Antisense and small-molecule modulation of diacylglycerol acyltransferase

Diacylglycerol acyltransferase 1 and diacylglycerol acyltransferase 2 each catalyze the synthesis of triacylglycerol from diacylglycerol and acyl-CoA. As altered triacylglycerol metabolism is associated with a variety of human diseases, methods to modulate the activity of these enzymes have garnered considerable interest. Genetic validation for targeting the diacylglycerol acyltransferases has emerged from mouse knockout models as well as antisense oligonucleotide therapy in rodents. Small molecule inhibitors of the diacylglycerol acyltransferases, especially diacylglycerol acyltransferase 1, have been the subject of intense activity in the patent literature.