Title:Glycerolipid Acyltransferases in Triglyceride Metabolism and Energy Homeostasis-Potential as Drug Targets
Volume: 12
Issue: 2
Author(s): Guoqing Cao, Robert J. Konrad, Shuyu D. Li and Craig Hammond
Affiliation:
Keywords:
Acyltransferase, diacylglycerol, DGAT, GPAT, metabolism, MGAT, glycerolipid, triglyceride
Abstract: Glycerolipid acyltransfereases play important roles in physiological and pathophysiological processes of
triglyceride (TAG) metabolism and energy balance. Glycerol-3-phosphate acyltransferases (GPATs) are key enzymes in
the triglyceride biosynthetic pathway. In addition to the mitochondrial GPAT1 that was first cloned and studied, novel
microsomal enzyme isoforms have been discovered in recent years. The potential function of one of the GPATs, GPAT4,
was studied in GPAT4 deficient mice that suggested its role in TAG synthesis in multiple tissues. Monoacylglycerol and
diacylglycerol acyltransferases (MGAT2 and DGAT1) are important enzymes involved in intestinal triglyceride
absorption, and studies in recent years from knockout mice have revealed their important role in whole body energy
metabolism through changes in intestinal TAG absorption kinetics. Both MGAT2 and DGAT1 mice are resistant to dietinduced
obesity and have improved insulin sensitivity and hepatic TAG accumulation. These data suggest that these
enzymes are intimately involved in TAG metabolism and whole body energy homeostasis and that inhibition of these
enzymes may provide therapeutic benefits for metabolic disorders such as obesity, metabolic syndrome, and type 2
diabetes.
