Affinage

ELOVL6

Very long chain fatty acid elongase 6 · UniProt Q9H5J4

Length
265 aa
Mass
31.4 kDa
Annotated
2026-04-28
83 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ELOVL6 is a microsomal fatty acid elongase that serves as the sole enzyme converting palmitate (C16:0) to stearate (C18:0) in vivo, thereby controlling the C16-to-C18 ratio of saturated and monounsaturated fatty acids and shaping the composition of downstream lipid species including ceramides, sphingolipids, and phospholipids (PMID:17906635, PMID:25281760). Transcriptionally regulated by SREBP-1c through sterol regulatory elements in its promoter (PMID:18226595, PMID:33685712) and post-translationally activated by physical interaction with the 3-ketoacyl-CoA reductase KAR (PMID:25003994), ELOVL6 activity determines membrane lipid composition that in turn modulates insulin signaling via IRS-2/PKCε/Akt (PMID:17906635), ER stress through IRE1/PERK pathways and ceramide generation (PMID:21266672, PMID:30081392, PMID:33821992), NLRP3 inflammasome activation (PMID:22753171), and mitochondrial oxidative phosphorylation (PMID:26628376, PMID:40835210). By governing fatty acid chain length, ELOVL6 broadly influences metabolic homeostasis, inflammatory responses, and cell fate decisions—including vascular smooth muscle phenotypic switching via ROS/AMPK/KLF4 (PMID:27881420), macrophage cholesterol efflux and repair phenotypes (PMID:21817094, PMID:37669365), phospholipid-dependent KRAS-G12V membrane association and stability (PMID:40954224), and membrane rigidity controlling pinocytosis in pancreatic cancer (PMID:39956817).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2007 High

    Establishing the core enzymatic function of ELOVL6 and its metabolic significance: the foundational question of which elongase converts C16:0 to C18:0 was resolved, revealing that ELOVL6 loss protects against obesity-induced insulin resistance by modulating hepatic PKCε/IRS-2/Akt signaling.

    Evidence Elovl6 knockout mouse on high-fat diet and ob/ob background with hepatic fatty acid profiling and insulin signaling readouts

    PMID:17906635

    Open questions at the time
    • Substrate specificity among other chain lengths and unsaturated species not fully delineated
    • Whether protection from insulin resistance is cell-autonomous in hepatocytes versus systemic
    • Mechanism linking altered C16/C18 ratio to PKCε activity not defined
  2. 2008 High

    Identifying the transcriptional control of ELOVL6 resolved how lipogenic signals converge on fatty acid elongation: SREBP-1c directly binds SRE elements in the Elovl6 promoter, placing ELOVL6 under the canonical lipogenic transcriptional program.

    Evidence Luciferase reporter, EMSA, ChIP, and adenoviral RNAi of SREBP-1 in mouse liver

    PMID:18226595

    Open questions at the time
    • Contribution of other transcription factors (e.g., LXR, ChREBP) to ELOVL6 regulation not addressed
    • Post-transcriptional regulation mechanisms unknown at this point
  3. 2009 Medium

    A selective radioligand binding study provided the first pharmacological and mechanistic insight into the ELOVL6 active site, revealing that inhibitor binding requires the palmitoyl-CoA-bound enzyme state, consistent with an acyl-enzyme intermediate.

    Evidence Radioligand binding assay with palmitoyl-CoA dependence and selectivity profiling against ELOVL family members

    PMID:19505953

    Open questions at the time
    • No structural model of the ELOVL6 active site or inhibitor binding mode
    • In vivo efficacy of selective inhibitors not demonstrated
  4. 2011 High

    Two studies demonstrated that ELOVL6 activity governs lipotoxic ER stress and cell death across distinct cell types: in β-cells, ELOVL6 drives palmitate-to-stearate conversion causing ER stress and apoptosis, while in macrophages ELOVL6 modulates cholesterol efflux and atherosclerotic lesion formation through altered esterified cholesterol fatty acid composition.

    Evidence siRNA knockdown and overexpression with radiolabeled fatty acid tracking in INS-1 cells; bone marrow transplantation of Elovl6−/− cells into LDLR−/− mice with cholesterol efflux assays

    PMID:21266672 PMID:21817094

    Open questions at the time
    • Specific lipid species (ceramides, phospholipids) mediating ER stress in β-cells not identified
    • Whether macrophage effects are through membrane composition or signaling lipids unclear
  5. 2012 High

    ELOVL6 was positioned upstream of NLRP3 inflammasome activation, connecting fatty acid elongation to innate immune inflammatory signaling in the liver and establishing a mechanistic basis for ELOVL6's role in NASH pathogenesis.

    Evidence Elovl6 loss- and gain-of-function mouse models with NLRP3 inflammasome activation assays; human NASH liver samples

    PMID:22753171

    Open questions at the time
    • Direct lipid species triggering NLRP3 activation not identified
    • Whether ELOVL6-NLRP3 axis operates in non-hepatic tissues unknown
  6. 2014 High

    Three advances refined the biochemical understanding of ELOVL6: definitive in vivo substrate specificity was established (C16:0→C18:0 is ELOVL6-specific; C16:1n-7→C18:1n-7 is not), KAR was identified as a physical and functional activator of ELOVL6 through both conformational and catalytic mechanisms, and ELOVL6 deficiency was shown to improve β-cell function via altered islet ATP/ADP ratios.

