Cloning of DGAT2, a second mammalian diacylglycerol acyltransferase, and related family members

Studies involving the cloning and disruption of the gene for acyl-CoA:diacy lglycerol acyltransferase (DGAT) have shown that alternative mechanisms exi st for triglyceride synthesis. In this study, we cloned and characterized a second mammalian DGAT, DGAT2, which was identified by its homology to a DG AT in the fungus Mortierella rammaniana. DGAT2 is a member of a gene family that has no homology with DGAT1 and includes several mouse and human homol ogues that are candidates for additional DGAT genes. The expression of DGAT 2 in insect cells stimulated triglyceride synthesis 6-fold in assays with c ellular membranes, and DGAT2 activity was dependent on the presence of fatt y acyl-CoA and diacylglycerol, indicating that this protein is a DGAT. Acti vity was not observed for acyl acceptors other than diacylglycerol. DGAT2 a ctivity was inhibited by a high concentration (100 mM) of MgCl2 in an in vi tro assay, a characteristic that distinguishes DGAT2 from DGAT1. DGAT2 is e xpressed in many tissues with high expression levels in the liver and white adipose tissue, suggesting that it may play a significant role in mammalia n triglyceride metabolism.