Thematic review series: Glycerolipids. DGAT enzymes and triacylglycerol biosynthesis
Open accessAbstract
Triacylglycerols (triglycerides) (TGs) are the major storage molecules of metabolic energy and FAs in most living organisms. Excessive accumulation of TGs, however, is associated with human diseases, such as obesity, diabetes mellitus, and steatohepatitis. The final and the only committed step in the biosynthesis of TGs is catalyzed by acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. The genes encoding two DGAT enzymes, DGAT1 and DGAT2, were identified in the past decade, and the use of molecular tools, including mice deficient in either enzyme, has shed light on their functions. Although DGAT enzymes are involved in TG synthesis, they have distinct protein sequences and differ in their biochemical, cellular, and physiological functions. Both enzymes may be useful as therapeutic targets for diseases. Here we review the current knowledge of DGAT enzymes, focusing on new advances since the cloning of their genes, including possible roles in human health and diseases.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The conversion of FFAs to triacylglycerols can occur via two major pathways: the glycerol phosphatase pathway or the monoacylglycerol pathway.
“The conversion of FFAs to TGs can occur via two major pathways involving several intermediates: 1) the glycerol phosphatase pathway or 2) the monoacylglycerol pathway”
From Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease (2025) · cites this paper as [49]
Unlike LXR, ACSL1 and other upstream acyltransferases, the activity of DGAT2 is the final rate-limiting step for the biosynthesis of triacylglycerols from diacylglycerols.
“Unlike LXR, ACSL1 and other upstream acyltransferases, (such as GPAT and AGPAT, that are involved in the glycerol phosphatase pathway), the activity of DGAT2 is the final rate-limiting step for the biosynthesis of TGs from DGs.49”
From Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease (2025) · cites this paper as [49]
Cites
A human retinoic acid receptor which belongs to the family of nuclear receptors
Petkovich, M., Brand, N. J., Krust, A., & Chambon, P. (1987) · Nature · doi:10.1038/330444a0 · Cited by 2,214 · see citing works
Identification of a receptor for the morphogen retinoic acid
Giguere, V., Ong, E. S., Segui, P., & Evans, R. M. (1987) · Nature · doi:10.1038/330624a0 · Cited by 1,965 · see citing works
9-cis retinoic acid is a high affinity ligand for the retinoid X receptor
Heyman, R. A., Mangelsdorf, D. J., Dyck, J. A., Stein, R. B., Eichele, G., Evans, R. M., & Thaller, C. (1992) · Cell · doi:10.1016/0092-8674(92)90479-v · Cited by 1,780 · see citing works
Unger, R. H. (2002) · Annual Review of Medicine · doi:10.1146/annurev.med.53.082901.104057 · Cited by 875 · see citing works
Cloning of DGAT2, a Second Mammalian Diacylglycerol Acyltransferase, and Related Family Members
Cases, S., Stone, S. J., Zhou, P., Yen, E., Tow, B., Lardizabal, K. D., Voelker, T., & Farese, R. V. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106219200 · Cited by 818 · see citing works
Self-citationChoi, C. S., Savage, D. B., Kulkarni, A., Yu, X. X., Liu, Z.-X., Morino, K., Kim, S., Distefano, A., Samuel, V. T., Neschen, S., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704213200 · Cited by 383 · see citing works
DGAT2 Is a New Diacylglycerol Acyltransferase Gene Family
Lardizabal, K. D., Mai, J. T., Wagner, N. W., Wyrick, A., Voelker, T., & Hawkins, D. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106168200 · Cited by 371 · see citing works
Liu, L., Zhang, Y., Chen, N., Shi, X., Tsang, B., & Yu, Y.-H. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30565 · Cited by 356 · see citing works
Very-low-density lipoprotein assembly and secretion
Shelness, G. S., & Sellers, J. A. (2001) · Current Opinion in Lipidology · doi:10.1097/00041433-200104000-00008 · Cited by 309 · see citing works