    Evidence KO mouse lipidomics confirming substrate specificity; in vitro reconstitution with purified ELOVL6 and KAR mutants; islet isolation and GSIS assays from Elovl6−/− mice

    PMID:24938128 PMID:25003994 PMID:25281760

    Open questions at the time
    • Crystal structure of ELOVL6-KAR complex not available
    • Whether KAR interaction is specific to ELOVL6 or shared with other ELOVLs unknown
    • Mechanism linking fatty acid composition to ATP/ADP ratio in islets not resolved
  7. 2015 High

    ELOVL6 was shown to be essential for brown adipose tissue thermogenic function, linking fatty acid elongation to mitochondrial electron transport chain integrity and revealing compensatory white adipose tissue beiging in its absence.

    Evidence Elovl6 KO mice under cold exposure with BAT ETC component expression and oxygen consumption measurements

    PMID:26628376

    Open questions at the time
    • Which specific lipid species are required for ETC complex assembly or function not defined
    • Whether BAT-specific ELOVL6 deletion recapitulates the phenotype unknown
  8. 2016 High

    ELOVL6 was connected to vascular smooth muscle cell phenotypic switching through a defined ROS→AMPK→KLF4 pathway, and separately to chondrocyte growth plate biology through altered transcription factor localization, broadening the known tissue contexts of ELOVL6 function.

    Evidence Elovl6−/− wire-injury model and VSMC siRNA with KLF4 epistasis; Elovl6 KO mouse skeletal analysis with chondrocyte knockdown

    PMID:27467521 PMID:27881420

    Open questions at the time
    • How altered fatty acid composition generates ROS in VSMCs is mechanistically undefined
    • Direct lipid mediators affecting HDAC4/5/7 localization in chondrocytes not identified
  9. 2017 High

    Oleate (C18:1n-9) was identified as a key lipotoxic mediator downstream of ELOVL6 in pancreatic islets: Elovl6 deletion in diabetic db/db mice preserved β-cell mass by preventing oleate accumulation and associated ER stress, inflammation, and apoptosis.

    Evidence Elovl6 deletion in db/db mice; β-cell mass morphometry; ex vivo oleate treatment of isolated islets with GSIS and ER stress assays

    PMID:28461456

    Open questions at the time
    • Whether oleate toxicity is direct or requires incorporation into ceramides/phospholipids unclear
    • Relevance to human β-cell lipotoxicity not confirmed
  10. 2018 Medium

    Studies in Drosophila and mouse keratinocytes extended ELOVL6's ER stress role across species and revealed tissue-specific consequences: loss of the Drosophila ortholog Baldspot rescued retinal degeneration by reducing IRE1/PERK signaling (rescued by dietary stearate), while in murine skin ELOVL6 deficiency caused cis-vaccenic acid accumulation driving DAMP release and proinflammatory responses.

    Evidence Drosophila Baldspot KO with Rh1G69D ER stress model and dietary stearate rescue; Elovl6−/− mouse tape-stripping model with epidermal lipidomics and DAMP measurement

    PMID:30081392 PMID:30518914

    Open questions at the time
    • How stearate specifically alleviates ER stress at the molecular level not defined
    • Whether cis-vaccenic acid directly triggers cell death or acts through membrane perturbation unknown
  11. 2021 High

    ELOVL6 was placed within ceramide-dependent drug sensitivity and ferroptosis pathways: ELOVL6-dependent ceramide species are required for bortezomib-induced ER stress and cell death in myeloma, while ELOVL6 physically interacts with ACSL4 to modulate ferroptotic signaling in colorectal cancer; additionally, SREBP1 regulation of ELOVL6 through SRE elements was confirmed in a non-rodent mammalian system.

    Evidence ELOVL6 knockdown/overexpression in myeloma cells with lipidomics and xenograft; Co-IP of ELOVL6-ACSL4 with ferroptosis assays in HCT116 cells; ChIP and promoter mutagenesis in goat mammary epithelial cells

    PMID:33603479 PMID:33685712 PMID:33821992

    Open questions at the time
    • ACSL4 interaction confirmed by single Co-IP only, no reciprocal validation
    • Specific ceramide species mediating BTZ sensitivity not individually tested
    • Whether ELOVL6-ACSL4 interaction is direct or mediated through a lipid intermediate unknown
  12. 2022 High

    ELOVL6 was positioned upstream of the ceramide–sphingosine-1-phosphate biosynthesis axis in airway immunity: Elovl6 deficiency aggravated allergic inflammation through elevated palmitic acid, ceramides, and S1P, which could be pharmacologically reversed by ceramide synthase or sphingosine kinase inhibitors.

    Evidence Elovl6−/− mouse ovalbumin and HDM asthma models with lung lipidomics and pharmacological epistasis

    PMID:36592705

    Open questions at the time
    • Whether this ceramide-S1P axis operates similarly in other mucosal tissues unknown
    • Cell-type specificity (epithelial vs. immune) of ELOVL6 function in airway inflammation not resolved
  13. 2023 High

    ELOVL6 was shown to control macrophage inflammatory-to-reparative phenotype switching via S1P/PPARγ signaling, enhancing ABCA1-mediated lipid efflux and neurotrophic factor production, with functional consequences for demyelination and remyelination in neuroinflammatory disease models.

