Affinage

ANGPTL4

Angiopoietin-related protein 4 · UniProt Q9BY76

Length
406 aa
Mass
45.2 kDa
Annotated
2026-06-09
100 papers in source corpus 43 papers cited in narrative 44 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ANGPTL4 is a secreted, PPAR-regulated glycoprotein that governs the partitioning of circulating lipids across tissues by acting as a context-dependent inhibitor of lipoprotein lipase (LPL) (PMID:10862772, PMID:17761937). Originally identified as a fasting-induced, PPARα/γ transcriptional target whose plasma levels track nutritional state (PMID:10862772), it is processed after secretion into an oligomeric N-terminal domain and a fibrinogen-like C-terminal domain, with N-terminal oligomerization—not proprotein-convertase cleavage—being required for LPL inhibition; the E40K variant is processed normally but fails to form extracellular oligomers and cannot inhibit LPL (PMID:19270337). Mechanistically, ANGPTL4 binds LPL near the catalytic cavity and triggers cooperative, irreversible unfolding of the α/β-hydrolase domain, converting active endothelial-bound LPL dimers to inactive monomers and raising plasma triglycerides (PMID:17761937, PMID:34336854); this destabilizing action is opposed allosterically by APOC2 and physically by GPIHBP1, which protect LPL from unfolding (PMID:34336854, PMID:37094117). The inhibitory activity is tuned by complex formation with ANGPTL8, which yields a far weaker LPL inhibitor and, under insulin/feeding, locally preserves adipose LPL activity to direct fatty acids toward fat storage (PMID:32487544, PMID:34801488). Tissue-specific deletion studies establish adipocyte-derived ANGPTL4 as the dominant regulator of plasma triglyceride partitioning, with adipose, brown-fat, and hepatocyte loss each enhancing local lipase activity, accelerating triglyceride clearance, and improving glucose homeostasis (PMID:29563332, PMID:29627378, PMID:34255741, PMID:33846453), and human genetic mimicry confirms that ANGPTL4 modulates plasma lipids essentially exclusively through LPL in humans (PMID:36372100). Beyond lipase control, ANGPTL4 mediates glucocorticoid-induced insulin resistance via a ceramide–PP2A/PKCζ axis (PMID:28743803, PMID:31053639), acts in the hypothalamus to suppress AMPK, food intake, and to raise energy expenditure (PMID:20798332), and signals through integrins and other surface partners in disease contexts including kidney fibrosis (Integrin β1) (PMID:39630889), cancer invasion and metabolism (Integrin α5β1, IQGAP1, ESM1) (PMID:28641978, PMID:39647634, PMID:38212795), and macrophage lipid handling via CD36/ABCA1 (PMID:27460411). Its expression is integrated by a broad set of upstream regulators—HIF-1α, PPARβ/δ, RORα, NFAT, TAZ/YAP, SMAD3, and FOXO1—often acting through intronic and promoter cis-regulatory modules, including one suppressed by gut microbiota in the intestine (PMID:12099716, PMID:22479192, PMID:31434807, PMID:31641008, PMID:32686149, PMID:31428774, PMID:38643448, PMID:39633372).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 High

    Established ANGPTL4 as a nutritionally regulated secreted factor under direct PPAR control, framing it as an endocrine effector in metabolism.

    Evidence Subtractive hybridization, plasma Western blotting, and PPARα-null mice

    PMID:10862772

    Open questions at the time
    • Did not define a molecular target or downstream pathway
    • Endocrine action site unspecified
  2. 2002 Medium

    Showed ANGPTL4 induction is not exclusive to PPAR signaling, identifying hypoxia/HIF-1α as an independent transcriptional input.

    Evidence Adenoviral HIF-1α overexpression and hypoxia mimetics in rat cardiomyocytes

    PMID:12099716

    Open questions at the time
    • HIF-1α binding site not mapped
    • Functional consequence in cardiac tissue unaddressed
  3. 2004 High

    Resolved the existence of full-length versus cleaved circulating ANGPTL4 and located a functional PPAR response element in intron 3, refining how the gene is transcriptionally and post-translationally regulated.

    Evidence ChIP, EMSA, transactivation, and plasma protein analysis across cell/tissue types

    PMID:15190076

    Open questions at the time
    • Functional role of cleavage products not yet determined
    • Protease identity not established here
  4. 2007 High

    Defined the core physiological mechanism: ANGPTL4 inhibits triglyceride clearance by converting endothelial LPL dimers to inactive monomers.

