]. Mechanistically, DGAT2 functions within fatty acid metabolism pathways that maintain cellular energy balance, and its activity contributes directly to lipid droplet biogenesis through TG production^[2][3]. In metabolic disease models, suppression of DGAT2 reduces hepatic diacylglycerol and triglyceride levels and improves insulin sensitivity, supporting its role in hepatic lipid homeostasis and metabolic regulation^[4]. DGAT2 inhibition in hepatocytes also blocks SREBP-1 cleavage and lowers liver triglyceride accumulation, further linking DGAT2 activity to hepatic lipid metabolic pathways^[5]. Compared with the related isoform DGAT1, DGAT2 displays distinct tissue distribution, intracellular localization, and physiological functions despite catalyzing the same biochemical reaction^[2][3]. DGAT2 can localize to lipid droplets and is strongly associated with intracellular lipid storage, whereas DGAT1 is primarily retained within the endoplasmic reticulum and contributes preferentially to dietary fat processing and fatty acid utilization pathways^[3]. Therefore, DGAT2-selective inhibitors, including clinical-stage compounds such as ervogastat, have been developed to reduce liver fat content and investigate therapeutic strategies targeting metabolic dysfunction-associated steatotic liver disease and related disorders^[5][6].