<i>DGAT1</i> polymorphism in <i>Bos indicus</i> and <i>Bos taurus</i> cattle breeds
Kaupe, B., Winter, A., Fries, R., & Erhardt, G. (2004) · Journal of Dairy Research · doi:10.1017/s0022029904000032 · Cited by 124 · see citing works
Up-regulation of SREBP-1c and lipogenic genes in skeletal muscles after exercise training
Ikeda, S., Miyazaki, H., Nakatani, T., Kai, Y., Kamei, Y., Miura, S., Tsuboyama-Kasaoka, N., & Ezaki, O. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00883-5 · Cited by 92 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Neuschwander‐Tetri, B. A. (2010) · Hepatology · doi:10.1002/hep.23719 · Cited by 1,077 · see citing works
Endoplasmic reticulum stress signalling-from basic mechanisms to clinical applications
Almanza, A., Carlesso, A., Chintha, C., Creedican, S., Doultsinos, D., Leuzzi, B., Luís, A., McCarthy, N., Montibeller, L., More, S., et al. (2019) · The FEBS Journal · doi:10.1111/febs.14608 · Cited by 1,034 · see citing works
Iqbal, J., & Hussain, M. M. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90899.2008 · Cited by 811 · see citing works
Martinez-Guryn, K., Hubert, N., Frazier, K., Urlass, S., Musch, M. W., Ojeda, P., Pierre, J. F., Miyoshi, J., Sontag, T. J., Cham, C. M., et al. (2018) · Cell Host & Microbe · doi:10.1016/j.chom.2018.03.011 · Cited by 663 · see citing works
Stone, S. J., Levin, M. C., Zhou, P., Han, J., Walther, T. C., & Farese, R. V. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m805768200 · Cited by 390 · see citing works
Self-citationRole of lipids in the formation and maintenance of the cutaneous permeability barrier
Feingold, K. R., & Elias, P. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.11.007 · Cited by 383 · see citing works
Renewable energy from Cyanobacteria: energy production optimization by metabolic pathway engineering
Quintana, N., Van der Kooy, F., Van de Rhee, M. D., Voshol, G. P., & Verpoorte, R. (2011) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-011-3394-0 · Cited by 338 · see citing works
Hashidate-Yoshida, T., Harayama, T., Hishikawa, D., Morimoto, R., Hamano, F., Tokuoka, S. M., Eto, M., Tamura-Nakano, M., Yanobu-Takanashi, R., Mukumoto, Y., et al. (2015) · eLife · doi:10.7554/elife.06328 · Cited by 270 · see citing works
Zienkiewicz, K., Du, Z.-Y., Ma, W., Vollheyde, K., & Benning, C. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2016.02.008 · Cited by 225 · see citing works
From Lipids to Inflammation: New Approaches to Reducing Atherosclerotic Risk
Shapiro, M. D., & Fazio, S. (2016) · Circulation Research · doi:10.1161/circresaha.115.306471 · Cited by 217 · see citing works
Raman-guided subcellular pharmaco-metabolomics for metastatic melanoma cells
Du, J., Su, Y., Qian, C., Yuan, D., Miao, K., Lee, D., Ng, A. H. C., Wijker, R. S., Ribas, A., Levine, R. D., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18376-x · Cited by 171 · see citing works
Structure and mechanism of human diacylglycerol O-acyltransferase 1
Wang, L., Qian, H., Nian, Y., Han, Y., Ren, Z., Zhang, H., Hu, L., Prasad, B. V. V., Laganowsky, A., Yan, N., et al. (2020) · Nature · doi:10.1038/s41586-020-2280-2 · Cited by 123 · see citing works
Structure and catalytic mechanism of a human triacylglycerol-synthesis enzyme
Sui, X., Wang, K., Gluchowski, N. L., Elliott, S. D., Liao, M., Walther, T. C., & Farese, R. V. (2020) · Nature · doi:10.1038/s41586-020-2289-6 · Cited by 120 · see citing works
Self-citationKiefer, F. W., Neschen, S., Pfau, B., Legerer, B., Neuhofer, A., Kahle, M., Hrabé de Angelis, M., Schlederer, M., Mair, M., Kenner, L., et al. (2011) · Diabetologia · doi:10.1007/s00125-011-2170-0 · Cited by 104 · see citing works
Prakash, P., Manchanda, P., Paouri, E., Bisht, K., Sharma, K., Rajpoot, J., Wendt, V., Hossain, A., Wijewardhane, P. R., Randolph, C. E., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.04.029 · Cited by 104 · see citing works
