Affinage

ELOVL6

Very long chain fatty acid elongase 6 · UniProt Q9H5J4

Length
265 aa
Mass
31.4 kDa
Annotated
2026-06-09
85 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ELOVL6 is the microsomal fatty acid elongase that catalyzes the rate-limiting conversion of palmitate (C16:0) to stearate (C18:0), and as the sole enzyme for this step it sets the cellular C16-to-C18 saturated fatty acid balance that propagates into downstream phospholipid, ceramide, and monounsaturated fatty acid pools (PMID:17906635, PMID:25281760). Its enzymatic output is allosterically amplified by physical engagement with the downstream elongation enzyme KAR, which both induces an activity-enhancing conformational change in ELOVL6 and accelerates product release from the ELOVL6–KAR complex (PMID:25003994). Transcription of ELOVL6 is driven directly by SREBP-1 through high-affinity SRE elements in its promoter (PMID:18226595, PMID:33685712) and by ChREBP, whose binding is coupled to histone H3/H4 acetylation at the locus under high-carbohydrate conditions (PMID:33743322); c-MYC also transactivates ELOVL6 in pancreatic cancer (PMID:39956817), and the message is held in check post-transcriptionally by multiple miRNAs (miR-135a/b-5p, miR-125a/b-5p, miR-22-3p) acting on its 3'-UTR (PMID:37082255). By tuning lipid composition, ELOVL6 functions as a checkpoint across metabolic, inflammatory, and oncogenic processes: it governs hepatic insulin signaling through PKCε/IRS-2/Akt (PMID:17906635), palmitate-driven NLRP3 inflammasome activation in NASH (PMID:22753171), saturated- and oleate-mediated lipotoxic ER stress and apoptosis in pancreatic β-cells (PMID:21266672, PMID:28461456), foam-cell formation and cholesterol efflux in macrophages and demyelinating lesions via the S1P/PPARγ–ABCA1 axis (PMID:21817094, PMID:37669365), ceramide–S1P-dependent airway inflammation (PMID:36592705), and mitochondrial integrity through phosphatidylethanolamine supply and stearate-dependent MFN1 stabilization (PMID:40835210, PMID:41686894). In cancer, ELOVL6 supplies the phospholipid species required for KRAS-G12V membrane anchorage (PMID:40954224) and for membrane biophysical properties affecting drug uptake (PMID:39956817), making it a tractable small-molecule target (PMID:19505953, PMID:40954224).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2007 High

    Established ELOVL6 as the elongase converting palmitate to stearate in vivo and linked its lipid output to hepatic insulin signaling, framing it as a metabolic checkpoint rather than a housekeeping enzyme.

    Evidence Elovl6 knockout mice on high-fat diet and ob/ob crosses, with hepatic IRS-2, PKCε, and Akt readouts

    PMID:17906635

    Open questions at the time
    • Insulin-resistance protection was later not reproduced in an independent KO line
    • Direct molecular link between fatty acid composition and PKCε activity not resolved
  2. 2008 High

    Identified the transcriptional control point for ELOVL6, showing SREBP-1c binds defined SRE elements to drive its expression, placing the gene within lipogenic transcriptional programs.

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

    PMID:18226595

    Open questions at the time
    • Did not address combinatorial regulation with other lipogenic transcription factors
  3. 2009 Medium

    Demonstrated ELOVL6 is selectively druggable and that inhibitor binding depends on palmitoyl-CoA, implying recognition of an acyl-enzyme intermediate and giving a chemical handle on catalysis.

    Evidence In vitro inhibition and [³H]Compound-A radioligand binding with selectivity profiling across ELOVL family

    PMID:19505953

    Open questions at the time
    • No structural model of the inhibitor-bound enzyme
    • Single lab, single chemical series
  4. 2010 Medium

    Tested whether pharmacological ELOVL6 inhibition recapitulates the genetic insulin-sensitizing phenotype; chronic dosing altered hepatic fatty acid composition but did not improve insulin resistance.

    Evidence Oral ELOVL6 inhibitor in DIO and KKAy mice with hepatic lipid and insulin-resistance measurement

    PMID:20045404

    Open questions at the time
    • Discordance with genetic KO insulin phenotype unexplained
    • Inhibitor exposure/target engagement in non-hepatic tissues not quantified
  5. 2011 Medium

    Extended ELOVL6 beyond metabolism into vascular and β-cell pathology, showing its lipid output determines macrophage foam-cell formation/cholesterol efflux and saturated-fat lipotoxicity.