    Evidence Elovl6−/− macrophages with myelin phagocytosis, S1P/PPARγ pathway analysis, organotypic brain slices, and cuprizone mouse model

    PMID:37669365

    Open questions at the time
    • Whether ELOVL6 modulation in microglia versus infiltrating macrophages produces distinct effects unknown
    • Therapeutic window and specificity of ELOVL6 targeting in neuroinflammation not defined
  14. 2025 High

    ELOVL6 was identified as a critical regulator of membrane phospholipid composition with direct consequences for oncogenic signaling: c-MYC-driven ELOVL6 upregulation in PDAC alters membrane rigidity and pinocytosis; ELOVL6 controls phosphatidylethanolamine levels required for mitochondrial OXPHOS in bladder cancer; and a genome-wide CRISPR screen identified ELOVL6 as essential for KRAS-G12V membrane association and protein stability through phospholipid production.

    Evidence PDAC mouse models with membrane property measurements; ELOVL6 siRNA in bladder cancer cells with lipidomics and mitochondrial assays; genome-wide CRISPR KO screen with phospholipidomics and KRAS protein degradation assays

    PMID:39956817 PMID:40835210 PMID:40954224

    Open questions at the time
    • Specific phospholipid species required for KRAS-G12V membrane anchoring not individually defined
    • Whether ELOVL6 inhibition selectively targets mutant KRAS over wild-type KRAS in vivo unknown
    • Structural basis for how altered phospholipid composition affects membrane protein stability not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key remaining questions include the structural basis of ELOVL6 catalysis and its interaction with KAR, the identity of specific lipid species mediating ELOVL6-dependent signaling in each tissue context, and whether ELOVL6 inhibition can be therapeutically exploited with acceptable metabolic safety.
  • No crystal or cryo-EM structure of ELOVL6 or ELOVL6-KAR complex
  • Tissue-specific and cell-type-specific contributions of ELOVL6 not dissected with conditional knockouts in most contexts
  • Therapeutic index of ELOVL6 inhibition across metabolic, inflammatory, and oncologic settings not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0008289 lipid binding 2
Localization
GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3
Partners
ACSL4KARSREBP1

