Affinage

DGAT1

Diacylglycerol O-acyltransferase 1 · UniProt O75907

Length
488 aa
Mass
55.3 kDa
Annotated
2026-04-28
100 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DGAT1 is an ER-resident acyltransferase that catalyzes the final committed step of triacylglycerol (TG) synthesis and additionally functions as a monoacylglycerol acyltransferase, wax synthase, and retinol acyltransferase (ARAT), with a catalytic His-426 residue in its large ER-luminal C-terminal domain (PMID:15834126, PMID:20876538). Its dual ER membrane topology enables both cytosolic and luminal TG synthesis; the luminal activity is specifically required for full VLDL lipidation in hepatocytes and for chylomicron secretion in enterocytes, while it preferentially esterifies exogenous rather than de novo–synthesized fatty acids (PMID:15797871, PMID:30397187, PMID:22493088). Beyond bulk lipid storage, DGAT1-mediated re-esterification of fatty acids released during lipolysis protects the ER from lipotoxic stress, and its ARAT activity controls retinol availability for retinoic acid–dependent regulatory T cell differentiation (PMID:28768178, PMID:30936184, PMID:30718413). Biallelic loss-of-function mutations in human DGAT1 cause congenital diarrhea and intestinal failure with impaired TG metabolism and increased susceptibility to lipid-induced cell death (PMID:29604290).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 High

    Establishing that DGAT1 is the terminal enzyme in the glycerol phosphate TG synthesis pathway and is required for normal adiposity and lactation—but is not essential for viability—defined its non-redundant physiological role and implied the existence of compensatory pathways.

    Evidence Dgat1 global knockout mice with phenotypic and tissue TG analysis

    PMID:10802663

    Open questions at the time
    • Identity and contribution of the compensating enzyme (DGAT2) not yet defined
    • Tissue-specific requirements not resolved
  2. 2004 High

    Demonstration that DGAT1 directly controls intramyocellular and mammary lipid storage, and that a naturally occurring bovine K232A polymorphism alters enzymatic Vmax, established DGAT1 activity as rate-limiting for tissue TG content and showed genetic variation at the locus has quantitative functional consequences.

    Evidence In vivo muscle electroporation gain-of-function; mammary transplantation epistasis; baculovirus reconstitution of K vs A alleles with kinetic assays

    PMID:14983021 PMID:15163627 PMID:15576838

    Open questions at the time
    • Post-translational regulation of DGAT1 activity unknown
    • Structural basis for K232A kinetic difference unresolved
  3. 2005 High

    Discovering DGAT1's multifunctional acyltransferase repertoire (MGAT, wax synthase, ARAT) and its latent luminal DGAT activity that promotes VLDL secretion revealed that the enzyme operates on both sides of the ER membrane and handles diverse lipid substrates.

    Evidence In vitro microsome assays with multiple substrates; Dgat1-KO mouse retinol metabolism; hepatic adenoviral overexpression with alamethicin-dependent activity assays and VLDL measurement

    PMID:15797871 PMID:15834126

    Open questions at the time
    • Structural basis for multisubstrate promiscuity unknown
    • Relative contribution of luminal vs cytosolic activity in vivo not quantified
  4. 2009 Medium

    Identification that DGAT1 in intestinal L-cells regulates GLP-1 and PYY secretion linked TG esterification to gut incretin signaling, expanding DGAT1's role beyond lipid storage to neuroendocrine regulation.

    Evidence Dgat1-KO and Mgat2-KO mouse oral TG loading with gut peptide measurement; DGAT/MGAT activity assays in L-cell lines

    PMID:19732742

    Open questions at the time
    • Mechanism by which intracellular TG flux regulates peptide vesicle secretion undefined
    • Contribution of DGAT1 vs other lipid metabolic steps in L-cells not fully separated
  5. 2010 High

    Elucidation of DGAT1 membrane topology (three TMDs, luminal catalytic domain with essential His-426) and demonstration that macrophage DGAT1 inversely controls inflammatory activation resolved how the enzyme is oriented in the ER and established a cell-autonomous anti-inflammatory function through FA sequestration.

    Evidence Protease protection, selective permeabilization, site-directed mutagenesis; bone marrow transplant with macrophage-specific overexpression and KO

    PMID:20124729 PMID:20147738 PMID:20876538

    Open questions at the time
    • High-resolution 3D structure not available
    • Mechanism of oligomerization via N-terminal domain not fully defined
  6. 2011 High

    Double knockout of DGAT1 and DGAT2 in adipocytes completely abolished TG and lipid droplets while single knockouts did not, formally proving functional redundancy yet also demonstrating that the two enzymes together account for virtually all adipocyte TG synthesis.

    Evidence Adipocyte-specific double KO with TG quantification and lipid droplet imaging

    PMID:21317108

    Open questions at the time
    • Whether the two enzymes occupy distinct ER subdomains not addressed
    • Lipid species specificity of each enzyme in adipocytes not resolved
  7. 2012 High

    Isotope tracing established that DGAT1 preferentially esterifies exogenous fatty acids while DGAT2 handles de novo–synthesized ones, and that intestinal DGAT1 is required for chylomicron secretion independently of gastric emptying, delineating substrate-source partitioning between the two enzymes.

