Diacylglycerol O-acyltransferase 1 (DGAT1) and Diacylglycerol O-acyltransferase 2 (DGAT2) (DGAT1, DGAT2)

Diacylglycerol O-acyltransferases—DGAT1 and DGAT2—are key enzymes responsible for the final step in triglyceride synthesis in the liver. They catalyze the esterification of diacylglycerol with a fatty acyl-CoA to form triacylglycerols. This process occurs primarily at the endoplasmic reticulum membrane. The synthesized triglycerides are then packaged into very-low-density lipoproteins (VLDL) for secretion into circulation or stored within hepatocytes as lipid droplets. Both enzymes play critical roles in energy storage, metabolic regulation during fasting/feeding cycles, and have been implicated in diseases such as non-alcoholic fatty liver disease, obesity-related disorders, cardiovascular disease risk via dyslipidemia, and even viral pathogenesis such as hepatitis C virus replication organelle formation. Inhibition of these enzymes is being explored therapeutically but presents challenges related to systemic lipid handling and potential adverse effects on hepatic function.

Other names

Acyl-CoA:diacylglycerol acyltransferase 1Acyl-CoA:diacylglycerol acyltransferase 2Triglyceride synthaseTriacylglycerol synthase

Drugs targeting these enzymes typically act as enzyme inhibitors, blocking the final step of triglyceride synthesis by inhibiting the transfer of an acyl group from acyl-CoA to diacylglycerol, thereby reducing triglyceride production and secretion.