    Evidence Bone marrow transplant of Elovl6−/− cells into LDL-R−/− mice with efflux assays; gain/loss-of-function in INS-1 β-cells

    PMID:21266672 PMID:21817094

    Open questions at the time
    • Molecular link between elongated fatty acids and efflux transporter induction not fully defined
    • β-cell findings limited to a single cell line
  6. 2012 High

    Connected ELOVL6 lipid output to innate immune activation, showing palmitate-driven NLRP3 inflammasome activity underlies its role in steatohepatitis progression.

    Evidence Three Elovl6 loss- and gain-of-function mouse models on atherogenic diet with NLRP3 inflammasome readouts and human NASH samples

    PMID:22753171

    Open questions at the time
    • Mechanism by which palmitate engages NLRP3 not delineated at molecular level
  7. 2013 High

    An independent KO line refined ELOVL6 substrate specificity (sole C16:0→C18:0 elongase, palmitoleate elongation not specific) but failed to reproduce protection from metabolic disease, exposing model-dependence of the insulin phenotype.

    Evidence Independent Elovl6 KO with high-fat and ob/ob crosses and mass-spectrometry lipidomics

    PMID:25281760

    Open questions at the time
    • Source of discordance with the 2007 insulin phenotype unresolved
    • Genetic background contributions not isolated
  8. 2013 High

    Showed ELOVL6-dependent fatty acid balance maintains epithelial homeostasis, with its loss driving apoptosis, ROS, TGF-β1, and fibrosis in lung after injury.

    Evidence Elovl6 KO mouse with bleomycin challenge plus siRNA knockdown, ROS/apoptosis/TGF-β1 assays

    PMID:24113622

    Open questions at the time
    • Specific lipid species driving the fibroproliferative response not pinpointed
  9. 2014 High

    Defined the biochemical basis for ELOVL6 activity regulation, revealing KAR enhances ELOVL6 both by conformational change and by enzymatic product release within a presumed complex.

    Evidence In vitro elongation assays with purified ELOVL6 and wild-type vs catalytically dead KAR mutants, with NADPH dependence

    PMID:25003994

    Open questions at the time
    • Structure of the ELOVL6–KAR complex not determined
    • Stoichiometry and in vivo relevance of the interaction untested
  10. 2014 Medium

    Linked ELOVL6 to islet secretory function, with its ablation improving glucose-stimulated insulin secretion via ATP/ADP ratio and ATF-3 suppression.

    Evidence Elovl6 KO mice on high-fat/high-sucrose diet with islet GSIS, ATP/ADP, and ATF-3 measurement

    PMID:24938128

    Open questions at the time
    • Causal lipid mediator linking elongation to ATP/ADP ratio not identified
    • Single lab
  11. 2015 Medium

    Showed ELOVL6-mediated C16→C18 conversion is required for full brown-fat thermogenic capacity through support of mitochondrial electron transport chain expression.

    Evidence Elovl6 KO mice with cold exposure, ETC component expression, and thermogenesis measurements

    PMID:26628376

    Open questions at the time
    • Mechanism connecting fatty acid chain length to ETC component levels unresolved
    • Single lab
  12. 2016 Medium

    Established ELOVL6 as a regulator of vascular smooth muscle phenotype and chondrocyte/skeletal development, broadening its lipid-composition checkpoint role to differentiation programs.

    Evidence Elovl6−/− mice in wire-injury neointima model with VSMC ROS/AMPK/KLF4 epistasis; skeletal histology and Foxa2/HDAC analysis in chondrocytes

    PMID:27467521 PMID:27881420

    Open questions at the time
    • How altered oleate/palmitate ratios initiate ROS/AMPK signaling not mechanistically closed
    • Chondrocyte findings from a single lab
  13. 2017 High

    Resolved the lipotoxic culprit downstream of ELOVL6 in diabetic islets, identifying elevated oleate as the driver of ER stress, inflammation, and β-cell apoptosis whose removal expands β-cell mass.

