Diacylglycerol O-acyltransferase (DGAT)

The triglyceride synthesis machinery, primarily represented by the enzyme Diacylglycerol O-acyltransferase (DGAT), is responsible for the final and rate-limiting step in the formation of triglycerides from diacylglycerol and acyl-CoA. This enzymatic process is critical for the assembly and secretion of very-low-density lipoproteins (VLDL) in the liver and chylomicrons in the intestines. Omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are potent therapeutic modulators of this machinery used to treat severe hypertriglyceridemia. They act by inhibiting the activity of DGAT and phosphatidate phosphohydrolase while simultaneously promoting fatty acid beta-oxidation and suppressing de novo lipogenesis via SREBP-1c inhibition. By reducing the availability of fatty acid substrates and the activity of the synthesis enzymes, these agents effectively lower circulating triglyceride levels and are utilized to reduce the risk of major adverse cardiovascular events.

Other names

Triglyceride synthesis machineryAcyl-CoA:1,2-diacylglycerol acyltransferaseTAG synthesis machineryDiglyceride acyltransferase

Inhibition of Diacylglycerol O-acyltransferase (DGAT) and phosphatidate phosphohydrolase, leading to decreased hepatic triglyceride synthesis and reduced secretion of very-low-density lipoproteins (VLDL).