Diacylglycerol O-Acyltransferases (DGATs), EC 188.8.131.52, are enzymes that catalyze the final step of triglyceride (TG) synthesis, the covalent attachment of fatty acyl-CoA and diacylglycerol (DAG). There have been two DGAT isoforms identified to date, DGAT1 and DGAT2, which are members of the MBOAT and DAGAT families of acyltransferases, respectively.
DGAT1/2 have a wide expression profile, being highly expressed in adipocytes, hepatocytes, enterocytes and the mammary gland, and are typically found in the endoplasmic reticulum, the site of TG synthesis. Expression of DGAT1/2 can be regulated by adipogenesis, as well as glucose and insulin levels. PPARγ and C/EBPα are thought to upregulate DGAT1/2 mRNA expression, whereas MEK-ERK signaling may suppress gene expression.
DGATs play a role in energy and glucose metabolism, as well as tissue development. Obesity is associated with an excessive accumulation of TG and DGAT inhibition has been shown to reduce weight gain in diet-induced obese mice. DGAT1 deficiency also enhances glucose metabolism in mice, while inhibition of hepatic DGAT2 has been shown to decrease insulin resistance in mice fed a high-fat diet. Consequently the DGAT isoforms are potential therapeutic targets for the treatment of obesity and diabetes.
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