    Evidence Elovl6 deletion in db/db mice with β-cell morphometry and ex vivo islet palmitate/oleate challenge

    PMID:28461456

    Open questions at the time
    • Receptor/sensor for oleate-induced ER stress not identified
  14. 2018 Medium

    Placed ELOVL6-dependent C18 fatty acid production upstream of UPR signaling and skin barrier inflammation, with stearate supplementation bypassing the requirement for the enzyme.

    Evidence Drosophila Baldspot loss-of-function with Rh1G69D ER-stress model and dietary stearate rescue; Elovl6 KO keratinocyte tape-stripping model with DAMP/cytokine readouts

    PMID:30081392 PMID:30518914

    Open questions at the time
    • How stearate availability modulates IRE1/PERK signaling biochemically not defined
    • Findings from single labs in distinct systems
  15. 2020 Medium

    Added an epigenetic and second-transcription-factor layer, showing ChREBP binds the Elovl6 promoter and drives histone acetylation in fructose-induced fatty liver.

    Evidence ChIP for ChREBP/SREBP-1 binding and histone acetylation with myo-inositol intervention in a rat dietary model

    PMID:33743322

    Open questions at the time
    • Relative contributions of ChREBP versus SREBP-1 not quantified
    • Rat model only
  16. 2021 Medium

    Linked ELOVL6 to therapy response in cancer, showing ELOVL6-dependent ceramide species are required for bortezomib-induced ER stress and that interaction with ACSL4 places it in the ferroptosis pathway.

    Evidence Knockdown/restoration in multiple myeloma cells with lipidomics and xenograft; co-IP and overexpression in colorectal HCT116 ferroptosis assays

    PMID:33603479 PMID:33821992

    Open questions at the time
    • ACSL4 interaction rests on a single co-IP without reciprocal validation
    • Mechanism linking ELOVL6 elongation to ceramide synthesis not directly mapped
  17. 2022 High

    Defined ELOVL6 as an upstream brake on the ceramide–S1P axis in airway immunity, with its loss elevating ceramide/S1P and aggravating allergic inflammation reversible by pathway inhibitors.

    Evidence Elovl6 KO mice in OVA and HDM asthma models with lipidomics and ceramide synthase/sphingosine kinase inhibitor rescue

    PMID:36592705

    Open questions at the time
    • How loss of C18 fatty acids shifts flux toward ceramide/S1P not biochemically detailed
  18. 2023 High

    Showed ELOVL6 drives a pro-inflammatory phagocyte phenotype during demyelination via the S1P/PPARγ–ABCA1 axis, and identified human miRNAs that post-transcriptionally repress it.

    Evidence Myelin-induced foam cell model, Elovl6 depletion with S1P/PPARγ and ABCA1 readouts, organotypic slices and cuprizone model; dual-luciferase 3'-UTR assays in glioblastoma cells

    PMID:37082255 PMID:37669365

    Open questions at the time
    • Whether the same miRNAs regulate ELOVL6 in phagocytes not tested
    • Lipid species coupling ELOVL6 to S1P/PPARγ activation not specified
  19. 2025 High

    Revealed an oncogene-supporting role in which ELOVL6 supplies phospholipids required for KRAS-G12V membrane anchorage and membrane biophysics, and showed c-MYC drives its expression, validating it as a small-molecule target in cancer.

    Evidence Genome-wide CRISPR-Cas9 screen, lipidomics, and ELOVL6 inhibitor clearing KRAS-G12V; PDAC models with c-MYC ChIP/reporter, membrane biophysics, pinocytosis, and Abraxane response

    PMID:39956817 PMID:40954224

    Open questions at the time
    • Identity of the specific KRAS-anchoring phospholipid species incompletely defined
    • Therapeutic window of ELOVL6 inhibition in vivo not established
  20. 2025 Medium

    Connected ELOVL6 to mitochondrial structure and function in cancer, showing knockdown depletes phosphatidylethanolamine and impairs OXPHOS with compensatory ECM-integrin-FAK signaling.

    Evidence ELOVL6 knockdown in FGFR3-mutant bladder cancer cells with lipidomics, RNA-seq, OXPHOS assays, and in vivo tumor growth

    PMID:40835210

    Open questions at the time
    • Whether PE loss directly causes the complex I/II decline not isolated
    • Single lab
  21. 2026 Medium

    Provided a molecular mechanism for ELOVL6's effect on mitochondrial dynamics, showing its product stearate stabilizes MFN1 to promote mitochondrial fusion.