    Evidence Angptl4-transgenic mice with post-heparin LPL activity and lipoprotein clearance assays

    PMID:17761937

    Open questions at the time
    • Molecular basis of dimer-to-monomer conversion not resolved
    • Reversibility unknown
  5. 2009 High

    Determined that N-terminal oligomerization, not proprotein cleavage, drives LPL inhibition and explained the E40K loss-of-function variant.

    Evidence HEK-293A expression, oligomerization and LPL inhibition assays, E40K mutant, parallel mouse work

    PMID:19270337

    Open questions at the time
    • Atomic-level LPL contact sites not defined
    • Stoichiometry of the inhibitory oligomer unclear
  6. 2010 High

    Extended ANGPTL4 function to central energy balance, placing it upstream of hypothalamic AMPK to control food intake and energy expenditure.

    Evidence ICV ANGPTL4, Angptl4-null mice, AMPK activity assays, metabolic cages

    PMID:20798332

    Open questions at the time
    • Hypothalamic receptor mediating AMPK suppression not identified
  7. 2012 High

    Dissected tissue-specific cis-regulation and revealed gut microbiota as a suppressor of intestinal ANGPTL4, linking the microbiome to fat storage.

    Evidence Zebrafish transgenic reporters, module mutagenesis, gnotobiotic colonization; plus PPARβ/δ ChIP-Seq in cancer cells

    PMID:22479192 PMID:23208498

    Open questions at the time
    • Microbial signal acting on the intestinal module not fully defined
    • Cross-species generalization of modules incomplete
  8. 2013 Medium

    Showed butyrate induces intestinal ANGPTL4 through a PPARγ-independent upstream element additive to PPAR signaling, expanding the regulatory logic.

    Evidence Reporter assays, PPAR agonist/antagonist, germ-free mice colonized with C. tyrobutyricum, butyrate gavage

    PMID:23518684

    Open questions at the time
    • Transcription factor binding the butyrate-responsive element not identified
  9. 2017 High

    Connected ANGPTL4 to glucocorticoid-induced insulin resistance via a ceramide–PP2A/PKCζ signaling axis, and mapped the integrin α5β1 binding role of the C-terminal domain in cancer.

    Evidence Angptl4-null mice with metabolomics and pathway inhibitors; integrin binding and functional assays with T266M mutant

    PMID:28641978 PMID:28743803

    Open questions at the time
    • How adipose-derived lipolysis links to hepatic ceramide synthesis mechanistically incomplete
    • Integrin signaling intermediates only partially defined
  10. 2018 High

    Provided structural and tissue-resolved understanding: crystal structures of the C-terminal domain, adipose/BAT-specific deletion phenotypes, and a muscle role in exercise-induced AMPK activation.

    Evidence X-ray crystallography; adipose- and BAT-specific Angptl4 KO mice; treadmill and myotube AMPK/ACC assays

    PMID:29563332 PMID:29627378 PMID:29713054 PMID:29952246

    Open questions at the time
    • Structures cover only the fibrinogen-like domain, not the inhibitory N-terminal oligomer
    • Muscle ANGPTL4 receptor undefined
  11. 2019 High

    Defined the biophysical inhibition mechanism (cooperative LPL unfolding opposed by GPIHBP1) and broadened ANGPTL4 into ferroptosis, macrophage polarization, podocyte injury, and lipogenesis pathways under diverse upstream regulators.

    Evidence HDX-MS and LPL stability assays; TAZ/NOX2 ferroptosis assays; RORα ChIP in MSCs; NFAT ChIP in podocytes; isotope-labeled lipogenesis in Angptl4-null mice; PPARβ/δ transcription-initiation ChIP/MS

    PMID:31053639 PMID:31428774 PMID:31434807 PMID:31641008 PMID:34336854

    Open questions at the time
    • Whether non-LPL roles share a common receptor mechanism is unresolved
    • Surface receptors for ferroptosis and macrophage effects unidentified
  12. 2020 High

    Established the ANGPTL4/8 complex as a feeding-responsive switch that dampens LPL inhibition, and validated fasting regulation and additional disease roles in humans and mice.

