| 2003 |
ELOVL3 is a microsomal enzyme required for elongation of fatty acids beyond 20 carbons; disruption of the Elovl3 gene in mice causes near-complete absence of fatty acids >20 carbons in triglycerides (especially in the skin/hair), with accumulation of eicosenoic acid (20:1), establishing ELOVL3 as the elongase responsible for C20+ neutral lipid fatty acid synthesis in sebaceous glands and hair follicle epithelial cells. |
Elovl3 gene knockout by homologous recombination in mouse; fatty acid profiling of hair lipids and triglyceride fractions; histological analysis of pilosebaceous system; trans-epidermal water loss measurement |
The Journal of biological chemistry |
High |
14581464
|
| 2005 |
ELOVL3 is required for elongation of saturated fatty acyl-CoAs into very long chain fatty acids (C20:0, C22:0) in brown adipose tissue; Elovl3-ablated mice show decreased condensation activity of the elongation enzyme and reduced arachidic and behenic acid levels during cold stress, establishing ELOVL3 as a critical elongase for saturated VLCFA synthesis and triglyceride formation in BAT during early tissue recruitment. |
Elovl3 knockout mice; cold acclimation protocol; in vitro elongation condensation activity assay on BAT extracts; fatty acid composition analysis; body temperature monitoring; muscle shivering measurement |
The Journal of biological chemistry |
High |
16326704
|
| 2005 |
Elovl3 expression in brown adipocytes is transcriptionally controlled by PPARα (induced by PPARα ligand Wy-14643 in concert with norepinephrine and dexamethasone), while LXR/SREBP-1 activation represses Elovl3 expression and increases Elovl1; this differential regulation establishes ELOVL3 in a distinct transcriptional program linked to oxidative (non-lipogenic) metabolic states, functionally reflected in C22:0 esterified fatty acid levels. |
Primary brown adipocyte cultures; PPARα/LXRα ligand treatments; mRNA expression analysis; nuclear LXR and SREBP-1 abundance measurement; fatty acid composition analysis of esterified lipids |
American journal of physiology. Endocrinology and metabolism |
Medium |
15855229
|
| 2006 |
Circadian expression of Elovl3 in mouse liver is perturbed in CLOCK-mutant mice and is activated by SREBP1 and repressed by RevErbα at the Elovl3 promoter; proteolytic activation of SREBP1 is itself circadian in the liver and responds to meal timing, placing ELOVL3 downstream of a clock–nutrition integration mechanism. |
CLOCK mutant mouse liver analysis; promoter reporter assays with SREBP1 and RevErbα; meal-restriction experiments with inverted feeding; hepatic dysfunction mouse model |
Journal of lipid research |
Medium |
17003504
|
| 2007 |
Elovl3 expression in brown adipocytes is synergistically induced by norepinephrine and the PPARγ ligand rosiglitazone; this induction requires novel protein synthesis, is achieved through both increased transcription and increased mRNA stability, and rosiglitazone is orders of magnitude more potent than PPARα or PPARδ ligands, placing ELOVL3 downstream of PPARγ and sympathetic activation in brown adipocyte lipid accumulation. |
Primary brown adipocyte cultures; norepinephrine and rosiglitazone (PPARγ agonist) treatment; quantitative mRNA analysis; mRNA stability assay; protein synthesis inhibitor (cycloheximide) treatment; comparison with PPARα and PPARδ ligands |
American journal of physiology. Endocrinology and metabolism |
Medium |
17726147
|
| 2008 |
Hepatic Elovl3 expression follows a sexually dimorphic circadian rhythm controlled by glucocorticoids and androgens; dexamethasone (synthetic glucocorticoid) transcriptionally induces Elovl3 in mouse liver, and expression is elevated in ABCD2-ablated mice and suppressed in ABCD2-overexpressing mice, revealing cross-talk between VLCFA synthesis (ELOVL3) and peroxisomal VLCFA oxidation (ABCD2). |
Zeitgeber time-series mRNA analysis in male/female/immature mice; fasting/refeeding and restricted feeding experiments; dexamethasone injection; ABCD2 knockout and transgenic overexpression mouse models; castration experiments |
Endocrinology |