    Evidence Elovl6 KO cells and mouse models with phospholipid profiling, MFN1 stability and mitochondrial morphology assays, and in vivo tumor growth

    PMID:41686894

    Open questions at the time
    • Biochemical mechanism by which stearate stabilizes MFN1 protein not defined
    • Single lab, recent finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unifying biochemical and structural account of how ELOVL6-set C16/C18 ratios are transduced into the diverse downstream signaling outcomes (PKCε, NLRP3, ceramide-S1P, KRAS anchorage, MFN1) remains unresolved.
  • No atomic-resolution structure of ELOVL6 or the ELOVL6–KAR complex
  • The specific lipid intermediates linking elongation to each downstream pathway are not consistently identified
  • Reconciliation of discordant metabolic phenotypes across independent KO lines is incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 3
Localization
GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-168256 Immune System 3 R-HSA-1430728 Metabolism 2
Partners
ACSL4KAR
Complex memberships
ELOVL6-KAR elongase complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 ELOVL6 is the microsomal elongase that catalyzes the conversion of palmitate (C16:0) to stearate (C18:0). Elovl6-knockout mice become obese and develop hepatosteatosis on high-fat diet but are markedly protected from hyperinsulinemia and hyperglycemia. The mechanism involves restoration of hepatic insulin receptor substrate-2 (IRS-2) and suppression of hepatic protein kinase C epsilon (PKCε) activity, resulting in restoration of Akt phosphorylation. Elovl6 knockout mouse model; high-fat diet and ob/ob mouse crosses; 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 SREBP binding sites (proximal SRE-1 and distal SRE-2) were identified, with SRE-1 showing higher affinity. SREBP-1c binds the Elovl6 promoter in vivo, and adenoviral RNAi knockdown of SREBP-1 in mouse liver suppresses Elovl6 mRNA. Luciferase reporter assays, EMSA, chromatin immunoprecipitation (ChIP), adenoviral RNAi knockdown in mouse liver Biochemical and biophysical research communications High 18226595
2009 A selective inhibitor (Compound A, an indoledione) was identified that potently inhibits human and mouse ELOVL6 with >100-fold selectivity over other ELOVL family members. A tritiated form ([³H]Compound-A) binds ELOVL6 in a palmitoyl-CoA-dependent manner in the absence of malonyl-CoA and NADPH, suggesting it recognizes an acyl-enzyme intermediate. Biochemical inhibition assay; radioligand binding assay with [³H]Compound-A; selectivity profiling across ELOVL family members Journal of biochemistry Medium 19505953
2010 A novel orally active ELOVL6 inhibitor (Compound B) was developed that effectively inhibits ELOVL6 activity in vivo in diet-induced obese and KKAy mice, significantly reducing hepatic fatty acid composition. However, no improvement in insulin resistance was observed in these chronic pharmacological studies. In vivo chronic dosing of selective ELOVL6 inhibitor in DIO and KKAy mice; hepatic fatty acid composition analysis; insulin resistance measurement European journal of pharmacology Medium 20045404
2011 ELOVL6 in macrophages promotes foam cell formation and atherosclerosis. Elovl6-deficient macrophages accumulate less esterified cholesterol upon acetylated-LDL exposure, show increased cholesterol efflux and upregulated cholesterol efflux transporters, and bone marrow transplantation of Elovl6−/− cells into LDL-R−/− mice results in significantly smaller aortic atherosclerotic lesions. Bone marrow transplantation into irradiated LDL-R−/− mice; cholesterol efflux assay; fatty acid composition analysis of esterified cholesterol fraction in macrophages Arteriosclerosis, thrombosis, and vascular biology High 21817094
2011 ELOVL6 overexpression in pancreatic β-cells (INS-1) increases palmitate elongation to stearate and increases palmitate-induced ER stress and apoptosis, whereas ELOVL6 knockdown limits palmitate elongation and attenuates ER stress and apoptosis. This establishes ELOVL6 activity as a determinant of saturated fatty acid lipotoxicity in β-cells. Overexpression and RNAi knockdown in INS-1 cells; fatty acid profiling; ER stress and apoptosis assays American journal of physiology. Endocrinology and metabolism Medium 21266672
