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Diglyceride acyltransferase
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<h2 id="isoforms">Isoforms</h2> <p>Two important DGAT <a href="/facts/Isozyme/WE3tbEhf">isozymes</a> are encoded by the genes <a href="/facts/DGAT1/LhEA47lx">DGAT1</a><a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> and DGAT2.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> Although both isozymes catalyze similar reactions, they share no sequence homology, which is similar to other DGATs reported in various organisms.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> The location of DGAT1 and DGAT2 in other organisms, as well as other DGATs have been reported in various literatures.<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> </p><p><a href="https://www.ncbi.nlm.nih.gov/gene/8694">DGAT1</a> is mainly located in absorptive <a href="/facts/Enterocyte/NfAsbB9s">enterocyte</a> cells that line the intestine and duodenum where it reassembles <a href="/facts/Triglyceride/BQmjv4A0">triglycerides</a> that were decomposed through lipolysis in the process of intestinal absorption. DGAT1 reconstitutes triglycerides in a committed step after which they are packaged together with cholesterol and proteins to form <a href="/facts/Chylomicrons/YPkGLpI6">chylomicrons</a>. </p><p><a href="https://www.ncbi.nlm.nih.gov/gene/84649">DGAT2</a> is mainly located in fat, liver and skin cells. </p> <h2 id="knockout-studies-in-mice">Knockout studies in mice</h2> <p>Mice with genetic disruption of the <i>DGAT1</i> or <i>DGAT2</i> genes have been made by the Farese laboratory at <a href="/facts/UCSF/tPU2yHuW">UCSF</a>. Surprisingly, DGAT1−/− mice<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> are healthy and fertile and have no changes in triglyceride levels. These mice are also lean and resistant to diet-induced obesity, consequently generating interest in DGAT1 inhibitors for the treatment of obesity. However, these mice also fail to <a href="/facts/Lactation/0w1HoW27">lactate</a>, showing a complete lack of milk production due to their inability to produce milk lipid droplets.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> In contrast, DGAT2−/− mice<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> have reduced triglyceride levels but are lipopenic, suffer from skin barrier abnormalities (including the inability to retain moisture), and die shortly after birth. </p> <h2 id="therapeutic-application">Therapeutic application</h2> <p>DGAT1 inhibitors have potential for the treatment of <a href="/facts/Obesity/RBF9y5Vl">obesity</a><a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a><a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a> and a number of DGAT-1 inhibitors are in <a href="/facts/Clinical_trials/q8LMr832">clinical trials</a> for this indication.<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a> </p><p>DGAT is also important in lipid biotechnology in plants, microorganisms, and animals.<a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a> </p> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Chen G, Harwood JL, Lemieux MJ, Stone SJ, Weselake RJ (November 2022). "Acyl-CoA:diacylglycerol acyltransferase: Properties, physiological roles, metabolic engineering and intentional control". Progress in Lipid Research. 88: 101181. doi:10.1016/j.plipres.2022.101181. PMID 35820474. <a href="https://doi.org/10.1016%2Fj.plipres.2022.101181" target="_blank">https://doi.org/10.1016%2Fj.plipres.2022.101181</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Yen CL, Stone SJ, Koliwad S, Harris C, Farese RV (2008). "Thematic Review Series: Glycerolipids. DGAT enzymes and triacylglycerol biosynthesis". Journal of Lipid Research. 49 (11): 2283–2301. doi:10.1194/jlr.R800018-JLR200. PMC 3837458. PMID 18757836. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837458" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837458</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Chen G, Harwood JL, Lemieux MJ, Stone SJ, Weselake RJ (November 2022). "Acyl-CoA:diacylglycerol acyltransferase: Properties, physiological roles, metabolic engineering and intentional control". Progress in Lipid Research. 88: 101181. doi:10.1016/j.plipres.2022.101181. PMID 35820474. <a href="https://doi.org/10.1016%2Fj.plipres.2022.101181" target="_blank">https://doi.org/10.1016%2Fj.plipres.2022.101181</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Oelkers P, Behari A, Cromley D, Billheimer JT, Sturley SL (October 1998). "Characterization of two human genes encoding acyl coenzyme A:cholesterol acyltransferase-related enzymes". The Journal of Biological Chemistry. 