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 ELOVL6 is the elongase that catalyzes the conversion of palmitate (C16:0) to stearate (C18:0); deletion of Elovl6 in mice causes accumulation of C16 fatty acids and loss of C18 species. Loss of Elovl6 protects against obesity-induced insulin resistance by restoring hepatic insulin receptor substrate-2 (IRS-2) and suppressing hepatic protein kinase C epsilon (PKCε) activity, thereby restoring Akt phosphorylation. Elovl6 knockout mouse model; high-fat diet and ob/ob cross; measurement of hepatic fatty acid composition, IRS-2, PKCε activity, and Akt phosphorylation Nature medicine High 17906635
2008 The mouse Elovl6 gene promoter is a direct transcriptional target of SREBP-1c; two sterol regulatory elements (SRE-1 and SRE-2) in the promoter bind SREBP, with SRE-1 having higher affinity; adenoviral RNAi knockdown of SREBP-1 in mouse liver suppresses Elovl6 mRNA. Luciferase reporter assay; EMSA; chromatin immunoprecipitation (ChIP); adenoviral RNAi in mouse liver Biochemical and biophysical research communications High 18226595
2011 ELOVL6 is a microsomal enzyme elongating C12–C16 saturated and monounsaturated fatty acids; in pancreatic β-cells, Elovl6 knockdown limits palmitate elongation to stearate and increases palmitoleate production, attenuating palmitate-induced ER stress and apoptosis; conversely, Elovl6 overexpression increases palmitate elongation to stearate and enhances ER stress and apoptosis. siRNA knockdown and overexpression in INS-1 β-cells; fatty acid radiolabeling to track elongation; measurement of ER stress markers and apoptosis American journal of physiology. Endocrinology and metabolism High 21266672
2011 Macrophage-specific Elovl6 deficiency reduces foam cell formation by increasing cholesterol efflux and expression of cholesterol efflux transporters; absence of Elovl6 decreases n-6 polyunsaturated fatty acids in the esterified cholesterol fraction of macrophages; bone marrow transplantation of Elovl6-/- cells into LDL-R-/- mice reduces atherosclerotic lesion area. Bone marrow transplantation into LDL-R-/- mice; peritoneal macrophage isolation; acetylated-LDL uptake and cholesterol efflux assays; fatty acid composition analysis Arteriosclerosis, thrombosis, and vascular biology High 21817094
2012 Elovl6 promotes nonalcoholic steatohepatitis (NASH); deletion of Elovl6 reduces palmitate-induced activation of the NLRP3 inflammasome, which is a mechanistic basis for Elovl6-mediated modulation of hepatic inflammation, oxidative stress, and fibrosis. Elovl6 loss- and gain-of-function mouse models; NLRP3 inflammasome activation assays; human NASH liver samples for correlation Hepatology (Baltimore, Md.) High 22753171
2013 Elovl6 is a rate-limiting enzyme for elongation of saturated and monounsaturated fatty acids; its deficiency in mice causes derangement of fatty acid profile and leads to severe fibroproliferative response after bleomycin-induced lung injury; Elovl6 knockdown induces apoptosis, TGF-β1 expression, and reactive oxygen species generation in alveolar type II epithelial cells. Elovl6-/- mouse model with intratracheal bleomycin; siRNA knockdown in lung epithelial cells; measurement of apoptosis, TGF-β1, and ROS Nature communications High 24113622
2014 ELOVL6 is the only enzyme capable of elongating palmitate (C16:0) to stearate (C18:0) in vivo; Elovl6-/- mouse livers accumulate C16:0 and C16:1 n-7 with loss of C18:0 and C18:1 n-9, confirming substrate specificity. Palmitoleate (C16:1 n-7) to vaccenate (C18:1 n-7) elongation was not specific to ELOVL6. Elovl6 knockout mouse generation; hepatic fatty acid composition analysis by mass spectrometry; dietary intervention studies Journal of lipid research High 25281760
2014 ELOVL6 activity regulates fatty acid composition in pancreatic islets; in Elovl6-/- mice fed a high-fat/high-sucrose diet, improved glucose-stimulated insulin secretion (GSIS) is associated with increased islet ATP/ADP ratio and suppression of ATF-3 expression. Elovl6-/- mouse model; high-fat/high-sucrose diet; isolated islet glucose-stimulated insulin secretion assay; ATP/ADP ratio measurement; ATF-3 expression analysis Biochemical and biophysical research communications Medium 24938128
2014 ELOVL6 enzymatic activity is regulated by the 3-ketoacyl-CoA reductase KAR via two modes: (1) KAR induces conformational changes in ELOVL6 independent of KAR enzyme activity, enhancing ELOVL6 activity ~3-fold; (2) KAR enzyme activity-dependent conversion of 3-ketoacyl-CoA to 3-hydroxyacyl-CoA facilitates product release from a presumed ELOVL6-KAR complex, further enhancing activity ~10-fold in the presence of NADPH. In vitro fatty acid elongation assay using membrane fractions; purified ELOVL6; KAR mutants; NADPH-dependence experiments PloS one High 25003994