    Evidence Serum complex immunoassays, recombinant LPL-inhibition kinetics, insulin-treated adipocytes; human fasting biopsies; pancreatitis and CRC metastasis models

    PMID:32487544 PMID:32504883 PMID:32638512 PMID:32641980 PMID:32686149

    Open questions at the time
    • Structural basis of the ANGPTL4/8 interaction not resolved
    • Receptor for non-lipase disease effects still unknown
  13. 2021 High

    Mapped tissue source hierarchy and target specificity: hepatocyte/adipocyte ANGPTL4 effects, endothelial lipase inhibition modulated by ANGPTL8, and human genetic evidence that ANGPTL4 acts through LPL essentially exclusively.

    Evidence Hepatocyte- and adipocyte-specific KO mice with ASO pharmacology; recombinant EL-inhibition assays; UK Biobank/European cohort genetic mimicry

    PMID:33846453 PMID:34255741 PMID:34504977 PMID:34801488 PMID:36372100

    Open questions at the time
    • Reconciliation of in vitro EL/HL inhibition with human LPL-exclusive genetics incomplete
    • Tissue-specific protease processing not fully characterized
  14. 2023 High

    Refined the allosteric model by showing APOC2 and ANGPTL4 bind overlapping LPL sites with opposite conformational effects, and identified a protective vascular smooth-muscle role of ANGPTL4 protein.

    Evidence HDX-MS competition and thermal stability assays; ANGPTL4 protein injection in Apoe-/- mice with SMC phenotyping

    PMID:36782020 PMID:37094117

    Open questions at the time
    • How physiological APOC2/ANGPTL4 ratios set net LPL activity unresolved
    • SMC-protective signaling receptor undefined
  15. 2024 Medium

    Linked circulating C-terminal ANGPTL4 fragments to cardiovascular outcomes and expanded receptor-mediated functions to kidney fibrosis (Integrin β1), prostate cancer metabolism (IQGAP1), ovarian cancer signaling (ESM1, JAK2/STAT3), and FOXO1-driven cardiomyocyte senescence.

    Evidence Large LURIC/getABI cohorts plus GPIHBP1-LPL recombinant assays; cell-type-specific KO mice; Co-IP/GST pull-down for IQGAP1, ESM1, Integrin β1; ChIP-qPCR for FOXO1/SMAD3

    PMID:38212795 PMID:38643448 PMID:39392008 PMID:39630889 PMID:39633372 PMID:39647634

    Open questions at the time
    • Many partner interactions rest on single-lab Co-IP without reciprocal in vivo validation
    • Whether integrin/IQGAP1/ESM1 binding share a common structural interface unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The unifying receptor logic linking ANGPTL4's secreted, non-LPL signaling activities (integrins, IQGAP1, ESM1, hypothalamic AMPK, ferroptosis) to defined surface receptors and a high-resolution structure of the inhibitory N-terminal oligomer bound to LPL remain unresolved.
  • No structure of the N-terminal oligomer–LPL complex
  • No single receptor reconciling diverse signaling roles
  • Physiological relevance of EL/HL inhibition versus LPL-exclusive human genetics unsettled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0048018 receptor ligand activity 4 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005576 extracellular region 4 GO:0005886 plasma membrane 3
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1430728 Metabolism 5 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4
Partners
ANGPTL8APOC2ESM1GPIHBP1IQGAP1ITGA5ITGB1LPL
Complex memberships
ANGPTL4/8 complex

