Disease relevance of Dgat2

• Induction of adipocyte hypertrophy in vitro up-regulated both DGAT1 and DGAT2 expression in 3T3-L1 cells, suggesting that adipocyte non-autonomous mechanism in vivo is required for the reciprocal changes in expression of DGAT1 and DGAT2 [1].
• DGAT2 ASO treatment did not cause significant changes in body weight, adiposity, metabolic rate, insulin sensitivity, or skin microstructure [2].

High impact information on Dgat2

• In this study, we investigated the role of acyl-coenzyme A:diacylglycerol acyltransferase 2 (DGAT2) in glucose and lipid metabolism in obese mice by reducing its expression in liver and fat with an optimized antisense oligonucleotide (ASO) [2].
• In conclusion, reduction of DGAT2 expression in obese animals can reduce hepatic lipogenesis and hepatic steatosis as well as attenuate hyperlipidemia, thereby leading to an improvement in metabolic syndrome [2].
• However, DGAT2 ASO treatment caused a marked reduction in hepatic triglyceride content and improved hepatic steatosis in both models, which was consistent with a dramatic decrease in triglyceride synthesis and an increase in fatty acid oxidation observed in primary mouse hepatocytes treated with DGAT2 ASO [2].
• Screening for transcripts of genes involved in fatty acid and triglyceride synthesis to investigate the mechanism of the hypertrophic change in the adipocytes showed that expression of DGAT2 mRNA was up-regulated in the white adipose tissue (WAT) of Irs2-/- mice, whereas that of DGAT1 was down-regulated [1].
• Expression of DGAT2 in white adipose tissue is regulated by central leptin action [1].

Biological context of Dgat2

• DGAT2-deficient (Dgat2(-/-)) mice are lipopenic and die soon after birth, apparently from profound reductions in substrates for energy metabolism and from impaired permeability barrier function in the skin [3].
• To examine the roles of liver DGAT1 and DGAT2 in TG synthesis and very low density lipoprotein (VLDL) secretion, liver DGAT1- and DGAT2-overexpressing mice were created by adenovirus-mediated gene transfection [4].
• Although both DGAT1 and DGAT2 knockout mice have reduced tissue triacylglycerol contents, they have disparate phenotypes, prompting us to investigate whether the two enzymes have unrecognized functional differences [5].
• The hMGAT2 gene is localized on chromosome 11q13.5, adjacent to the DGAT2 gene, suggesting gene duplication [6].
• DGAT2 catalyzes the final step in the production of triglycerides and the accumulation of triglycerides in the tissues is considered to be related to insulin resistance [7].

Anatomical context of Dgat2

• DGAT2 protein was detected on endoplasmic reticulum [7].
• DGAT2 mRNA was expressed in sebaceous glands of normal human skin [7].
• DGAT2 mRNA was increased in the adipose, small intestine, and skeletal muscle in diabetic mice [7].

Associations of Dgat2 with chemical compounds

• Analysis of intestine from Dgat1(-/-) mice revealed activity for two other enzymes, DGAT2 and diacylglycerol transacylase, that catalyze triacylglycerol synthesis and apparently help to compensate for the absence of DGAT1 [8].
• In the current study, we report that glucose preferentially enhances DGAT1 mRNA expression, whereas insulin specifically increases the level of DGAT2 mRNA [9].

Other interactions of Dgat2

• LXRalpha protein was increased, and its binding activity was decreased in livers of old males, while livers of old females showed an increase in DGAT1 (2.6-fold) and DGAT2 (4.9-fold) mRNA, with respect to 3-month old animals [10].

References