2015 Elovl6 is necessary for thermogenic function of brown adipose tissue (BAT); loss of Elovl6 causes reduced expression of mitochondrial electron transport chain components and lower BAT thermogenic capacity without altering classical BAT markers; this is compensated by increased beiging of subcutaneous white adipose tissue. Elovl6 KO mice; cold exposure experiments; mitochondrial ETC component expression; BAT oxygen consumption; thermoneutrality and aging studies Cell reports High 26628376
2016 Elovl6 inhibition in vascular smooth muscle cells (VSMCs) causes increased palmitate and reduced oleate levels, leading to ROS production, AMPK activation, induction of KLF4 (a pluripotency gene), and phenotypic switching of VSMCs including growth arrest and downregulation of VSMC markers; KLF4 knockdown attenuates AMPK-induced phenotypic switching, establishing KLF4 as a bona fide AMPK target in this pathway. Elovl6-/- mouse neointima wire-injury model; siRNA knockdown in cultured VSMCs; PDGF-BB stimulation; ROS measurement; AMPK and mTOR phosphorylation; KLF4 knockdown epistasis Journal of the American Heart Association High 27881420
2016 Elovl6 plays a critical role in chondrocyte growth and differentiation during growth plate development; Elovl6-/- mice show reduced chondrocyte proliferation and accelerated hypertrophic differentiation, associated with increased Collagen10α1 expression and elevated Foxa2/a3 and Mef2c mRNA; increased nuclear Foxa2 and cytoplasmic HDAC4/5/7 protein levels are observed in Elovl6 knockdown chondrocytes. Elovl6 KO mouse skeletal analysis; histology; gene expression; siRNA knockdown in chondrocyte cell lines; protein localization by fractionation PloS one Medium 27467521
2017 Elovl6 deletion in db/db mice markedly increases β-cell mass with increased proliferation and decreased apoptosis; Elovl6 deletion suppresses oleate (C18:1n-9) elevation in islets, cell stress, and inflammation; isolated Elovl6-/- islets show reduced susceptibility to palmitate-induced ER stress, inflammation, and β-cell apoptosis; oleate-treated islets impair glucose-stimulated insulin secretion regardless of Elovl6 genotype, implicating oleate as a key lipotoxic mediator. Elovl6 deletion in db/db mouse model; β-cell mass morphometry; islet isolation; ex vivo palmitate and oleate treatment; ER stress markers; GSIS assay Diabetes High 28461456
2018 Elovl6 in keratinocytes regulates fatty acid composition; Elovl6-/- mice have higher levels of cis-vaccenic acid (CVA) in the epidermis; CVA accelerates tape stripping-triggered keratinocyte death and release of DAMPs (HMGB-1 and IL-1α), which induce proinflammatory cytokine and chemokine production (IL-1β, CXCL-1). Elovl6-/- mouse tape-stripping model; epidermal fatty acid composition analysis; DAMP measurement; cytokine/chemokine quantification Cell death & disease Medium 30518914
2018 In a Drosophila model (Baldspot/ELOVL6 ortholog), loss of Baldspot rescues retinal degeneration in a model of ER stress (Rh1G69D) and reduces IRE1 and PERK signaling and cell death; dietary supplementation with stearate bypasses the need for Baldspot activity, linking the enzyme's conversion of C16 to C18 to ER stress modulation. Drosophila Baldspot knockout; Rh1G69D ER stress model; IRE1 and PERK signaling assays; dietary stearate supplementation rescue PLoS genetics Medium 30081392
2021 ELOVL6 directly interacts with ACSL4 (a key regulator of ferroptosis), as confirmed by co-immunoprecipitation; ELOVL6 overexpression in colorectal cancer HCT116 cells reverses apatinib-induced ferroptosis, indicating ELOVL6 acts upstream of ACSL4-mediated ferroptotic signaling. Co-immunoprecipitation; ELOVL6 overexpression; CCK-8 cell viability; ROS and iron measurement; Western blot for ferroptosis markers Cancer management and research Medium 33603479
2021 ELOVL6 levels regulate bortezomib (BTZ) sensitivity in multiple myeloma cells; ELOVL6 depletion suppresses BTZ-induced ER stress and cytotoxicity; restoration of ELOVL6 in BTZ-resistant cells resensitizes them to BTZ via upregulation of ELOVL6-dependent ceramide species, which are required for BTZ-induced ER stress and cell death. ELOVL6 knockdown and overexpression in MM cell lines; BTZ treatment; lipidomic profiling; ceramide measurement; xenograft plasmacytoma mouse model Blood advances High 33821992