273 (41): 26765–71. doi:10.1074/jbc.273.41.26765. PMID 9756920. <a href="https://doi.org/10.1074%2Fjbc.273.41.26765" target="_blank">https://doi.org/10.1074%2Fjbc.273.41.26765</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Cases S, Stone SJ, Zhou P, Yen E, Tow B, Lardizabal KD, Voelker T, Farese RV (October 2001). "Cloning of DGAT2, a second mammalian diacylglycerol acyltransferase, and related family members". The Journal of Biological Chemistry. 276 (42): 38870–6. doi:10.1074/jbc.M106219200. PMID 11481335. <a href="https://doi.org/10.1074%2Fjbc.M106219200" target="_blank">https://doi.org/10.1074%2Fjbc.M106219200</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Chen G, Harwood JL, Lemieux MJ, Stone SJ, Weselake RJ (November 2022). "Acyl-CoA:diacylglycerol acyltransferase: Properties, physiological roles, metabolic engineering and intentional control". Progress in Lipid Research. 88: 101181. doi:10.1016/j.plipres.2022.101181. PMID 35820474. <a href="https://doi.org/10.1016%2Fj.plipres.2022.101181" target="_blank">https://doi.org/10.1016%2Fj.plipres.2022.101181</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Chen G, Harwood JL, Lemieux MJ, Stone SJ, Weselake RJ (November 2022). "Acyl-CoA:diacylglycerol acyltransferase: Properties, physiological roles, metabolic engineering and intentional control". Progress in Lipid Research. 88: 101181. doi:10.1016/j.plipres.2022.101181. PMID 35820474. <a href="https://doi.org/10.1016%2Fj.plipres.2022.101181" target="_blank">https://doi.org/10.1016%2Fj.plipres.2022.101181</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Smith SJ, Cases S, Jensen DR, Chen HC, Sande E, Tow B, Sanan DA, Raber J, Eckel RH, Farese RV (May 2000). "Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat". Nature Genetics. 25 (1): 87–90. doi:10.1038/75651. PMID 10802663. S2CID 10043699. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Smith SJ, Cases S, Jensen DR, Chen HC, Sande E, Tow B, Sanan DA, Raber J, Eckel RH, Farese RV (May 2000). "Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat". Nature Genetics. 25 (1): 87–90. doi:10.1038/75651. PMID 10802663. S2CID 10043699. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Stone SJ, Myers HM, Watkins SM, Brown BE, Feingold KR, Elias PM, Farese RV (March 2004). "Lipopenia and skin barrier abnormalities in DGAT2-deficient mice". The Journal of Biological Chemistry. 279 (12): 11767–76. doi:10.1074/jbc.M311000200. PMID 14668353. <a href="https://doi.org/10.1074%2Fjbc.M311000200" target="_blank">https://doi.org/10.1074%2Fjbc.M311000200</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Chen HC, Farese RV (March 2005). "Inhibition of triglyceride synthesis as a treatment strategy for obesity: lessons from DGAT1-deficient mice". Arteriosclerosis, Thrombosis, and Vascular Biology. 25 (3): 482–6. doi:10.1161/01.ATV.0000151874.81059.ad. PMID 15569818. <a href="https://doi.org/10.1161%2F01.ATV.0000151874.81059.ad" target="_blank">https://doi.org/10.1161%2F01.ATV.0000151874.81059.ad</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Cheng D, Iqbal J, Devenny J, Chu CH, Chen L, Dong J, Seethala R, Keim WJ, Azzara AV, Lawrence RM, Pelleymounter MA, Hussain MM (October 2008). "Acylation of acylglycerols by acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1). Functional importance of DGAT1 in the intestinal fat absorption". The Journal of Biological Chemistry. 283 (44): 29802–11. doi:10.1074/jbc.M800494200. PMC 2662058. PMID 18768481. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662058" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662058</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>"Pfizer, Bristol finalize deal on metabolic drugs". Reuters. 2007-08-27. Retrieved 2007-08-27. <a href="https://www.reuters.com/article/health-SP/idUSN2743563720070827" target="_blank">https://www.reuters.com/article/health-SP/idUSN2743563720070827</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>Chen G, Harwood JL, Lemieux MJ, Stone SJ, Weselake RJ (November 2022). "Acyl-CoA:diacylglycerol acyltransferase: Properties, physiological roles, metabolic engineering and intentional control". Progress in Lipid Research. 88: 101181. doi:10.1016/j.plipres.2022.101181. PMID 35820474. <a href="https://doi.org/10.1016%2Fj.plipres.2022.101181" target="_blank">https://doi.org/10.1016%2Fj.plipres.2022.101181</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> </ol>