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Gene Review

DGAT1  -  diacylglycerol O-acyltransferase 1

Homo sapiens

Synonyms: ACAT-related gene product 1, AGRP1, ARAT, ARGP1, Acyl-CoA retinol O-fatty-acyltransferase, ...
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Disease relevance of DGAT1

  • DGAT1-deficient mice are resistant to diet-induced obesity through a mechanism involving increased energy expenditure [1].
  • Overexpression of human DGAT1 in rat hepatoma McA-RH7777 cells resulted in increased synthesis, cellular accumulation, and secretion of TG [2].
  • On the other hand, forced overexpression of DGAT1 mRNA by >20-fold via a recombinant adenovirus only resulted in approximately 2-fold increase in DGAT1 protein in mature adipocytes and little increase in preadipocytes [3].
  • In response to a high-fat diet, aP2-Dgat1 mice became more obese ( approximately 20% greater body weight after 15 weeks) than WT mice [4].
  • Using recombinant murine MGAT2 expressed in Escherichia coli, we demonstrated conclusively that MGAT2 also possessed an intrinsic acyl-CoA:diacylglycerol acyltransferase (DGAT) activity, which could provide an alternative pathway for triacylglycerol synthesis in the absence of DGAT [5].

High impact information on DGAT1

  • Importantly, DGAT1 deficiency protects against insulin resistance and obesity in agouti yellow mice, a model of severe leptin resistance [1].
  • Acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) is one of two known DGAT enzymes that catalyze the final step in mammalian triglyceride synthesis [1].
  • Expression of DGAT1 and DGAT2 in yeast produced different types and proportions of TAGs containing eleostearic acid, with DGAT2 possessing an enhanced propensity for the synthesis of trieleostearin, the main component of tung oil [6].
  • Both DGAT1 and DGAT2 are located in distinct, dynamic regions of the endoplasmic reticulum (ER), and surprisingly, these regions do not overlap [6].
  • Acyl CoA:diacylglycerol acyltransferase (DGAT, EC catalyzes the terminal and only committed step in triacylglycerol synthesis, by using diacylglycerol and fatty acyl CoA as substrates [7].

Chemical compound and disease context of DGAT1

  • Thus, DGAT1 overexpression in murine WAT provides a model in which obesity does not impair glucose disposal [4].
  • Mice lacking acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), an enzyme that catalyzes the terminal step in triacylglycerol synthesis, have enhanced insulin sensitivity and are protected from obesity, a result of increased energy expenditure [8].
  • Inhibition of triglyceride synthesis as a treatment strategy for obesity: lessons from DGAT1-deficient mice [9].
  • Using human hepatoblastoma (HepG2) cells, we examined the effect of gemfibrozil on apo B secretion and TG synthesis catalyzed by diacylglycerol acyltransferase (DGAT), primary processes associated with the secretion of LDL [10].

Biological context of DGAT1


Anatomical context of DGAT1

  • To test this hypothesis, we stably overexpressed the DGAT1 mouse gene in human lung SV40-transformed fibroblasts (DGAT cells), which contains high levels of DAG [13].
  • Finally, the DGAT1 expression levels were closely related to the TNF-alpha level in 3T3-L1 adipocytes [14].
  • ARGP1 was expressed in numerous human adult tissues and tissue culture cell lines, whereas expression of ARGP2 was more restricted [12].
  • We investigated the regulation of the expression and function of DGAT1 in mouse 3T3-L1 cell as a model for mammalian adipocytes [3].
  • In the differentiated Caco-2 cell membranes, XP620 inhibits approximately 85% of the Caco-2/ARAT activity indicating that DGAT1/ARAT may be the major source of ARAT activity in these cells [15].

Associations of DGAT1 with chemical compounds

  • VLDL secreted from DGAT1-expressing cells incubated in OA had a higher TG:CE ratio than VLDL secreted from ACAT1- and ACAT2-expressing cells treated with OA [2].
  • These data suggest that niacin directly and noncompetitively inhibits DGAT2 but not DGAT1, resulting in decreased triglyceride synthesis and hepatic atherogenic lipoprotein secretion, thus indicating a major target site for its mechanism of action [16].
  • Niacin selectively inhibited DGAT2 but not DGAT1 activity [16].
  • The expression of TNF-alpha, DGAT1, and DGAT2 were upregulated in adipocytes cultured with 25mM glucose [14].
  • In contrast to human DGAT1 lacking fatty acid specificity, TgDGAT1 preferentially incorporates palmitate [17].

