Diacylglycerol O-acyltransferase (DGAT) (DGAT)

Diacylglycerol O-acyltransferase (DGAT) is a critical enzyme that catalyzes the final and only committed step in the synthesis of triglycerides by joining diacylglycerol and fatty acyl-CoA [1.2.2, 1.3.2]. There are two primary isoforms, DGAT1 and DGAT2, which belong to different gene families and exhibit distinct tissue distributions and physiological roles [1.1.2, 1.4.1]. DGAT1 is highly expressed in the small intestine and is essential for the absorption of dietary fats, while DGAT2 is predominantly found in the liver and is closely linked to hepatic triglyceride synthesis and VLDL secretion [1.1.1, 1.2.4]. Due to their central role in lipid metabolism, DGAT enzymes are major therapeutic targets for metabolic disorders such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD) [1.1.3, 1.2.1]. Pharmacological inhibition of DGAT1 has been shown to reduce postprandial triglycerides and body weight, though its clinical utility is often limited by gastrointestinal side effects like diarrhea [1.1.5, 1.2.3]. In contrast, DGAT2 inhibitors like Ervogastat are being actively developed for the treatment of non-alcoholic steatohepatitis (NASH) due to their ability to significantly reduce liver fat content with a more favorable safety profile [1.1.2, 1.4.2]. Emerging research also suggests a potential role for DGAT inhibition in cancer therapy by disrupting lipid droplet formation in tumor cells [1.4.1, 1.4.2].

Other names

Diglyceride acyltransferaseAcyl-CoA:diacylglycerol acyltransferaseDGAT1DGAT2Diacylglycerol acyltransferase 1Diacylglycerol acyltransferase 2

Inhibition of DGAT1 or DGAT2 enzymes to block the final step of triglyceride synthesis, thereby reducing lipid accumulation in tissues and secretion into the bloodstream.