2012 ELOVL6 is a critical modulator of nonalcoholic steatohepatitis (NASH). Using three independent mouse models (loss and gain of function), deletion of Elovl6 reduces atherogenic diet-induced hepatic inflammation, oxidative stress, and fibrosis. Mechanistically, deletion of Elovl6 reduces palmitate-induced activation of the NLRP3 inflammasome. Elovl6 knockout and adenoviral overexpression mouse models; NASH dietary challenge; NLRP3 inflammasome activation assays; human NASH liver samples for expression correlation Hepatology (Baltimore, Md.) High 22753171
2013 ELOVL6 is the only enzyme capable of elongating palmitate (C16:0) to stearate (C18:0); Elovl6−/− mice accumulate palmitic and palmitoleic acids and are severely depleted of stearic and oleic acids. Unexpectedly, palmitoleate (C16:1 n-7) elongation to vaccenate (C18:1 n-7) was not specific to ELOVL6. Deletion of ELOVL6 did not protect mice from obesity, fatty liver, hyperglycemia, or hyperinsulinemia on a high-fat diet or in ob/ob background (contradicting PMID 17906635 in some respects). Elovl6 knockout mouse generation; high-fat diet and ob/ob crosses; detailed hepatic fatty acid profiling by mass spectrometry Journal of lipid research High 25281760
2013 Loss of Elovl6 in alveolar type II epithelial cells causes derangement of fatty acid profile, induces apoptosis, TGF-β1 expression, and reactive oxygen species generation; Elovl6-deficient mice exhibit severe fibroproliferative response to bleomycin, establishing a role for ELOVL6 in maintaining lung homeostasis. Elovl6 knockout mouse + bleomycin intratracheal instillation model; Elovl6 siRNA knockdown in cells; fatty acid profiling; apoptosis and ROS assays; TGF-β1 measurement Nature communications High 24113622
2014 KAR (3-ketoacyl-CoA reductase), which catalyzes the second step of the FA elongation cycle, regulates ELOVL6 via two modes: (1) a KAR enzyme activity-independent mode in which KAR protein induces conformational changes in ELOVL6 (~3-fold activity enhancement), and (2) a KAR enzyme activity-dependent mode in which conversion of 3-ketoacyl-CoA to 3-hydroxyacyl-CoA facilitates product release from a presumed ELOVL6-KAR complex, further enhancing ELOVL6 activity (~10-fold with NADPH present). In vitro FA elongation assays using membrane fractions; purified ELOVL6 activity assay with wild-type and catalytically dead KAR mutants; NADPH dependence experiments PloS one High 25003994
2014 Elovl6 ablation protects pancreatic islets from high-fat/high-sucrose diet-induced impairment: Elovl6−/− islets show increased glucose-stimulated insulin secretion (GSIS) associated with an increased ATP/ADP ratio and suppression of ATF-3 expression, indicating Elovl6 affects insulin secretory capacity per β-cell. Elovl6 knockout mouse; HFHS diet challenge; islet GSIS measurement; ATP/ADP ratio; ATF-3 expression Biochemical and biophysical research communications Medium 24938128
2015 Elovl6 is necessary for brown adipose tissue (BAT) thermogenic capacity. Loss of Elovl6 does not alter canonical BAT markers but reduces expression of mitochondrial electron transport chain components and lowers BAT thermogenic capacity, converting C16 to C18 fatty acid species being required for full thermogenic function. Elovl6 knockout mice; cold exposure; mitochondrial ETC component expression; BAT thermogenesis measurement; thermoneutrality and aging experiments Cell reports Medium 26628376
2016 Elovl6 inhibition in vascular smooth muscle cells (VSMCs) induces phenotypic switching via ROS production and AMPK/KLF4 signaling. Reduced oleate and increased palmitate from Elovl6 deficiency lead to ROS production, AMPK activation, induction of p53/p21, reduced mTOR phosphorylation, and robust KLF4 induction. KLF4 knockdown attenuates AMPK-induced phenotypic switching, identifying KLF4 as a bona fide AMPK target. Elovl6-null mice show markedly inhibited neointima formation after wire injury. Elovl6−/− mice with wire injury model; siRNA knockdown in VSMCs; PDGF-BB stimulation; ROS measurement; AMPK, mTOR phosphorylation; KLF4 KD epistasis Journal of the American Heart Association High 27881420