    Evidence 13C-oleic acid and 13C3-D5-glycerol tracing with isoform-selective inhibitors in HepG2 and mice; intestine-specific Dgat1 KO with duodenal oil bypass

    PMID:22493088 PMID:22911105

    Open questions at the time
    • Molecular determinants of exogenous FA channeling to DGAT1 unknown
    • Whether FA source specificity holds in all tissues untested
  8. 2014 High

    Biophysical characterization of substrate-binding motifs (FYxDWWN and HKWCIRHFYKP) and demonstration that cardiomyocyte DGAT1 loss causes lethal DAG/ceramide accumulation and heart failure provided the first structure-function mapping of the active site and revealed that DGAT1-mediated DAG clearance is essential for cardiac lipid homeostasis.

    Evidence Synchrotron CD and fluorescence spectroscopy of synthetic peptides; cardiomyocyte-specific Dgat1 KO with lipidomics and cardiac function measurement

    PMID:25152099 PMID:25157099

    Open questions at the time
    • Peptide-based substrate binding studies not validated in full-length protein
    • How cardiac DGAT1 is regulated differently from adipocyte DGAT1 unclear
  9. 2017 High

    Discovery that DGAT1-mediated fatty acid re-esterification during lipolysis specifically protects the ER from lipotoxic stress—rather than preserving TG mass—redefined the enzyme's role as an ER quality-control mechanism, while identification of C/EBPα–p300 complex binding at the DGAT1 promoter established a transcriptional regulatory axis.

    Evidence Adipocyte-specific Dgat1 KO with ER stress markers under HFD; ChIP and Co-IP of C/EBPα–p300 on DGAT1 promoter in aged mouse liver

    PMID:28768178 PMID:29024407

    Open questions at the time
    • Specific ER lipid species causing stress in DGAT1-deficient cells not identified
    • Whether C/EBPα–p300 regulation is universal or tissue-specific unknown
  10. 2018 High

    Hepatocyte-specific DGAT1 deletion showed that DGAT1 determines VLDL particle size and TG content (but not particle number), linking the enzyme's luminal activity to the second-step lipidation of VLDL; separately, biallelic human DGAT1 mutations were shown to cause congenital intestinal failure with lipotoxic cell death, establishing DGAT1 deficiency as a Mendelian disease.

    Evidence DGAT1-LKO mice with VLDL particle sizing; patient-derived organoids and fibroblasts from five DGAT1-mutant families with DGAT2 rescue and CRISPR validation

    PMID:29604290 PMID:30397187

    Open questions at the time
    • How luminal TG pool is transferred to nascent VLDL particles mechanistically unresolved
    • Genotype-phenotype correlation across different human mutations not established
  11. 2019 High

    Demonstration that DGAT1's ARAT activity sequesters retinol away from retinoic acid synthesis in T cells, thereby suppressing Treg differentiation, revealed an unexpected immunoregulatory function linking lipid metabolism to adaptive immunity.

    Evidence Dgat1-KO mice in EAE model, adoptive T cell transfer, DGAT1 inhibitor, in vitro Treg induction with retinol

    PMID:30718413

    Open questions at the time
    • Whether DGAT1-dependent retinol esterification regulates other immune cell types untested
    • Relative contribution of DGAT1 ARAT vs LRAT in T cell retinol homeostasis not quantified
  12. 2021 High

    Identification of HILPDA as a direct physical interactor that stimulates DGAT1 activity provided the first protein-level positive regulator of the enzyme, suggesting allosteric or stabilizing activation mechanisms.

    Evidence FRET-FLIM in live hepatocytes confirming physical interaction; DGAT activity assays with HILPDA OE/KO

    PMID:33465519

    Open questions at the time
    • Binding interface and mechanism of HILPDA-mediated activation undefined
    • Whether HILPDA affects DGAT1 oligomeric state unknown
  13. 2022 Medium

    Discovery that the JMJD6–RBM39 epigenetic complex co-occupies the DGAT1 promoter with H3K4me3 to drive DGAT1 expression in clear cell renal cell carcinoma established a second transcriptional regulatory axis and implicated DGAT1-dependent lipid droplets in tumor biology.

    Evidence ChIP-seq, RNA-seq, Co-IP of JMJD6–RBM39, DGAT1 KD and inhibition in orthotopic ccRCC tumor models

    PMID:35764091

    Open questions at the time
    • Whether JMJD6–RBM39 regulation of DGAT1 occurs in non-malignant tissues unknown
    • Mechanism by which DGAT1-dependent LDs support ccRCC viability not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of full-length DGAT1 in complex with substrates and regulatory partners (e.g., HILPDA) is needed to explain multisubstrate promiscuity, the structural basis for oligomerization, and how phosphorylation at identified sites modulates activity.
  • No full-length human DGAT1 structure with substrates bound
  • Phosphorylation-dependent regulation not integrated with topology and structural models
  • Allosteric mechanism of HILPDA activation undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0008289 lipid binding 1
Localization
GO:0005783 endoplasmic reticulum 3
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-9609507 Protein localization 2 R-HSA-1643685 Disease 1 R-HSA-168256 Immune System 1
Partners
CEBPADGAT2EP300HILPDAJMJD6RBM39