Futatsugi, K., Kung, D. W., Orr, S. T. M., Cabral, S., Hepworth, D., Aspnes, G., Bader, S., Bian, J., Boehm, M., Carpino, P. A., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01006 · Cited by 88 · see citing works
Adipocyte Fatty Acid Storage Factors Enhance Subcutaneous Fat Storage in Postmenopausal Women
Santosa, S., & Jensen, M. D. (2013) · Diabetes · doi:10.2337/db12-0912 · Cited by 82 · see citing works
Effects of Male Hypogonadism on Regional Adipose Tissue Fatty Acid Storage and Lipogenic Proteins
Santosa, S., & Jensen, M. D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031473 · Cited by 41 · see citing works
Riis, S., Christensen, B., Nellemann, B., Møller, A. B., Husted, A. S., Pedersen, S. B., Schwartz, T. W., Jørgensen, J. O. L., & Jessen, N. (2019) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00989.2018 · Cited by 39 · see citing works
Acute Testosterone Deficiency Alters Adipose Tissue Fatty Acid Storage
Santosa, S., Bush, N. C., & Jensen, M. D. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-00757 · Cited by 37 · see citing works
Nakagawa, T., Ramdhan, D. H., Tanaka, N., Naito, H., Tamada, H., Ito, Y., Li, Y., Hayashi, Y., Yamagishi, N., Yanagiba, Y., et al. (2012) · Archives of Toxicology · doi:10.1007/s00204-011-0704-3 · Cited by 33 · see citing works
Prenatal transportation stress alters genome-wide DNA methylation in suckling Brahman bull calves1,2
Littlejohn, B. P., Price, D. M., Neuendorff, D. A., Carroll, J. A., Vann, R. C., Riggs, P. K., Riley, D. G., Long, C. R., Welsh, T. H., & Randel, R. D. (2018) · Journal of Animal Science · doi:10.1093/jas/sky350 · Cited by 31 · see citing works
Parameter adaptations during phenotype transitions in progressive diseases
Tiemann, C. A., Vanlier, J., Hilbers, P. A., & van Riel, N. A. (2011) · BMC Systems Biology · doi:10.1186/1752-0509-5-174 · Cited by 22 · see citing works
Lee, J., Hong, S.-W., Kim, M.-J., Moon, S. J., Kwon, H., Park, S. E., Rhee, E.-J., & Lee, W.-Y. (2022) · Endocrinology and Metabolism · doi:10.3803/enm.2021.1293 · Cited by 20 · see citing works
Acute Female Hypogonadism Alters Adipose Tissue Fatty Acid Storage Factors and Chylomicronemia
Santosa, S., Bonnes, S. L., & Jensen, M. D. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-4065 · Cited by 16 · see citing works
Advances and Emerging Therapies in the Treatment of Non-alcoholic Steatohepatitis
Brennan, P. N., The University of Edinburgh, C. F. R. M., NHS Tayside, N. H. A. M. S., The University of Dundee, D. O. M. A. C. M., Dillon, J. F., NHS Tayside, N. H. A. M. S., The University of Dundee, D. O. M. A. C. M., McCrimmon, R., NHS Tayside, N. H. A. M. S., & The University of Dundee, D. O. M. A. C. M. (2022) · European Endocrinology · doi:10.17925/ee.2022.18.2.148 · Cited by 3 · see citing works
- Authors
- Yen, C.-L. E., Stone, S. J., Koliwad, S., Harris, C., & Farese, R. V.
- Affiliations
- University of Wisconsin–Madison (US)
- University of Saskatchewan (CA)
- University of California, San Francisco (US)
- Corresponding author
- Farese, Robert V.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 49
- Issue
- 11
- Pages
- 2283-2301
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC3837458
- OpenAlex
- W2011185005
- Cited by
- 1,105
- References
- 11
- Citations by year
- 2026: 60 · 2025: 57 · 2024: 75 · 2023: 63 · 2022: 68 · 2021: 70 · 2020: 87 · 2019: 69 · 2018: 71 · 2017: 53 · 2016: 64 · 2015: 51 · 2014: 53 · 2013: 67 · 2012: 69
- FWCI
- 3.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-56084, R01DK056084, R56DK056084)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- diacylglycerol acyltransferase, triglyceride synthesis, DGAT1, DGAT2, glycerolipids, fat deposition, obesity, diabetes mellitus, steatohepatitis, therapeutic target, knockout mice
- MeSH terms
- Animals, Glycerol, Humans, Isoenzymes, Triglycerides, Lipogenesis, Diacylglycerol O-Acyltransferase
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