2022 ELOVL6 deficiency in mice aggravates allergic airway inflammation; lipidomic profiling revealed elevated palmitic acid, ceramides, and sphingosine-1-phosphate (S1P) in Elovl6-/- mouse lungs after sensitization; treatment with inhibitors of ceramide synthase (fumonisin B1) or sphingosine kinase (DL-threo-dihydrosphingosine) ameliorated the aggravated inflammation, placing ELOVL6 upstream of the ceramide-S1P biosynthesis pathway in airway immune regulation. Elovl6-/- mouse ovalbumin and house dust mite asthma models; lipidomic profiling; pharmacological inhibition of ceramide synthase and sphingosine kinase; cellular immunology assays The Journal of allergy and clinical immunology High 36592705
2023 ELOVL6 is upregulated in myelin-phagocytosing macrophages and in MS lesions; Elovl6 depletion induces a repair-promoting phagocyte phenotype through activation of the S1P/PPARγ pathway, enhances ABCA1-mediated lipid efflux, increases neurotrophic factor production, and reduces inflammatory mediator expression; Elovl6 deficiency prevented demyelination and boosted remyelination in organotypic brain slice cultures and the cuprizone mouse model. In vitro myelin phagocytosis model; Elovl6-/- macrophages; S1P/PPARγ pathway analysis; ABCA1-mediated cholesterol efflux assay; organotypic brain slice cultures; cuprizone mouse model Proceedings of the National Academy of Sciences of the United States of America High 37669365
2023 miR-135b-5p, miR-135a-5p, miR-125a-5p, miR-125b-5p, and miR-22-3p directly bind the 3'-UTR of human ELOVL6 mRNA and downregulate its expression; miR-135b-5p and miR-135a-5p suppress glioblastoma cell proliferation and migration by inhibiting ELOVL6 at both mRNA and protein levels. Dual-luciferase reporter assay with ELOVL6 3'-UTR; miRNA overexpression in glioblastoma cells; cell proliferation and migration assays; qRT-PCR and Western blot BBA advances Medium 37082255
2025 c-MYC directly upregulates ELOVL6 expression during pancreatic cancer (PDAC) tumor progression; genetic or chemical inhibition of ELOVL6 reduces proliferation and migration by altering fatty acid composition, affecting membrane rigidity, permeability, and pinocytosis; in vivo ELOVL6 inhibition suppresses tumor growth and improves Abraxane response. PDAC mouse models and cell lines; c-MYC overexpression/inhibition; ELOVL6 genetic knockdown and chemical inhibitor; fatty acid composition analysis; membrane property measurements; in vivo tumor growth and survival Nature communications High 39956817
2025 ELOVL6 controls phospholipid production exploited by KRAS-G12V for membrane association; CRISPR-Cas9 genome-wide knockout screen identified ELOVL6 as a selective modulator of KRAS-G12V protein expression; ELOVL6 attenuation induces degradation of KRAS-G12V protein through altered phospholipid composition, reducing aberrant oncogenic signaling. CRISPR-Cas9 genome-wide KO screen; ELOVL6 inhibition in KRAS-G12V cancer cells; phospholipidomics; KRAS protein expression and degradation assays Nature chemical biology High 40954224
2009 A selective radioligand ([(3)H]Compound-A) was identified for ELOVL6 that binds in a palmitoyl-CoA-dependent manner in the absence of malonyl-CoA and NADPH, suggesting Compound-A recognizes an enzyme-substrate (acyl-enzyme intermediate) complex; Compound-A inhibits human and mouse ELOVL6 with >100-fold selectivity over other ELOVL family members. Radioligand binding assay; enzyme inhibition assay; selectivity profiling against ELOVL family members; substrate-dependence studies Journal of biochemistry Medium 19505953
2025 ELOVL6 knockdown in FGFR3-mutant bladder cancer cells markedly reduces phosphatidylethanolamine levels, impairs mitochondrial complex I and II protein expression and mitochondrial oxidative phosphorylation (OXPHOS), and activates the ECM-integrin-FAK pathway as a compensatory response; these data establish that ELOVL6 regulates lipid composition to preserve mitochondrial function. ELOVL6 siRNA knockdown in BC cell lines; lipidomics; mitochondrial OXPHOS measurement; RNA sequencing; in vivo tumor growth Biochimica et biophysica acta. Molecular basis of disease Medium 40835210
2021 SREBP1 directly binds to SRE1 and SRE3 elements in the goat ELOVL6 promoter to regulate its transcription; mutation of both SRE sites abolishes SREBP1-stimulated and linoleic acid-repressed ELOVL6 promoter activity; chromatin immunoprecipitation confirmed in vivo SREBP1 binding at these sites in goat mammary epithelial cells. Promoter deletion analysis; site-directed mutagenesis; luciferase reporter assay; chromatin immunoprecipitation in goat mammary epithelial cells Journal of dairy science Medium 33685712