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 DGAT1 (Dgat) catalyzes the final and only committed step in triglyceride synthesis via the glycerol phosphate pathway; Dgat-deficient mice are viable and lean, demonstrating that Dgat1 is not absolutely required for survival but is necessary for normal triglyceride synthesis in adipose tissue and for lactation Genetic knockout (Dgat-/- mice), tissue triglyceride assays, phenotypic analysis of obesity resistance and lactation defects Nature genetics High 10802663
2005 DGAT1 is a multifunctional acyltransferase: beyond triacylglycerol synthesis, it also catalyzes synthesis of diacylglycerols (monoacylglycerol acyltransferase activity), wax monoesters and wax diesters (wax synthase activity), and retinyl esters (acyl-CoA:retinol acyltransferase/ARAT activity) in vitro and in vivo In vitro acyltransferase assays with microsomes from insect cells and COS7 cells overexpressing DGAT1; intact cell assays; DGAT1-deficient mice showing reduced ARAT activity and elevated hepatic unesterified retinol Journal of lipid research High 15834126
2010 DGAT1 topology: three transmembrane domains with the N-terminus oriented toward the cytosol and the large C-terminal region (~50% of protein) residing in the ER lumen; a conserved histidine (His-426) in the luminal C-terminal domain is a putative active-site residue required for triacylglycerol, retinyl ester, and wax ester synthesis; the N-terminal domain is not required for catalytic activity but is involved in dimer/tetramer formation Protease protection assays, indirect immunofluorescence with selective membrane permeabilization, site-directed mutagenesis (H426A) with in vitro acyltransferase assays, N-terminal truncation mutants The Journal of biological chemistry High 20876538
2005 Liver-specific overexpression of DGAT1 increases DGAT activity detectable only in the presence of the permeabilizing agent alamethicin, indicating that DGAT1 possesses latent DGAT activity on the luminal face of the ER membrane; hepatic DGAT1 overexpression increases VLDL secretion, resulting in increased gonadal fat mass Adenovirus-mediated hepatic overexpression of DGAT1 in mice; DGAT activity assays with and without alamethicin permeabilization; plasma VLDL measurements; fat depot analysis The Journal of biological chemistry High 15797871
2011 DGAT1 and DGAT2 together account for nearly all triacylglycerol synthesis in adipocytes and are required for lipid droplet formation during adipogenesis; adipocytes lacking both DGATs have no TG or lipid droplets despite full differentiation; single deletion of either enzyme alone is insufficient to block TG synthesis Genetic double knockout (DGAT1 and DGAT2 adipocyte deletions), TG quantification, lipid droplet imaging, differentiation marker analysis Journal of lipid research High 21317108
2017 FA re-esterification during adipocyte lipolysis is mediated specifically by DGAT1 (ER-localized); this re-esterification cycle does not preserve TG mass but instead protects the ER from lipotoxic stress and adipose tissue inflammation; mice lacking DGAT1 in adipocytes show activated ER stress pathways specifically under high-fat diet challenge Adipocyte-specific DGAT1 knockout mice, lipolysis assays, ER stress marker analysis, adipose tissue inflammation measurements, high-fat diet challenge Cell metabolism High 28768178
2012 In hepatocytes, DGAT1 preferentially esterifies exogenous (dietary/plasma) fatty acids into TG (re-esterification pathway), while DGAT2 primarily incorporates endogenously synthesized fatty acids into TG; DGAT1 inhibition reduces incorporation of exogenous oleic acid into VLDL-TG without affecting glycerol-derived (de novo) TG synthesis Stable isotope tracing with 13C3-D5-glycerol and 13C18-oleic acid in HepG2 cells; selective DGAT1 and DGAT2 inhibitors; in vivo D5-glycerol and 13C18-oleic acid tracing in mice with DGAT2 antisense oligonucleotide knockdown; LC-MS/MS lipidomics Journal of lipid research High 22493088
2004 The bovine DGAT1 K232A polymorphism is functionally causative: the K allele has higher Vmax for triglyceride production than the A allele, as demonstrated by baculovirus expression of both alleles in Sf9 cells Baculovirus expression system in Sf9 insect cells; DGAT enzymatic kinetics (Vmax) comparing K and A alleles; high-density SNP mapping confirming DGAT1 as QTL locus Proceedings of the National Academy of Sciences of the United States of America High 14983021
2014 Cardiomyocyte-specific loss of DGAT1 causes DAG and ceramide accumulation (95% and 85% increases respectively), heart failure, and early mortality; loss of DGAT1-mediated conversion of DAG to TG leads to increased PKCα activation by accumulated DAG/ceramides; restriction of dietary fat absorption via enterocyte-specific DGAT1 KO or GLP-1 agonist exenatide corrects these lipid abnormalities and cardiac dysfunction Cardiomyocyte-specific DGAT1 KO mice; DAG and ceramide quantification; cardiac function measurements (fractional shortening, BNP); genetic epistasis with enterocyte-specific Dgat1 KO; pharmacological treatment with exenatide The Journal of biological chemistry High 25157099
