Target intelligence / Profile preview

Acyl-CoA:diacylglycerol acyltransferase (DGAT)

Target
DGAT
Molecular classification
Enzyme, Acyltransferase
01

Overview

Acyl-CoA:diacylglycerol acyltransferase (DGAT; EC 2.3.1.20) is a key enzyme that catalyzes the final and only committed step in triacylglycerol (TAG) biosynthesis, converting diacylglycerol (DAG) and fatty acyl-CoA into TAG. This reaction is central to lipid metabolism, energy storage, and various physiological processes such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, and lactation. There are two main isoforms in eukaryotes: DGAT1 and DGAT2. DGAT activity is essential for the formation of storage lipids in cells across many organisms. Inhibition or modulation of DGAT activity has been explored for treating metabolic diseases like obesity and type 2 diabetes. Selective inhibitors like T863 or PF04620110 have been developed with high specificity for DGAT1 over DGAT2; these compounds reduce plasma triglyceride levels without significant off-target effects. Manipulation of DGAT genes is used in metabolic engineering strategies aimed at increasing oil content or modifying lipid profiles in crops or microorganisms for industrial purposes.

Other names
Diacylglycerol acyltransferaseDGAT1DGAT2Acyl-CoA--diacylglycerol acyltransferase
02

Mechanism of action

Inhibition of diacylglycerol acyltransferase activity, preventing the final step of triacylglycerol synthesis

03

Biological functions

Triacylglycerol synthesisLipid metabolismEnergy storageIntestinal fat absorptionLipoprotein assemblyAdipose tissue developmentLactation
04

Disease associations

ObesityType 2 diabetesHepatic steatosisMetabolic syndrome
05

Interacting drugs

T863

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