Medium |
18292190
|
| 2010 |
ELOVL3 synthesizes C20–C24 saturated and monounsaturated VLCFAs in liver, brown and white adipose tissue, and triglyceride-rich glands; ablation reduces hepatic de novo fatty acid synthesis, fatty acid uptake, triglyceride content, and VLDL-triglyceride secretion, and constrains adipose tissue expansion, demonstrating that ELOVL3-derived VLCFAs are required for hepatic triglyceride synthesis and adipose lipid storage. |
Global Elovl3 knockout mice; diet-induced obesity model; hepatic lipogenic gene expression analysis; in vivo de novo fatty acid synthesis measurement; VLDL-TG secretion assay; serum adiponectin and leptin measurement; adipose tissue histology |
FASEB journal |
High |
20605947
|
| 2012 |
PPARγ directly binds three PPAR-responsive elements in the Elovl3 promoter to activate transcription during adipogenesis; C18:1 and C20:1 VLCFAs produced by ELOVL3 act as PPARγ agonists (coactivator recruitment in mammalian two-hybrid assay), creating a positive feedback loop (ELOVL3–VLCFA–PPARγ) that sustains adipogenic gene expression. |
3T3-L1 adipogenesis model; Elovl3 siRNA knockdown; promoter-reporter assays with PPRE mutations; chromatin immunoprecipitation (ChIP) for PPARγ at Elovl3 promoter; mammalian two-hybrid assay for C18:1 and C20:1 activation of PPARγ; PPARγ antagonist rescue experiment |
American journal of physiology. Endocrinology and metabolism |
High |
22436697
|
| 2015 |
Vitamin D receptor (VDR) directly occupies a negative-response element in the proximal Elovl3 promoter in a ligand-dependent manner, transcriptionally repressing Elovl3 expression specifically in subcutaneous white adipose tissue; VDR deletion leads to increased C18–C24 saturated and monounsaturated fatty acids in sc WAT, placing ELOVL3 as a direct VDR target responsible for tissue-specific fatty acid composition. |
VDR knockout (VDRKO) mice; fatty acid composition analysis of sc and visceral WAT depots; ChIP assay for VDR occupancy at Elovl3 promoter negative-response element; in vivo vitamin D treatment; tissue-specific gene expression analysis |
Endocrinology |
Medium |
26488808
|
| 2019 |
BRG1 (chromatin remodeling ATPase) is recruited by the nuclear receptor RORγ to the Elovl3 promoter to activate transcription in prostate cancer cells in response to androgen and TGF-β; BRG1 also interacts with histone acetyltransferase p300 at the Elovl3 promoter, and p300 inhibition or depletion attenuates Elovl3 trans-activation, linking ELOVL3 expression to BRG1–RORγ–p300 epigenetic co-activation. |
BRG1 overexpression and knockdown in prostate cancer cells; Elovl3 promoter ChIP assay for BRG1 and p300; Co-immunoprecipitation of BRG1 with RORγ; siRNA knockdown of p300; curcumin (p300 inhibitor) treatment; cell migration and invasion assays |
Biochimica et biophysica acta. Gene regulatory mechanisms |
Medium |
31154107
|
| 2019 |
ELOVL3 is required for production of C21:0–C29:0 fatty acids (including odd-chain and branched chain species) in meibomian glands; ELOVL3 ablation causes selective depletion of cholesteryl esters, wax esters, and cholesteryl esters of O-acylated ω-hydroxy fatty acids in tarsal plates, demonstrating ELOVL3's essential catalytic role in meibogenesis. |
Elovl3 knockout mice vs. wild-type; chromatographic and mass spectrometric lipid profiling of tarsal plate lipids; slit lamp examination; histological analysis of ocular tissues |
FASEB journal |
High |
31208226
|
| 2019 |
Sustained rhythmic expression of hepatic Elovl3 requires coordination between the circadian clock (BMAL1) and androgen signaling; NR1D1 (RevErbα) binds the Elovl3 promoter in a circadian-dependent manner in vivo; castration abolishes Elovl3 levels in male liver but not circadian variation, while 5α-dihydrotestosterone induces Elovl3 in female livers and AML12 cells in a time- and androgen receptor-dependent manner. |
Bmal1 knockout mice; ChIP assay for NR1D1 binding at Elovl3 promoter across circadian time; castration experiments; 5α-dihydrotestosterone injection in female mice; flutamide (androgen receptor antagonist) treatment in AML12 cells; zeitgeber/circadian time series mRNA analysis |