2010 DGAT1 expression in macrophages determines their TG storage capacity and inversely regulates inflammatory activation by saturated fatty acids; macrophage-specific DGAT1 overexpression protects against diet-induced adipose tissue inflammation and insulin resistance; PPARγ agonist protective effects against FA-induced macrophage inflammation are absent in Dgat1-null macrophages Bone marrow transplantation, macrophage-specific overexpression (aP2-Dgat1), macrophage isolation with TG measurement, inflammatory cytokine assays, PPARγ agonist treatment of Dgat1-null macrophages The Journal of clinical investigation High 20124729
2010 Intestinal DGAT1 stimulates dietary fat secretion out of enterocytes into circulation; intestinal DGAT1 expression alone (without liver or adipose DGAT1) is sufficient to reconstitute susceptibility to high-fat diet-induced hepatic steatosis and obesity in Dgat1-/- mice Intestine-specific rescue of DGAT1 expression in Dgat1-/- mice (Dgat1IntONLY), high-fat diet challenge, hepatic steatosis measurement, obesity phenotyping Journal of lipid research High 20147738
2012 Intestinal DGAT1 inhibition or deficiency reduces postprandial TG and retinyl ester excursions by inhibiting chylomicron secretion; loss of intestinal DGAT1 activity delays gastric emptying and increases plasma GLP-1; the chylomicron secretion defect occurs independently of gastric emptying delay when lipid is delivered directly to the small intestine Intestine-specific Dgat1 KO mice, acute DGAT1 inhibitor gavage, oral fat/retinol loading, chylomicron secretion assays, GLP-1 measurement, duodenal oil injection bypass experiments Journal of lipid research High 22911105
2018 Hepatic DGAT1 determines VLDL particle size and TG content but not particle number; DGAT1-LKO hepatocytes secrete VLDL particles with half the normal TG content and size; this is consistent with DGAT1's dual ER membrane topology enabling TAG synthesis on the luminal side for full VLDL lipidation; DGAT2 can fully support apoB secretion (particle number) in absence of DGAT1 Hepatocyte-specific DGAT1 KO mice (DGAT1-LKO), Triton WR-1339 VLDL secretion assay, VLDL particle sizing, apoB concentration measurement, ER lipid content analysis by electron microscopy, HepG2 cells with isoform-selective inhibitors Journal of lipid research High 30397187
2019 DGAT1 and DGAT2 have distinct but overlapping functions in adipocytes: DGAT2-specific KO in adipocytes does not impair TG storage or glucose metabolism, while DGAT1-specific KO causes glucose intolerance and ER stress pathway activation on high-fat diets; DGAT1 uniquely protects the ER from lipotoxic stress of high-fat feeding Adipocyte-specific DGAT1 and DGAT2 KO mice, high-fat diet challenge, TG quantification, glucose tolerance tests, ER stress marker analysis Journal of lipid research High 30936184
2004 DGAT1 deficiency in mice impairs mammary gland development: decreased epithelial proliferation, alveolar development, and reduced expression of functional differentiation markers; transplantation studies show DGAT1 is required in both stromal and epithelial tissues for normal mammary development Dgat1-/- mice, mammary gland transplantation (wild-type vs. Dgat1-/- stroma/epithelium combinations), proliferation and differentiation marker analysis Development (Cambridge, England) High 15163627
2019 DGAT1 acyltransferase activity sequesters retinol as retinyl esters, thereby preventing retinol conversion to retinoic acid and suppressing retinoic acid-dependent regulatory T cell (Treg) formation; DGAT1 inhibition or deficiency in T cells enhances Treg frequency and attenuates experimental autoimmune encephalomyelitis Dgat1-/- mice in EAE model, adoptive transfer of Dgat1-/- Th17 cells, DGAT1 inhibitor treatment, in vitro Treg induction assays with retinol, T cell-depleted lymphoid tissue cultures Proceedings of the National Academy of Sciences of the United States of America High 30718413
2021 HILPDA (hypoxia-inducible lipid droplet-associated protein) physically interacts with DGAT1 in living liver cells and stimulates DGAT activity, increasing DGAT1 protein levels and promoting lipid storage in hepatocytes and adipocytes FRET-FLIM in live cells confirming physical interaction, real-time fluorescence live-cell imaging, DGAT activity assays, HILPDA overexpression and deficiency models Molecular metabolism High 33465519
2021 SARS-CoV-2 nucleocapsid protein drives DGAT1/2 gene expression to facilitate lipid droplet formation; DGAT1 gene depletion reduces SARS-CoV-2 protein synthesis without compromising viral genome replication/transcription, indicating DGAT1-dependent lipid droplets are required for a post-replication step in the viral cycle DGAT gene depletion (siRNA/CRISPR), viral protein vs. genome replication quantification, lipid droplet imaging, DGAT inhibitor xanthohumol in hamster model Cell discovery Medium 34702802
