EC number 2.3.1.20 IntEnz IntEnz view ExPASy NiceZyme view | CAS number 9029-98-5 BRENDA BRENDA entry KEGG KEGG entry | |
Diglyceride acyltransferase (or O-acyltransferase), DGAT, catalyzes the formation of triglycerides from diacylglycerol and Acyl-CoA. The reaction catalyzed by DGAT is considered the terminal and only committed step in triglyceride synthesis and to be essential for the formation of adipose tissue. The protein is homologous to other membrane-bound O-acyltransferases.
Contents
Isoforms
There are two isozymes 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 and a number of DGAT-1 inhibitors are in clinical trials for this indication.