2016 Elovl6 plays a crucial role in chondrocyte growth and differentiation during growth plate development. Elovl6-null mice have reduced proliferating chondrocyte layer, elongated hypertrophic zone, and decreased trabecular bone. Elovl6 ablation elevates Collagen10α1 expression, associated with increased Foxa2/a3 and Mef2c mRNA and elevated nuclear Foxa2 and cytoplasmic HDAC4/5/7 protein levels. Elovl6 knockout mice; skeletal histology; gene expression analysis; protein level measurement of Foxa2, HDAC4/5/7 in chondrocytes PloS one Medium 27467521
2017 In db/db mice (T2D model), Elovl6 deletion markedly increases β-cell mass with increased proliferation and decreased apoptosis. Elevated oleate (C18:1n-9) characterizes db/db islets and causes ER stress, inflammation, and apoptosis; Elovl6 deletion completely suppresses these. Ex vivo, Elovl6−/− islets exhibit reduced susceptibility to palmitate-induced inflammation, ER stress, and β-cell apoptosis, implicating oleate as the lipotoxic culprit downstream of ELOVL6. Elovl6 deletion in db/db mice; β-cell mass morphometry; islet isolation and ex vivo palmitate/oleate treatment; ER stress, inflammation, and apoptosis assays Diabetes High 28461456
2018 Loss of Elovl6 in Drosophila (Baldspot, the ELOVL6 ortholog) rescues retinal degeneration in a rhodopsin-G69D ER stress model by reducing IRE1 and PERK signaling and cell death. Dietary supplementation with stearate bypasses the need for Baldspot/ELOVL6 activity, placing ELOVL6-dependent C18 fatty acid production upstream of ER stress signaling. Drosophila genetic loss-of-function; retinitis pigmentosa ER stress model (Rh1G69D); IRE1 and PERK signaling measurement; dietary stearate supplementation rescue PLoS genetics Medium 30081392
2018 Elovl6 in keratinocytes regulates the balance of cis-vaccenic acid (CVA) levels in the epidermis. Elovl6-deficient mice accumulate higher CVA levels in epidermis; CVA accelerates tape stripping-triggered keratinocyte death and DAMP release (HMGB-1, IL-1α), inducing proinflammatory cytokines IL-1β and CXCL-1, causing severe mechanical damage-induced skin inflammation. Elovl6 knockout mice; tape stripping model; CVA fatty acid profiling; keratinocyte death and DAMP release assays; cytokine measurement Cell death & disease Medium 30518914
2021 ELOVL6 levels are lower in bortezomib-resistant multiple myeloma (MM) cells. Restoration of ELOVL6 in BTZ-resistant MM cells resensitizes them to bortezomib through upregulation of ELOVL6-dependent ceramide species, which are prerequisite for BTZ-induced ER stress and cell death. Depletion of ELOVL6 in parental MM cells suppresses BTZ-induced ER stress and cytotoxicity. ELOVL6 knockdown and restoration in MM cell lines; lipidomics of BTZ-induced lipidome changes; xenograft plasmacytoma mouse model; cell death and ER stress assays Blood advances High 33821992
2021 ELOVL6 directly interacts with ACSL4 (a key regulator of ferroptosis) as confirmed by co-immunoprecipitation. ELOVL6 overexpression reverses apatinib-induced ferroptosis in colorectal cancer HCT116 cells, placing ELOVL6 upstream of ACSL4 in the ferroptosis pathway. Co-immunoprecipitation (co-IP); ELOVL6 overexpression in HCT116 cells; CCK-8 cell viability; iron/ROS measurement; Western blot of ferroptosis markers Cancer management and research Low 33603479
2021 SREBP1 directly binds to SRE1 and SRE3 sites in the ELOVL6 promoter in goat mammary epithelial cells. Mutation of either SRE1 or SRE3 significantly reduced promoter activity; simultaneous mutation abolished SREBF1-stimulatory and linoleic acid-repressive effects on ELOVL6 transcription. Promoter deletion analysis; site-directed mutagenesis; luciferase reporter assay; ChIP assay in goat mammary epithelial cells (GMEC) Journal of dairy science Medium 33685712