2015 DGAT1 in skeletal muscle cells is phosphorylated at multiple sites; phosphorylation at specific conserved residues regulates DGAT1 enzymatic activity; a defined N-terminal domain of DGAT1 influences regulatory activity; these phosphorylation events were confirmed by mass spectrometry of purified DGAT1 from C2C12 myoblasts Phosphorylation mass spectrometry of purified DGAT1 from C2C12 cells, site-directed mutagenesis of phosphorylation sites, truncation mutants with enzymatic activity assays Biophysics reports Medium 26942218
2014 DGAT1 substrate binding sites include a luminal loop containing the FYxDWWN motif (Sit1, shared with ACAT enzymes) that changes conformation upon binding both oleoyl-CoA and diacylglycerol substrates, and a diacylglycerol-binding domain (Sit2, HKWCIRHFYKP motif) that interacts with charged headgroups; in a peptide containing both sites, larger conformational changes are induced, suggesting the two sites bring substrates into proximity for catalysis Synchrotron radiation circular dichroism spectroscopy of synthetic peptides, fluorescence emission spectroscopy, lipid monolayer adsorption assays with substrates oleoyl-CoA and dioleoylglycerol Biochimica et biophysica acta Medium 25152299
2017 A novel DGAT1 missense mutation p.L105P causes partial loss of DGAT1 enzymatic activity and decreased TG synthesis and lipid droplet formation in patient-derived fibroblasts, demonstrating that DGAT1 protein stability and quantity affect TG synthesis capacity Exome sequencing, patient-derived primary dermal fibroblasts, DGAT1 protein abundance measurement, TG synthesis assays, lipid droplet quantification after oleic acid loading Journal of lipid research Medium 28373485
2018 Biallelic loss-of-function mutations in human DGAT1 cause intestinal failure with altered triacylglycerol metabolism, decreased lipid droplet formation, and increased susceptibility to lipid-induced cell death; expression of full-length DGAT2 in DGAT1-deficient fibroblasts restores lipid droplet formation, demonstrating functional overlap between the two enzymes Next-generation sequencing identifying 5 biallelic DGAT1 mutations, patient-derived intestinal organoids and fibroblasts, immunoblot, flow cytometry, lipid chromatography, caspase 3/7 activity assays, DGAT2 rescue experiments, CRISPR/Cas9 DGAT1 disruption in control organoids Gastroenterology High 29604290
2004 DGAT1 overexpression in skeletal muscle by in vivo electroporation directly increases intramyocellular lipid (IMCL) storage in a diet-responsive manner, demonstrating that DGAT1 activity directly controls TG storage in muscle In vivo DNA electroporation of pcDNA3.1-DGAT1 into tibialis anterior muscle, immunofluorescence for DGAT1 protein expression, quantitative IMCL analysis with lipid staining Journal of lipid research Medium 15576838
2009 DGAT1 in intestinal L-cells directly regulates GLP-1 and PYY secretion; DGAT1KO mice show prolonged GLP-1 and PYY elevation after triglyceride loading compared to wild-type, while GIP increase is suppressed; STC-1 and GLUTag L-cell lines possess DGAT1 activity but not MGAT activity DGAT1KO and MGAT2KO mouse oral triglyceride loading studies, plasma gut peptide measurements (GIP, GLP-1, PYY), gastric emptying measurements, DGAT/MGAT activity assays in L-cell lines Biochemical and biophysical research communications Medium 19732742
2017 Ghrelin deletion prevents age-associated DGAT1 upregulation in liver by reducing formation of C/EBPα-p300 transcriptional complexes that bind and activate the DGAT1 promoter; in aged wild-type mice, C/EBPα-p300 complexes bind the DGAT1 promoter and increase DGAT1 expression, driving steatosis Ghrelin KO mice, ChIP analysis showing C/EBPα-p300 occupancy of DGAT1 promoter, co-immunoprecipitation of C/EBPα-p300 complexes, DGAT1 promoter binding studies, aged mouse hepatic steatosis analysis Aging cell Medium 29024407
2022 In clear cell renal cell carcinoma, the epigenetic enzyme JMJD6 interacts with RBM39 and co-occupies the DGAT1 gene promoter with H3K4me3 to induce DGAT1 expression; DGAT1 upregulation promotes lipid droplet formation required for ccRCC tumorigenesis siRNA screen, ChIP-seq and RNA-seq integration, Co-IP of JMJD6-RBM39 interaction, DGAT1 KD and pharmacological inhibition, orthotopic tumor models in vivo Molecular cell Medium 35764091
2016 In hepatic stellate cells, DGAT1 synthesizes newly formed TAG enriched in PUFAs; ATGL preferentially degrades these newly synthesized DGAT1-dependent TAGs; DGAT1 inhibitor T863 reduces PUFA-TAG synthesis in HSCs Targeted Atgl gene deletion in mouse HSCs, DGAT1 inhibitor T863, lipidomics of TAG species, hepatic stellate cell activation assays Journal of lipid research Medium 27179362
2019 In DGAT1-deficient human intestinal stem cell organoids, DGAT2 partially compensates for lipid droplet formation; unsaturated and saturated FA-induced lipotoxicity in DGAT1-deficient cells is mediated by ER stress; DGAT2 overexpression fully rescues DGAT1 deficiency in organoids Patient-derived DGAT1-deficient intestinal organoids, DGAT2 overexpression rescue, ER stress marker analysis, lipid droplet quantification, FA lipotoxicity assays Journal of lipid research Medium 31315900

