MGAT2

MGAT2 (monoacylglycerol acyltransferase 2) is a key enzyme in the monoacylglycerol pathway that catalyzes the conversion of monoacylglycerol and fatty acyl-CoA into diacylglycerol, thereby supporting intestinal triacylglycerol synthesis and dietary fat absorption^[1][2]. Mechanistically, MGAT2 is highly expressed in the small intestine, where it drives the re-esterification of dietary lipid intermediates and contributes to chylomicron-associated lipid transport following nutrient uptake^[1][3]. The enzyme functions upstream of diacylglycerol acyltransferases, and MGAT2-derived diacylglycerol can be utilized by DGAT2 to promote triacylglycerol synthesis, linking these enzymes within a coordinated lipid metabolic network^[4]. In metabolic disease models, enhanced flux through the MGAT pathway has been associated with obesity, insulin resistance, and nonalcoholic steatohepatitis, making MGAT2 a therapeutic target for disorders characterized by excessive triglyceride accumulation^[1][5]. Compared with related acyltransferase isoforms, MGAT2 exhibits a predominant role in intestinal lipid absorption, whereas DGAT1 and DGAT2 display distinct tissue distributions and functional specializations in triglyceride biosynthesis^[2][6]. This biological distinction has driven the development of selective MGAT2 inhibitors, which are being investigated as potential approaches to reduce triglyceride absorption while aiming to improve gastrointestinal tolerability relative to previously developed DGAT1 inhibitors^[1][7].