2022 ELOVL6 deficiency aggravates allergic airway inflammation via the ceramide-S1P pathway. Elovl6−/− asthmatic mice have elevated palmitic acid, ceramide, and sphingosine-1-phosphate in lung tissue, and enhanced lymphocyte egress from lymph nodes with upregulated type 2 and non-type 2 immune responses. Treatment with fumonisin B1 (ceramide synthase inhibitor) or DL-threo-dihydrosphingosine (sphingosine kinase inhibitor) ameliorates the aggravated inflammation, placing ELOVL6 upstream of ceramide-S1P biosynthesis in airway inflammation. Elovl6 knockout mice; OVA and HDM asthma models; lipidomic profiling; pharmacological inhibition of ceramide synthase and sphingosine kinase The Journal of allergy and clinical immunology High 36592705
2023 ELOVL6 promotes inflammatory foam cell formation during demyelination, hampering remyelination. ELOVL6 is upregulated in myelin-phagocytosing phagocytes and MS lesions. Elovl6 depletion induces a repair-promoting phagocyte phenotype via S1P/PPARγ pathway activation, enhancing ABCA1-mediated lipid efflux and increasing neurotrophic factor production while reducing inflammatory mediators. In vivo, Elovl6 deficiency prevented demyelination and boosted remyelination in organotypic brain slice cultures and the cuprizone model. In vitro myelin-induced foam cell model; Elovl6 depletion; S1P/PPARγ signaling assays; ABCA1 efflux measurement; 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 downregulate ELOVL6 by binding its 3'-UTR. miR-135b-5p and miR-135a-5p suppress glioblastoma cell proliferation and migration specifically by inhibiting ELOVL6 at the mRNA and protein levels. Dual-luciferase reporter assays with ELOVL6 3'-UTR constructs; miRNA overexpression in GBM cells; cell proliferation and migration assays BBA advances Medium 37082255
2025 ELOVL6 activity is required for production of phospholipids that KRAS-G12V exploits for membrane association. CRISPR-Cas9 genome-wide KO screens identified ELOVL6 as a selective modulator of KRAS-G12V protein expression. ELOVL6 targeting depletes specific phospholipid species, leading to function-targeted and trigger-targeted degradation of KRAS-G12V protein. A first-in-class small-molecule ELOVL6 inhibitor selectively clears KRAS-G12V from cancer cells. CRISPR-Cas9 genome-wide knockout screen; lipidomics; ELOVL6 inhibitor treatment; KRAS protein expression and degradation assays in cell lines Nature chemical biology High 40954224
2025 c-MYC directly upregulates ELOVL6 transcription during PDAC tumor progression. Genetic or chemical inhibition of ELOVL6 reduces cancer cell proliferation and migration by altering fatty acid composition, changing membrane rigidity, permeability, and pinocytosis, increasing Abraxane uptake and showing synergistic anti-tumor effects in vivo. PDAC mouse models; c-MYC ChIP/reporter for ELOVL6 regulation; ELOVL6 KD and inhibitor; fatty acid profiling; membrane biophysics; pinocytosis assays; in vivo tumor growth and Abraxane response Nature communications High 39956817
2025 ELOVL6 knockdown in FGFR3-mutant bladder cancer cells causes marked reduction in phosphatidylethanolamine, lowers mitochondrial complex I and II protein levels, and impairs mitochondrial oxidative phosphorylation (OXPHOS). This is accompanied by activation of ECM-integrin-FAK pathway as a compensatory response. ELOVL6 knockdown suppresses tumor progression in vivo. ELOVL6 knockdown in BC cell lines; lipidomics; RNA sequencing; mitochondrial OXPHOS assay; in vivo tumor growth assay Biochimica et biophysica acta. Molecular basis of disease Medium 40835210
2026 Stearic acid (the direct product of ELOVL6 activity) promotes mitochondrial fusion by stabilizing mitofusin 1 (MFN1) protein in colorectal cancer cells. Elovl6 deficiency disrupts phospholipid biosynthesis, reduces stearic acid, destabilizes MFN1, impairs mitochondrial fusion, and promotes CRC progression. Elovl6 KO cells and mouse models; phospholipid profiling; MFN1 protein stability assay; mitochondrial morphology analysis; in vivo tumor growth Science advances Medium 41686894
2020 ChREBP binds to the Elovl6 promoter in vivo and drives histone H3 and H4 acetylation at the Elovl6 locus in high-fructose diet-induced fatty liver. myo-Inositol supplementation reduces ChREBP binding and histone acetylation at the Elovl6 promoter, suppressing Elovl6 expression. ChIP assay for ChREBP and SREBP-1 binding to Elovl6 promoter; histone acetylation ChIP; rat dietary model; qPCR Nutrition research (New York, N.Y.) Medium 33743322