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Thematic review series: glycerolipids. DGAT enzymes and triacylglycerol biosynthesis. Journal of lipid research 843 18757836
2000 Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nature genetics 680 10802663
2006 Tung tree DGAT1 and DGAT2 have nonredundant functions in triacylglycerol biosynthesis and are localized to different subdomains of the endoplasmic reticulum. The Plant cell 392 16920778
2017 Triglyceride Synthesis by DGAT1 Protects Adipocytes from Lipid-Induced ER Stress during Lipolysis. Cell metabolism 275 28768178
2011 DGAT enzymes are required for triacylglycerol synthesis and lipid droplets in adipocytes. Journal of lipid research 268 21317108
2004 Genetic and functional confirmation of the causality of the DGAT1 K232A quantitative trait nucleotide in affecting milk yield and composition. Proceedings of the National Academy of Sciences of the United States of America 267 14983021
2020 Targeting DGAT1 Ameliorates Glioblastoma by Increasing Fat Catabolism and Oxidative Stress. Cell metabolism 266 32559414
2008 A phenylalanine in DGAT is a key determinant of oil content and composition in maize. Nature genetics 252 18278045
2005 The triacylglycerol synthesis enzyme DGAT1 also catalyzes the synthesis of diacylglycerols, waxes, and retinyl esters. Journal of lipid research 215 15834126
2010 DGAT1-dependent triacylglycerol storage by macrophages protects mice from diet-induced insulin resistance and inflammation. The Journal of clinical investigation 190 20124729
2008 Beyond triglyceride synthesis: the dynamic functional roles of MGAT and DGAT enzymes in energy metabolism. American journal of physiology. Endocrinology and metabolism 176 19116371
2004 Niacin noncompetitively inhibits DGAT2 but not DGAT1 activity in HepG2 cells. Journal of lipid research 174 15258194
2009 Tobacco as a production platform for biofuel: overexpression of Arabidopsis DGAT and LEC2 genes increases accumulation and shifts the composition of lipids in green biomass. Plant biotechnology journal 155 20051035
2018 Role of DGAT enzymes in triacylglycerol metabolism. Archives of biochemistry and biophysics 148 30077544
2011 Evolutionary view of acyl-CoA diacylglycerol acyltransferase (DGAT), a key enzyme in neutral lipid biosynthesis. BMC evolutionary biology 145 21933415
2019 The triglyceride synthesis enzymes DGAT1 and DGAT2 have distinct and overlapping functions in adipocytes. Journal of lipid research 138 30936184
2006 The lipogenic enzymes DGAT1, FAS, and LPL in adipose tissue: effects of obesity, insulin resistance, and TZD treatment. Journal of lipid research 135 16894240
2003 DGAT1, a new positional and functional candidate gene for intramuscular fat deposition in cattle. Animal genetics 124 14510671
2005 Increased very low density lipoprotein secretion and gonadal fat mass in mice overexpressing liver DGAT1. The Journal of biological chemistry 119 15797871
2003 Effects of DGAT1 variants on milk production traits in German cattle breeds. Journal of animal science 119 12926772
2010 Topological orientation of acyl-CoA:diacylglycerol acyltransferase-1 (DGAT1) and identification of a putative active site histidine and the role of the n terminus in dimer/tetramer formation. The Journal of biological chemistry 118 20876538
2022 Chenodeoxycholic acid suppresses AML progression through promoting lipid peroxidation via ROS/p38 MAPK/DGAT1 pathway and inhibiting M2 macrophage polarization. Redox biology 117 36084349
2010 A distinct DGAT with sn-3 acetyltransferase activity that synthesizes unusual, reduced-viscosity oils in Euonymus and transgenic seeds. Proceedings of the National Academy of Sciences of the United States of America 98 20439724
2002 Characterization of the DGAT1 gene in the New Zealand dairy population. Journal of dairy science 98 12512625
2011 ABI4 activates DGAT1 expression in Arabidopsis seedlings during nitrogen deficiency. Plant physiology 94 21515696
2012 The use of stable isotope-labeled glycerol and oleic acid to differentiate the hepatic functions of DGAT1 and -2. Journal of lipid research 93 22493088
2018 Intestinal Failure and Aberrant Lipid Metabolism in Patients With DGAT1 Deficiency. Gastroenterology 92 29604290
2010 DGAT1 inhibitors as anti-obesity and anti-diabetic agents. Current opinion in drug discovery & development 90 20597032
2014 Palmitic acid and DGAT1 deficiency enhance osteoclastogenesis, while oleic acid-induced triglyceride formation prevents it. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 85 24272998
2014 Cardiomyocyte-specific loss of diacylglycerol acyltransferase 1 (DGAT1) reproduces the abnormalities in lipids found in severe heart failure. The Journal of biological chemistry 70 25157099
2011 DGAT1 deficiency decreases PPAR expression and does not lead to lipotoxicity in cardiac and skeletal muscle. Journal of lipid research 69 21205704
2013 ABA-insensitive (ABI) 4 and ABI5 synergistically regulate DGAT1 expression in Arabidopsis seedlings under stress. FEBS letters 68 23942253
2010 Intestine-specific expression of acyl CoA:diacylglycerol acyltransferase 1 reverses resistance to diet-induced hepatic steatosis and obesity in Dgat1-/- mice. Journal of lipid research 66 20147738