Other interactions of DGAT1

  • Niacin had no effect on the expression of DGAT1 and DGAT2 mRNA [16].
  • MEK1/2 inhibition significantly increased both cellular and microsomal TG mass, and mRNA levels for DGAT-1 and DGAT-2 [18].
  • The expression of DGAT1, PPAR-gamma, and HSL was enhanced [19].
  • AcylCoA:cholesterol acyltransferase (ACAT) and diacylglycerol acyltransferase (DGAT) activities measured on cell-free extracts appeared to be decreased also by phospholipid polar head group modification, whereas the overall phospholipid acyltransferase activity remained unchanged [20].
  • Both AGRP1 and AGRP2 showed genomic synteny with the human AGRP gene [21].

Analytical, diagnostic and therapeutic context of DGAT1


  1. Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1. Chen, H.C., Smith, S.J., Ladha, Z., Jensen, D.R., Ferreira, L.D., Pulawa, L.K., McGuire, J.G., Pitas, R.E., Eckel, R.H., Farese, R.V. J. Clin. Invest. (2002) [Pubmed]
  2. Overexpression of human diacylglycerol acyltransferase 1, acyl-coa:cholesterol acyltransferase 1, or acyl-CoA:cholesterol acyltransferase 2 stimulates secretion of apolipoprotein B-containing lipoproteins in McA-RH7777 cells. Liang, J.J., Oelkers, P., Guo, C., Chu, P.C., Dixon, J.L., Ginsberg, H.N., Sturley, S.L. J. Biol. Chem. (2004) [Pubmed]
  3. Posttranscriptional control of the expression and function of diacylglycerol acyltransferase-1 in mouse adipocytes. Yu, Y.H., Zhang, Y., Oelkers, P., Sturley, S.L., Rader, D.J., Ginsberg, H.N. J. Biol. Chem. (2002) [Pubmed]
  4. Dissociation of obesity and impaired glucose disposal in mice overexpressing acyl coenzyme a:diacylglycerol acyltransferase 1 in white adipose tissue. Chen, H.C., Stone, S.J., Zhou, P., Buhman, K.K., Farese, R.V. Diabetes (2002) [Pubmed]
  5. Properties of the mouse intestinal acyl-CoA:monoacylglycerol acyltransferase, MGAT2. Cao, J., Burn, P., Shi, Y. J. Biol. Chem. (2003) [Pubmed]
  6. Tung Tree DGAT1 and DGAT2 Have Nonredundant Functions in Triacylglycerol Biosynthesis and Are Localized to Different Subdomains of the Endoplasmic Reticulum. Shockey, J.M., Gidda, S.K., Chapital, D.C., Kuan, J.C., Dhanoa, P.K., Bland, J.M., Rothstein, S.J., Mullen, R.T., Dyer, J.M. Plant Cell (2006) [Pubmed]
  7. Identification of a gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis. Cases, S., Smith, S.J., Zheng, Y.W., Myers, H.M., Lear, S.R., Sande, E., Novak, S., Collins, C., Welch, C.B., Lusis, A.J., Erickson, S.K., Farese, R.V. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  8. Effects of DGAT1 deficiency on energy and glucose metabolism are independent of adiponectin. Streeper, R.S., Koliwad, S.K., Villanueva, C.J., Farese, R.V. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  9. Inhibition of triglyceride synthesis as a treatment strategy for obesity: lessons from DGAT1-deficient mice. Chen, H.C., Farese, R.V. Arterioscler. Thromb. Vasc. Biol. (2005) [Pubmed]
  10. Effect of gemfibrozil on apolipoprotein B secretion and diacylglycerol acyltransferase activity in human hepatoblastoma (HepG2) cells. Zhu, D., Ganji, S.H., Kamanna, V.S., Kashyap, M.L. Atherosclerosis (2002) [Pubmed]
  11. DGAT1 promoter polymorphism associated with alterations in body mass index, high density lipoprotein levels and blood pressure in Turkish women. Ludwig, E.H., Mahley, R.W., Palaoglu, E., Ozbayrakçi, S., Balestra, M.E., Borecki, I.B., Innerarity, T.L., Farese, R.V. Clin. Genet. (2002) [Pubmed]