Source papers

Stage 0 corpus · 85 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 433 17906635
2009 Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nature genetics 363 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
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 95 21266672
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
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 89 21435436
2021 Apatinib Promotes Ferroptosis in Colorectal Cancer Cells by Targeting ELOVL6/ACSL4 Signaling. Cancer management and research 69 33603479
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
2015 Brown Adipose Tissue Thermogenic Capacity Is Regulated by Elovl6. Cell reports 67 26628376
2017 Psoriasis-Associated Late Cornified Envelope (LCE) Proteins Have Antibacterial Activity. The Journal of investigative dermatology 64 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 54 23341976
2018 Elovl6 is a negative clinical predictor for liver cancer and knockdown of Elovl6 reduces murine liver cancer progression. Scientific reports 50 29700319
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
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
2019 Effect of ELOVL6 on the lipid metabolism of bovine adipocytes. Genomics 36 31901374
2017 Elovl6 Deficiency Improves Glycemic Control in Diabetic db/db Mice by Expanding β-Cell Mass and Increasing Insulin Secretory Capacity. Diabetes 36 28461456
2020 Role of fatty acid elongase Elovl6 in the regulation of energy metabolism and pathophysiological significance in diabetes. Diabetology international 33 33479581
2015 Epigenetic regulation of the ELOVL6 gene is associated with a major QTL effect on fatty acid composition in pigs. Genetics, selection, evolution : GSE 33 25887840
2010 Variants in MHC, LCE and IL12B have epistatic effects on psoriasis risk in Chinese population. Journal of dermatological science 33 21208785
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 27 21701577
2021 The fatty acid elongase ELOVL6 regulates bortezomib resistance in multiple myeloma. Blood advances 25 33821992
2019 Molecular Cloning, Characterization, and Nutritional Regulation of Elovl6 in Large Yellow Croaker (Larimichthys crocea). International journal of molecular sciences 25 30979053
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
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 22 32120850
2017 Hepatic ELOVL6 mRNA is regulated by the gga-miR-22-3p in egg-laying hen. Gene 22 28445717
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
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 21 26556599
2020 Quantitative Phosphoproteomic Analysis Reveals the Regulatory Networks of Elovl6 on Lipid and Glucose Metabolism in Zebrafish. International journal of molecular sciences 20 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 20 29733968
2018 Baldspot/ELOVL6 is a conserved modifier of disease and the ER stress response. PLoS genetics 20 30081392
2022 ELOVL6 deficiency aggravates allergic airway inflammation through the ceramide-S1P pathway in mice. The Journal of allergy and clinical immunology 17 36592705
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
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
2025 Targeting ELOVL6 to disrupt c-MYC driven lipid metabolism in pancreatic cancer enhances chemosensitivity. Nature communications 12 39956817
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
2024 Identifying MSMO1, ELOVL6, AACS, and CERS2 related to lipid metabolism as biomarkers of Parkinson's disease. Scientific reports 10 39080336
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
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
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 Total saponins from Panax japonicus alleviate insulin resistance via exosomal miR204/Elovl6-mediated adipocyte-macrophage crosstalk. Phytomedicine : international journal of phytotherapy and phytopharmacology 3 40253742
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
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 3 39551296
2024 Alleviation effects of dexmedetomidine on myocardial ischemia/reperfusion injury through fatty acid metabolism pathway via Elovl6. International immunopharmacology 2 38955031
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
2026 miR-302 protects the liver from glucolipotoxicity-induced lipid accumulation through activating AMPK and suppressing Elovl6 in HepG2 cells and also in mice. Life sciences 0 42067127
2026 Computational Analysis of ELOVL6 Structure and Inhibition for Rational Drug Design. Journal of chemical information and modeling 0 42246265
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

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