2012 Effects of DGAT1 gene on meat and carcass fatness quality in Chinese commercial cattle. Molecular biology reports 61 23143182
2004 DGAT1 polymorphism in Bos indicus and Bos taurus cattle breeds. The Journal of dairy research 60 15190946
2021 Hypoxia-inducible lipid droplet-associated induces DGAT1 and promotes lipid storage in hepatocytes. Molecular metabolism 58 33465519
2018 The MYB96 Transcription Factor Regulates Triacylglycerol Accumulation by Activating DGAT1 and PDAT1 Expression in Arabidopsis Seeds. Plant & cell physiology 57 29660088
2012 Intestinal DGAT1 deficiency reduces postprandial triglyceride and retinyl ester excursions by inhibiting chylomicron secretion and delaying gastric emptying. Journal of lipid research 57 22911105
2013 Activities of acyl-CoA:diacylglycerol acyltransferase (DGAT) and phospholipid:diacylglycerol acyltransferase (PDAT) in microsomal preparations of developing sunflower and safflower seeds. Planta 56 23539042
2009 Role of MGAT2 and DGAT1 in the release of gut peptides after triglyceride ingestion. Biochemical and biophysical research communications 55 19732742
2004 The role of acyl-CoA:diacylglycerol acyltransferase (DGAT) in energy metabolism. Annals of medicine 55 15224651
2020 Oil-Producing Metabolons Containing DGAT1 Use Separate Substrate Pools from those Containing DGAT2 or PDAT. Plant physiology 52 32732347
2021 SARS-CoV-2 exploits host DGAT and ADRP for efficient replication. Cell discovery 47 34702802
2022 An oncogenic JMJD6-DGAT1 axis tunes the epigenetic regulation of lipid droplet formation in clear cell renal cell carcinoma. Molecular cell 46 35764091
2017 Identification and characterization of a novel DGAT1 missense mutation associated with congenital diarrhea. Journal of lipid research 46 28373485
2004 The DGAT1 K232A mutation is not solely responsible for the milk production quantitative trait locus on the bovine chromosome 14. Journal of dairy science 45 14762086
2004 Development of the mammary gland requires DGAT1 expression in stromal and epithelial tissues. Development (Cambridge, England) 45 15163627
2022 Oxidative stress from DGAT1 oncoprotein inhibition in melanoma suppresses tumor growth when ROS defenses are also breached. Cell reports 43 35732120
2016 Effects of the diacylglycerol o-acyltransferase 1 (DGAT1) K232A polymorphism on fatty acid, protein, and mineral composition of dairy cattle milk. Journal of dairy science 43 26898284
2004 Inhibitory activity of diacylglycerol acyltransferase (DGAT) and microsomal triglyceride transfer protein (MTP) by the flavonoid, taxifolin, in HepG2 cells: potential role in the regulation of apolipoprotein B secretion. Atherosclerosis 43 15380446
2012 Deficiency of the lipid synthesis enzyme, DGAT1, extends longevity in mice. Aging 42 22291164
2024 The role of DGAT1 and DGAT2 in regulating tumor cell growth and their potential clinical implications. Journal of translational medicine 40 38500157
2016 Congenital protein losing enteropathy: an inborn error of lipid metabolism due to DGAT1 mutations. European journal of human genetics : EJHG 40 26883093
2021 Association of DGAT1 With Cattle, Buffalo, Goat, and Sheep Milk and Meat Production Traits. Frontiers in veterinary science 38 34485439
2004 DGAT1 overexpression in muscle by in vivo DNA electroporation increases intramyocellular lipid content. Journal of lipid research 38 15576838
2016 ATGL and DGAT1 are involved in the turnover of newly synthesized triacylglycerols in hepatic stellate cells. Journal of lipid research 37 27179362
2014 Therapeutic strategies for metabolic diseases: Small-molecule diacylglycerol acyltransferase (DGAT) inhibitors. ChemMedChem 36 24954424
2017 Ghrelin deletion protects against age-associated hepatic steatosis by downregulating the C/EBPα-p300/DGAT1 pathway. Aging cell 35 29024407
2004 New Polyacetylenes, DGAT inhibitors from the roots of Panax ginseng. Planta medica 34 15114494
2015 Effects of the DGAT1 polymorphism on test-day milk production traits throughout lactation. Journal of dairy science 32 26142855
2013 Association of polymorphisms at DGAT1, leptin, SCD1, CAPN1 and CAST genes with color, marbling and water holding capacity in meat from beef cattle populations in Sweden. Meat science 30 23501244
2006 Characterization of the DGAT1 mutations and the CSN1S1 promoter in the German Angeln dairy cattle population. Journal of dairy science 30 16840633
2006 DGAT1 and ABCG2 polymorphism in Indian cattle (Bos indicus) and buffalo (Bubalus bubalis) breeds. BMC veterinary research 29 17087837
2004 Up-regulation of hepatic Acyl CoA: Diacylglycerol acyltransferase-1 (DGAT-1) expression in nephrotic syndrome. Kidney international 29 15200432
2017 Identification and characterization of an efficient acyl-CoA: diacylglycerol acyltransferase 1 (DGAT1) gene from the microalga Chlorella ellipsoidea. BMC plant biology 28 28222675
2009 Effects of DGAT1 and GHR on milk yield and milk composition in the Chinese dairy population. Animal genetics 28 19781040
2020 Genome-wide identification of Diacylglycerol Acyltransferases (DGAT) family genes influencing Milk production in Buffalo. BMC genetics 27 32138658
2019 In silico design of diacylglycerol acyltransferase-1 (DGAT1) inhibitors based on SMILES descriptors using Monte-Carlo method. SAR and QSAR in environmental research 27 31331203
