Diglyceride acyltransferase (or O-acyltransferase), DGAT, catalyzes the formation of triglycerides from diacylglycerol and Acyl-CoA

Acyl-CoA

Acyl-CoA is a group of coenzymes involved in the metabolism of fatty acids. It is a temporary compound formed when coenzyme A attaches to the end of a long-chain fatty acid inside living cells. The compound undergoes beta oxidation, forming one or more molecules of acetyl-CoA...

. The reaction catalyzed by DGAT is considered the terminal and only committed step

Committed step

In enzymology, the committed step is an effectively irreversible enzymatic reaction that occurs at a branch point during the biosynthesis of some molecules.-What it means:...

 in triglyceride synthesis and to be essential for the formation of adipose tissue.

Isoforms

There are two isozyme

Isozyme

Isozymes are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. These enzymes usually display different kinetic parameters Isozymes (also known as isoenzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. These enzymes...

s of DGAT encoded by the genes DGAT1 and DGAT2. Although both isozymes catalyze similar reactions, they have no sequence homology to each other.

Knockout studies

Mice with genetic disruption of the dgat1 or dgat2 genes have been made by the Farese laboratory at UCSF. Surprisingly, DGAT1^-/- mice are healthy and fertile and have no changes in triglyceride levels. These mice are also lean and resistant to diet-induced obesity, consequently generating interest in DGAT1 inhibitors for the treatment of obesity. In contrast, DGAT2^-/- mice have reduced triglyceride levels but are lipopenic, suffer from skin barrier abnormalities (including the inability to retain moisture), and die shortly after birth.

Therapeutic application

DGAT-1 inhibitors have potential for the treatment of obesity

Obesity

Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...

 and a number of DGAT-1 inhibitors are in clinical trials for this indication.