The Journal of biological chemistry |
High |
30862677
|
| 2021 |
ELOVL3 ablation reduces meibum melting temperature by ~8°C and increases meibum fluidity, demonstrating that ELOVL3-derived VLCFAs determine the thermotropic/physical properties of meibum; transcriptomic analysis of meibomian glands reveals that ELOVL3 loss dysregulates lipid biosynthesis, inflammation, and stress response gene networks. |
Elovl3 knockout mice; heat-stage polarized light microscopy for meibum melting temperature; histological examination; MG transcriptome analysis (RNA-seq); slit lamp examination |
FASEB journal |
Medium |
33455016
|
| 2023 |
ZHX2 (zinc fingers and homeoboxes 2) transcription factor positively regulates Elovl3 expression in mouse liver; forced Elovl3 expression in human hepatoma cells reduces cell growth and causes cell cycle arrest in S-phase with reduced cyclin mRNA levels, demonstrating that ELOVL3-derived VLCFAs regulate hepatocyte proliferation and cell cycle progression. |
Mouse microarray and in vivo liver regeneration models; cell-based Elovl3 overexpression in hepatoma lines; cell growth assays; cell synchronization and cell cycle analysis; cyclin mRNA measurement; VLCFA profiling; Zhx2-null mouse livers |
American journal of physiology. Gastrointestinal and liver physiology |
Medium |
37847682
|
| 2023 |
Hepatic-specific deletion of Elovl3 (via Cre/LoxP) does not alter body weight, liver mass, liver triglyceride content, lipid profiles, or hepatic lipogenic/oxidative gene expression under normal chow or high-fat diet, demonstrating that hepatic ELOVL3 alone is dispensable for liver lipid homeostasis (negative finding; the anti-obesity phenotype in global KO is attributable to extrahepatic ELOVL3 function). |
Liver-specific Elovl3 Cre/LoxP knockout mice; high-fat diet challenge; body weight and liver mass measurement; lipidomics; liver triglyceride assay; hepatic gene expression (qRT-PCR and Western blot); glucose tolerance test; ELOVL1 and ELOVL7 expression controls |
Biochemical and biophysical research communications |
Medium |
37030067
|
| 2024 |
Testosterone/androgen receptor (AR) negatively regulates ELOVL3 transcription through an androgen response element (ARE) in the ELOVL3 promoter; AR overexpression suppresses ELOVL3 promoter activity, and ELOVL3 knockdown reduces lipid droplet accumulation and FASN expression while increasing ATGL mRNA in porcine preadipocytes. |
Porcine preadipocyte model with testosterone treatment; transcriptomic sequencing; dual-luciferase reporter assay with wild-type and ARE-mutant ELOVL3 promoter; AR overexpression; ELOVL3 siRNA knockdown; lipid droplet staining; FASN and ATGL mRNA analysis |
Animals |
Medium |
39123669
|
| 2025 |
BAT-specific deletion of Elovl3 causes cold intolerance due to impaired BAT thermogenesis and defective mitochondrial cristae remodeling; lipidomics reveals that Elovl3 deficiency markedly reduces lysophosphatidylcholine, cardiolipin, and acylcarnitine levels in BAT, identifying ELOVL3-derived VLCFAs as required components of BAT phospholipid homeostasis that support UCP1 expression and mitochondrial remodeling during cold adaptation. |
BAT-specific Elovl3 Cre/LoxP knockout mice; cold exposure challenge; body temperature measurement; Ucp1 expression (qRT-PCR and Western blot); BAT histology; lipidomics analysis; mitochondrial ultrastructure (histological evaluation of cristae remodeling); muscle shivering assessment |
Journal of lipid research |
High |
41202879
|
| 2026 |
USP25 deubiquitinase binds and stabilizes PARP1 through deubiquitination; PARP1 in turn promotes preadipocyte differentiation and maturation by regulating ELOVL3 expression, placing ELOVL3 downstream of a USP25–PARP1 axis in adipocyte differentiation. |
Usp25 knockout mice; 3T3-L1 adipocyte differentiation model; RNA sequencing; Co-immunoprecipitation of USP25 and PARP1; ubiquitination assay; PARP1 knockdown with Elovl3 expression readout; adipose tissue histology |
Journal of lipid research |
Medium |
41692245
|