2021 Ectopic overexpression of a type-II DGAT (CeDGAT2-2) derived from oil-rich tuber of Cyperus esculentus enhances accumulation of oil and oleic acid in tobacco leaves. Biotechnology for biofuels 26 33757551
2021 Loss of ephrin B2 receptor (EPHB2) sets lipid rheostat by regulating proteins DGAT1 and ATGL inducing lipid droplet storage in prostate cancer cells. Laboratory investigation; a journal of technical methods and pathology 25 33824421
2009 Comparative genomics and proteomics of vertebrate diacylglycerol acyltransferase (DGAT), acyl CoA wax alcohol acyltransferase (AWAT) and monoacylglycerol acyltransferase (MGAT). Comparative biochemistry and physiology. Part D, Genomics & proteomics 25 20374941
2023 DGKB mediates radioresistance by regulating DGAT1-dependent lipotoxicity in glioblastoma. Cell reports. Medicine 24 36603576
2021 Up-regulation of DGAT1 in cancer tissues and tumor-infiltrating macrophages influenced survival of patients with gastric cancer. BMC cancer 24 33750350
2015 Effect of the DGAT1 K232A genotype of dairy cows on the milk metabolome and proteome. Journal of dairy science 23 25771043
2011 DGAT1, GH, GHR, PRL and PRLR polymorphism in water buffalo (Bubalus bubalis). Reproduction in domestic animals = Zuchthygiene 23 21883511
2006 Effects of DGAT1 deficiency on energy and glucose metabolism are independent of adiponectin. American journal of physiology. Endocrinology and metabolism 23 16595853
2020 Functional Characterization of Three Novel Genes Encoding Diacylglycerol Acyltransferase (DGAT) from Oil-Rich Tubers of Cyperus esculentus. Plant & cell physiology 22 31532486
2013 Aphadilactones A-D, four diterpenoid dimers with DGAT inhibitory and antimalarial activities from a Meliaceae plant. The Journal of organic chemistry 22 24344740
2020 Differential actions of diacylglycerol acyltransferase (DGAT) 1 and 2 in regulating lipid metabolism and progesterone secretion of goose granulosa cells. The Journal of steroid biochemistry and molecular biology 21 32565248
2014 Discovery of a Potent and Selective DGAT1 Inhibitor with a Piperidinyl-oxy-cyclohexanecarboxylic Acid Moiety. ACS medicinal chemistry letters 21 25349648
2014 Intestine-targeted DGAT1 inhibition improves obesity and insulin resistance without skin aberrations in mice. PloS one 21 25405858
2003 DGAT: novel therapeutic target for obesity and type 2 diabetes mellitus. Current drug targets. Immune, endocrine and metabolic disorders 21 14683457
2023 Prevention of lipid droplet accumulation by DGAT1 inhibition ameliorates sepsis-induced liver injury and inflammation. JHEP reports : innovation in hepatology 20 38293685
2022 Role of diacylglycerol O-acyltransferase (DGAT) isoforms in bovine hepatic fatty acid metabolism. Journal of dairy science 20 35181144
2019 Significant genetic effects of JAK2 and DGAT1 mutations on milk fat content and mastitis resistance in Holsteins. The Journal of dairy research 20 31779717
2019 DGAT1 inhibits retinol-dependent regulatory T cell formation and mediates autoimmune encephalomyelitis. Proceedings of the National Academy of Sciences of the United States of America 19 30718413
2019 DGAT2 partially compensates for lipid-induced ER stress in human DGAT1-deficient intestinal stem cells. Journal of lipid research 19 31315900
2015 Phosphorylation and function of DGAT1 in skeletal muscle cells. Biophysics reports 19 26942218
2014 Deconstructing the DGAT1 enzyme: Binding sites and substrate interactions. Biochimica et biophysica acta 19 25152299
2009 Cloning and molecular characterization of the acyl-CoA: diacylglycerol acyltransferase 1 (DGAT1) gene from Echium. Lipids 19 19412626
2008 Effect of CLA and other C18 unsaturated fatty acids on DGAT in bovine milk fat biosynthetic systems. Lipids 19 18704537
2024 Lipotoxicity of palmitic acid is associated with DGAT1 downregulation and abolished by PPARα activation in liver cells. Journal of lipid research 18 39505261
2023 Transmembrane Protein 68 Functions as an MGAT and DGAT Enzyme for Triacylglycerol Biosynthesis. International journal of molecular sciences 18 36768334
2016 Novel role of a triglyceride-synthesizing enzyme: DGAT1 at the crossroad between triglyceride and cholesterol metabolism. Biochimica et biophysica acta 18 27344248
2014 Characterisation of DGAT1 and DGAT2 from Jatropha curcas and their functions in storage lipid biosynthesis. Functional plant biology : FPB 18 32480992
2024 Glycerol Kinase Drives Hepatic de novo Lipogenesis and Triglyceride Synthesis in Nonalcoholic Fatty Liver by Activating SREBP-1c Transcription, Upregulating DGAT1/2 Expression, and Promoting Glycerol Metabolism. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 17 39418169
2018 Hepatic VLDL secretion: DGAT1 determines particle size but not particle number, which can be supported entirely by DGAT2. Journal of lipid research 17 30397187
2013 Defining the key pharmacophore elements of PF-04620110: discovery of a potent, orally-active, neutral DGAT-1 inhibitor. Bioorganic & medicinal chemistry 17 23871442
2007 Molecular cloning and single nucleotide polymorphism detection of buffalo DGAT1 gene. Biochemical genetics 17 17592768
2014 The utilization of the acyl-CoA and the involvement PDAT and DGAT in the biosynthesis of erucic acid-rich triacylglycerols in Crambe seed oil. Lipids 14 24578031