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

Diacylglycerol O-acyltransferase 1 and 2 (DGAT1 and DGAT2) are membrane-bound enzymes that catalyze the final and rate-limiting step in triglyceride (triacylglycerol) biosynthesis, specifically the acylation of diacylglycerol (DAG) with acyl-CoA to form triglycerides. They have distinct but partially overlapping tissue distributions and biological functions; both are required for normal triglyceride synthesis and energy storage. DGAT1 is known to play a more significant role in metabolizing dietary/exogenous fatty acids, whereas DGAT2 is more involved with endogenous fatty acid metabolism and is critical for survival, as global DGAT2 knockout is lethal. Both enzymes are considered therapeutic targets for metabolic diseases such as obesity, diabetes, and non-alcoholic fatty liver disease, and several pharmacological inhibitors are in preclinical and clinical development. Disruption of DGAT1 or DGAT2 activity profoundly impacts cellular triglyceride levels and lipid homeostasis, with downstream effects on energy metabolism and disease risk.

Other names

Diacylglycerol acyltransferase 1 (DGAT1)Diacylglycerol acyltransferase 2 (DGAT2)Acyl-CoA:diacylglycerol acyltransferase 1/2DGAT isoform 1/2EC 2.3.1.20 (enzyme classification number)

Inhibition of triglyceride synthesis by blocking acyl-CoA conjugation to diacylglycerol Reduction of lipid accumulation in tissues by decreasing triglyceride biosynthesis Alteration of fatty acid partitioning toward oxidation