  12. Characterization of two human genes encoding acyl coenzyme A:cholesterol acyltransferase-related enzymes. Oelkers, P., Behari, A., Cromley, D., Billheimer, J.T., Sturley, S.L. J. Biol. Chem. (1998) [Pubmed]
  13. Overexpression of diacylglycerol acyltransferase-1 reduces phospholipid synthesis, proliferation, and invasiveness in simian virus 40-transformed human lung fibroblasts. Bagnato, C., Igal, R.A. J. Biol. Chem. (2003) [Pubmed]
  14. Activation of diacylglycerol O-acyltransferase 1 gene results in increased tumor necrosis factor-alpha gene expression in 3T3-L1 adipocytes. Hirata, T., Unoki, H., Bujo, H., Ueno, K., Saito, Y. FEBS Lett. (2006) [Pubmed]
  15. Acyl coenzyme A dependent retinol esterification by acyl coenzyme A: diacylglycerol acyltransferase 1. Orland, M.D., Anwar, K., Cromley, D., Chu, C.H., Chen, L., Billheimer, J.T., Hussain, M.M., Cheng, D. Biochim. Biophys. Acta (2005) [Pubmed]
  16. Niacin noncompetitively inhibits DGAT2 but not DGAT1 activity in HepG2 cells. Ganji, S.H., Tavintharan, S., Zhu, D., Xing, Y., Kamanna, V.S., Kashyap, M.L. J. Lipid Res. (2004) [Pubmed]
  17. On the biogenesis of lipid bodies in ancient eukaryotes: synthesis of triacylglycerols by a Toxoplasma DGAT1-related enzyme. Quittnat, F., Nishikawa, Y., Stedman, T.T., Voelker, D.R., Choi, J.Y., Zahn, M.M., Murphy, R.C., Barkley, R.M., Pypaert, M., Joiner, K.A., Coppens, I. Mol. Biochem. Parasitol. (2004) [Pubmed]
  18. MEK-ERK inhibition corrects the defect in VLDL assembly in HepG2 cells: potential role of ERK in VLDL-ApoB100 particle assembly. Tsai, J., Qiu, W., Kohen-Avramoglu, R., Adeli, K. Arterioscler. Thromb. Vasc. Biol. (2007) [Pubmed]
  19. Evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease. Nakamuta, M., Kohjima, M., Morizono, S., Kotoh, K., Yoshimoto, T., Miyagi, I., Enjoji, M. Int. J. Mol. Med. (2005) [Pubmed]
  20. Modification of phospholipid polar head group with monomethylethanolamine and dimethylethanolamine decreases cholesteryl ester and triacylglycerol synthesis in cultured human fibroblasts. Maziere, C., Auclair, M., Mora, L., Maziere, J.C. Lipids (1990) [Pubmed]
  21. Characterization and tissue distribution of multiple agouti-family genes in pufferfish, Takifugu rubripes. Kurokawa, T., Murashita, K., Uji, S. Peptides (2006) [Pubmed]
  22. Exclusion of the acyl CoA:diacylglycerol acyltransferase 1 gene (DGAT1) as a candidate for a fatty acid composition QTL on porcine chromosome 4. Mercadé, A., Sánchez, A., Folch, J.M. J. Anim. Breed. Genet. (2005) [Pubmed]
  23. Human acyl-CoA:diacylglycerol acyltransferase is a tetrameric protein. Cheng, D., Meegalla, R.L., He, B., Cromley, D.A., Billheimer, J.T., Young, P.R. Biochem. J. (2001) [Pubmed]
  24. Increased diacylglycerol acyltransferase activity is associated with triglyceride accumulation in tissues of diet-induced insulin-resistant hyperlipidemic hamsters. Casaschi, A., Maiyoh, G.K., Adeli, K., Theriault, A.G. Metab. Clin. Exp. (2005) [Pubmed]
  25. Neutral lipid synthesis and storage in the intraerythrocytic stages of Plasmodium falciparum. Vielemeyer, O., McIntosh, M.T., Joiner, K.A., Coppens, I. Mol. Biochem. Parasitol. (2004) [Pubmed]
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