Source papers

Stage 0 corpus · 83 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Crucial role of a long-chain fatty acid elongase, Elovl6, in obesity-induced insulin resistance. Nature medicine 432 17906635
2009 Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nature genetics 362 19169255
2012 Elovl6 promotes nonalcoholic steatohepatitis. Hepatology (Baltimore, Md.) 156 22753171
2009 Elovl6: a new player in fatty acid metabolism and insulin sensitivity. Journal of molecular medicine (Berlin, Germany) 145 19259639
2013 Deranged fatty acid composition causes pulmonary fibrosis in Elovl6-deficient mice. Nature communications 99 24113622
1992 Isolation of cDNAs for LCE and HCE, two constituent proteases of the hatching enzyme of Oryzias latipes, and concurrent expression of their mRNAs during development. Developmental biology 95 1397682
2011 Modulation of palmitate-induced endoplasmic reticulum stress and apoptosis in pancreatic β-cells by stearoyl-CoA desaturase and Elovl6. American journal of physiology. Endocrinology and metabolism 94 21266672
2008 Mouse Elovl-6 promoter is an SREBP target. Biochemical and biophysical research communications 92 18226595
2011 Psoriasis risk genes of the late cornified envelope-3 group are distinctly expressed compared with genes of other LCE groups. The American journal of pathology 88 21435436
2014 Deletion of ELOVL6 blocks the synthesis of oleic acid but does not prevent the development of fatty liver or insulin resistance. Journal of lipid research 69 25281760
2021 Apatinib Promotes Ferroptosis in Colorectal Cancer Cells by Targeting ELOVL6/ACSL4 Signaling. Cancer management and research 68 33603479
2015 Brown Adipose Tissue Thermogenic Capacity Is Regulated by Elovl6. Cell reports 66 26628376
2017 Psoriasis-Associated Late Cornified Envelope (LCE) Proteins Have Antibacterial Activity. The Journal of investigative dermatology 63 28634035
1989 Isolation and some properties of low choriolytic enzyme (LCE), a component of the hatching enzyme of the teleost, Oryzias latipes. Journal of biochemistry 59 2656665
2013 Polymorphism in the ELOVL6 gene is associated with a major QTL effect on fatty acid composition in pigs. PloS one 53 23341976
2016 Elongation of Long-Chain Fatty Acid Family Member 6 (Elovl6)-Driven Fatty Acid Metabolism Regulates Vascular Smooth Muscle Cell Phenotype Through AMP-Activated Protein Kinase/Krüppel-Like Factor 4 (AMPK/KLF4) Signaling. Journal of the American Heart Association 50 27881420
2018 Elovl6 is a negative clinical predictor for liver cancer and knockdown of Elovl6 reduces murine liver cancer progression. Scientific reports 49 29700319
2012 Novel qualitative aspects of tissue fatty acids related to metabolic regulation: lessons from Elovl6 knockout. Progress in lipid research 43 22266797
2011 Macrophage Elovl6 deficiency ameliorates foam cell formation and reduces atherosclerosis in low-density lipoprotein receptor-deficient mice. Arteriosclerosis, thrombosis, and vascular biology 37 21817094
2017 Elovl6 Deficiency Improves Glycemic Control in Diabetic db/db Mice by Expanding β-Cell Mass and Increasing Insulin Secretory Capacity. Diabetes 36 28461456
2019 Effect of ELOVL6 on the lipid metabolism of bovine adipocytes. Genomics 35 31901374
2020 Role of fatty acid elongase Elovl6 in the regulation of energy metabolism and pathophysiological significance in diabetes. Diabetology international 33 33479581
2010 Variants in MHC, LCE and IL12B have epistatic effects on psoriasis risk in Chinese population. Journal of dermatological science 33 21208785
2015 Epigenetic regulation of the ELOVL6 gene is associated with a major QTL effect on fatty acid composition in pigs. Genetics, selection, evolution : GSE 32 25887840
2018 Elovl6 regulates mechanical damage-induced keratinocyte death and skin inflammation. Cell death & disease 31 30518914
2018 Liquid Crystal Elastomers-A Path to Biocompatible and Biodegradable 3D-LCE Scaffolds for Tissue Regeneration. Materials (Basel, Switzerland) 30 29510523
2015 Absence of Elovl6 attenuates steatohepatitis but promotes gallstone formation in a lithogenic diet-fed Ldlr(-/-) mouse model. Scientific reports 30 26619823
2011 ELOVL6 genetic variation is related to insulin sensitivity: a new candidate gene in energy metabolism. PloS one 26 21701577
2019 Molecular Cloning, Characterization, and Nutritional Regulation of Elovl6 in Large Yellow Croaker (Larimichthys crocea). International journal of molecular sciences 25 30979053
2021 The fatty acid elongase ELOVL6 regulates bortezomib resistance in multiple myeloma. Blood advances 24 33821992
2013 The effect of LXRα, ChREBP and Elovl6 in liver and white adipose tissue on medium- and long-chain fatty acid diet-induced insulin resistance. Diabetes research and clinical practice 24 24262945
2023 Fatty acid elongation by ELOVL6 hampers remyelination by promoting inflammatory foam cell formation during demyelination. Proceedings of the National Academy of Sciences of the United States of America 23 37669365
2014 Two modes of regulation of the fatty acid elongase ELOVL6 by the 3-ketoacyl-CoA reductase KAR in the fatty acid elongation cycle. PloS one 22 25003994
2017 Hepatic ELOVL6 mRNA is regulated by the gga-miR-22-3p in egg-laying hen. Gene 21 28445717
2020 Estrogen Abolishes the Repression Role of gga-miR-221-5p Targeting ELOVL6 and SQLE to Promote Lipid Synthesis in Chicken Liver. International journal of molecular sciences 20 32120850
2018 Baldspot/ELOVL6 is a conserved modifier of disease and the ER stress response. PLoS genetics 20 30081392
2016 Late cornified envelope (LCE) proteins: distinct expression patterns of LCE2 and LCE3 members suggest nonredundant roles in human epidermis and other epithelia. The British journal of dermatology 20 26556599
2020 Quantitative Phosphoproteomic Analysis Reveals the Regulatory Networks of Elovl6 on Lipid and Glucose Metabolism in Zebrafish. International journal of molecular sciences 19 32325903
2018 Molecular characterization of elongase of very long-chain fatty acids 6 (elovl6) genes in Misgurnus anguillicaudatus and their potential roles in adaptation to cold temperature. Gene 19 29733968
2020 Two Elongases, Elovl4 and Elovl6, Fulfill the Elongation Routes of the LC-PUFA Biosynthesis Pathway in the Orange Mud Crab (Scylla olivacea). Journal of agricultural and food chemistry 17 32186869
2010 Discovery and characterization of a novel potent, selective and orally active inhibitor for mammalian ELOVL6. European journal of pharmacology 17 20045404
2022 ELOVL6 deficiency aggravates allergic airway inflammation through the ceramide-S1P pathway in mice. The Journal of allergy and clinical immunology 16 36592705
2021 ELOVL6 promoter binding sites directly targeted by sterol regulatory element binding protein 1 in fatty acid synthesis of goat mammary epithelial cells. Journal of dairy science 16 33685712
2014 Ablation of Elovl6 protects pancreatic islets from high-fat diet-induced impairment of insulin secretion. Biochemical and biophysical research communications 15 24938128
2021 Elongase of very long chain fatty acids 6 (ELOVL6) promotes lipid synthesis in buffalo mammary epithelial cells. Journal of animal physiology and animal nutrition 12 33742447
2020 Molecular Characterization, Nutritional and Insulin Regulation of Elovl6 in Rainbow Trout (Oncorhynchus mykiss). Biomolecules 11 32050615
2013 Genetic analysis of the ELOVL6 gene polymorphism associated with type 2 diabetes mellitus. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 10 23903678
2011 TALE homeodomain proteins regulate site-specific terminal differentiation, LCE genes and epidermal barrier. Journal of cell science 10 21511732
2024 Identifying MSMO1, ELOVL6, AACS, and CERS2 related to lipid metabolism as biomarkers of Parkinson's disease. Scientific reports 9 39080336
2022 Glioblastoma Multiforme Tumors in Women Have a Lower Expression of Fatty Acid Elongases ELOVL2, ELOVL5, ELOVL6, and ELOVL7 than in Men. Brain sciences 9 36291290
2016 Crucial Role of Elovl6 in Chondrocyte Growth and Differentiation during Growth Plate Development in Mice. PloS one 9 27467521
2013 A novel t(4;16)(q25;q23.1) associated with EGF and ELOVL6 deregulation in acute myeloid leukemia. Gene 9 23933272
2025 Targeting ELOVL6 to disrupt c-MYC driven lipid metabolism in pancreatic cancer enhances chemosensitivity. Nature communications 8 39956817
2023 Identification of key microRNAs regulating ELOVL6 and glioblastoma tumorigenesis. BBA advances 8 37082255
2024 ELOVL6 promotes the progression of head and neck squamous cell carcinoma via activating WNT/β-catenin pathway. Molecular carcinogenesis 7 38426809
2023 Cloning and expression characterization of elongation of very long-chain fatty acids protein 6 (elovl6) with dietary fatty acids, ambient salinity and starvation stress in Scylla paramamosain. Frontiers in physiology 7 37520818
2020 Dietary supplementation with myo-inositol reduces high-fructose diet-induced hepatic ChREBP binding and acetylation of histones H3 and H4 on the Elovl6 gene in rats. Nutrition research (New York, N.Y.) 7 33743322
2019 FADS2 and ELOVL6 mutation frequencies in Japanese Crohn's disease patients. Drug discoveries & therapeutics 7 31956234
2024 Emerging insights on the role of Elovl6 in human diseases: Therapeutic challenges and opportunities. Life sciences 6 39675554
2018 Association between LCE gene polymorphisms and psoriasis vulgaris among Mongolians from Inner Mongolia. Archives of dermatological research 6 29397434
2017 MiR-144 affects fatty acid composition by regulating ELOVL6 expression in duck hepatocytes. Cell biology international 6 28225172
2015 [SREBP-1c and Elovl6 as Targets for Obesity-related Disorders]. Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 6 26329544
2024 m6A Methylation Mediates the Function of the circRNA-08436/miR-195/ELOVL6 Axis in Regards to Lipid Metabolism in Dairy Goat Mammary Glands. Animals : an open access journal from MDPI 5 38929334
2022 [Role of Fatty Acid Elongase Elovl6 in the Regulation of Fatty Acid Quality and Lifestyle-related Diseases]. Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 5 35491151
2024 Low expression of ELOVL6 may be involved in fat loss in white adipose tissue of cancer-associated cachexia. Lipids in health and disease 4 38760797
2023 The ELOVL6 homolog in Penaeus vannamei plays a dual role in fatty acid metabolism and immune response. Molecular immunology 4 37875037
2016 [Expression and clinical significance of ELOVL6 gene in high-grade serous ovarian carcinoma]. Zhonghua fu chan ke za zhi 4 27030498
2025 Inhibition of ELOVL6 activity impairs mitochondrial respiratory function and inhibits tumor progression in FGFR3-mutated bladder cancer cells. Biochimica et biophysica acta. Molecular basis of disease 3 40835210
2024 Silencing the fatty acid elongase gene elovl6 induces reprogramming of nutrient metabolism in male Oreochromis niloticus. International journal of biological macromolecules 3 38806081
2025 Total saponins from Panax japonicus alleviate insulin resistance via exosomal miR204/Elovl6-mediated adipocyte-macrophage crosstalk. Phytomedicine : international journal of phytotherapy and phytopharmacology 2 40253742
2024 Alleviation effects of dexmedetomidine on myocardial ischemia/reperfusion injury through fatty acid metabolism pathway via Elovl6. International immunopharmacology 2 38955031
2024 Regulatory mechanism of Elovl6 in lipid metabolism, antioxidant capacity, and immune function in Scylla paramamosain revealed by Ap-1. International journal of biological macromolecules 2 39551296
2009 Identification and characterization of a selective radioligand for ELOVL6. Journal of biochemistry 2 19505953
2025 Dietary Oleic Acid and SCD16 and ELOVL6 Estimated Activities Can Modify Erythrocyte Membrane n-3 and n-6 HUFA Partition: A Pilot Study. Current issues in molecular biology 1 39996802
2025 FPR2 Agonism Attenuates Restenosis by Mitigating Neointimal Hyperplasia via ELOVL6. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 40913417
2025 ELOVL6 activity attenuation induces mutant KRAS degradation. Nature chemical biology 1 40954224
2016 Plesiomonas shigelloides exports a lethal cytotoxic-enterotoxin (LCE) by membrane vesicles. The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases 1 27770615
2026 Elovl6 inhibits colorectal cancer progression through stearic acid-mediated mitochondrial fusion and metabolic reprogramming. Science advances 0 41686894
2026 Regulatory Mechanisms of Sterol Regulatory Element-Binding Protein-Dependent Human ELOVL6 Expression in Response to Free Fatty Acids. Cureus 0 41768220
2026 Dietary supplementation of myo-inositol for preventing fatty liver disease by altering hepatic epigenetic modifications in the transcribed regions of Fasn and Elovl6. Biomedical research (Tokyo, Japan) 0 41882829
2025 Cholesterol Intake and Atorvastatin Modulate SCD1 and ELOVL6 in Rat Retroperitoneal Adipose Tissue. Fundamental & clinical pharmacology 0 40958209
2025 Genetic variation and mRNA expression of the ELOVL6 and CRTC2 genes in Kalmyk cattle. Animal biotechnology 0 41289344
2025 Exploring phytochemical inhibitors of fatty acid elongase ELOVL6 for targeted treatment of chronic myeloid leukemia: A comprehensive network-based drug discovery approach. Computers in biology and medicine 0 41421092