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 ANGPTL4 (FIAF) is a direct transcriptional target of PPARα and PPARγ. It is secreted into blood plasma, and its plasma levels increase with fasting and decrease with chronic high-fat feeding, indicating an endocrine function in metabolic regulation. Subtractive hybridization (SABRE), Western blotting of plasma, PPARα-null mouse model The Journal of biological chemistry High 10862772
2002 Hypoxia induces ANGPTL4 (PGAR) expression in cardiomyocytes via HIF-1α, not via the PPARα/RXR pathway, as demonstrated by adenoviral overexpression of HIF-1α and pharmacological hypoxia mimetics. Adenoviral HIF-1α overexpression, CoCl2/desferrioxamine treatment, RT-PCR in neonatal rat cardiomyocytes Journal of molecular and cellular cardiology Medium 12099716
2004 ANGPTL4 (FIAF) is present in human and mouse blood plasma in both a full-length and a truncated (cleaved) form. Differentiated 3T3-L1 adipocytes produce truncated FIAF, human liver produces truncated FIAF, and fenofibrate (PPARα agonist) treatment increases circulating truncated FIAF but not native FIAF. A functional PPAR response element was identified within intron 3 of the FIAF gene. Western blotting of plasma, chromatin immunoprecipitation (ChIP), gel shift/EMSA, transactivation assays, cell differentiation experiments The Journal of biological chemistry High 15190076
2007 ANGPTL4 overexpression in mice inhibits LPL-dependent plasma triglyceride clearance by converting endothelial-bound LPL dimers to circulating LPL monomers, thereby reducing LPL activity and impairing cholesterol/fatty acid uptake into tissues, which secondarily upregulates hepatic cholesterol and fatty acid synthesis pathways. Angptl4-transgenic mouse model, post-heparin LPL activity assays, isotopic lipoprotein clearance studies Arteriosclerosis, thrombosis, and vascular biology High 17761937
2009 ANGPTL4 forms dimers and tetramers intracellularly prior to secretion. After secretion, it is cleaved at a proprotein convertase site (RRKR161-164), releasing an oligomeric N-terminal domain and a monomeric C-terminal fibrinogen-like domain. Oligomerization (not cleavage) is required for LPL inhibition. The E40K variant is synthesized and processed normally but fails to accumulate as extracellular oligomers and cannot inhibit LPL activity. HEK-293A cell expression, oligomerization assays, LPL inhibition assays, proprotein convertase inhibition, E40K mutant analysis, parallel mouse experiments The Journal of biological chemistry High 19270337
2010 Hypothalamic ANGPTL4 suppresses food intake and increases energy expenditure by inhibiting hypothalamic AMPK activity. Intracerebroventricular administration of ANGPTL4 suppresses food intake and body weight gain; Angptl4-null mice show increased hypothalamic AMPK activity, increased food intake, and decreased energy expenditure. Intracerebroventricular (ICV) ANGPTL4 injection, Angptl4-null mouse model, AMPK activity assays, metabolic cage measurements Diabetes High 20798332
2012 Discrete tissue-specific cis-regulatory modules within ANGPTL4 intron 3 drive expression in the liver, pancreatic islet β-cells, and intestinal enterocytes. The microbiota suppresses the transcriptional activity of the intestine-specific regulatory module, reducing intestinal ANGPTL4 expression and thereby modulating peripheral fat storage. Zebrafish in vivo transgenic reporter assays, site-directed mutagenesis of regulatory modules, gnotobiotic zebrafish colonization experiments PLoS genetics High 22479192
2012 PPARβ/δ drives ANGPTL4 transcription; synthetic inverse agonists of PPARβ/δ suppress ANGPTL4 expression and secretion by inducing a dominant transcriptional repressor complex at the ANGPTL4 transcription initiation site via a non-canonical, HDAC-independent mechanism. Suppression of ANGPTL4 transcription is functionally linked to reduced cancer cell invasion into 3D matrices. ChIP-Seq, microarray, inverse agonist treatment, ANGPTL4 knockdown, recombinant ANGPTL4 rescue, 3D invasion assays Oncogene High 23208498
2013 Butyrate induces intestinal ANGPTL4 expression independently of PPARγ, using a butyrate-responsive element ~0.5 kb upstream of the transcription start site, while PPARγ agonists act via a distinct PPAR-responsive element downstream of the transcription start site; the two pathways are additive. PPARγ-independent reporter assays, PPAR agonist/antagonist treatment, germ-free mouse colonization with Clostridium tyrobutyricum, butyrate gavage American journal of physiology. Gastrointestinal and liver physiology Medium 23518684
2015 Adipose ANGPTL4 is upregulated via PPARγ activation following glucagon receptor antagonist treatment and promotes α-cell proliferation specifically; glucagon receptor antagonist fails to induce α-cell proliferation in Angptl4-knockout mice, placing ANGPTL4 on the pathway linking adipose lipid metabolism to pancreatic α-cell expansion. Angptl4 knockout mice, glucagon receptor antagonist treatment, Angptl4 supplementation, adipose PPARγ activation assays Proceedings of the National Academy of Sciences of the United States of America Medium 26621734
2016 Haematopoietic ANGPTL4 deficiency in macrophages promotes foam cell formation by enhancing CD36 expression and reducing ABCA1 surface localization, and increases common myeloid progenitor expansion (higher lipid raft content, increased proliferation, decreased apoptosis), leading to larger atherosclerotic plaques with bigger necrotic cores. Bone marrow transplantation (haematopoietic-specific KO), flow cytometry, CD36 and ABCA1 localization assays, atherosclerotic lesion analysis in hyperlipidemic mice Nature communications High 27460411
2017 ANGPTL4 mediates glucocorticoid-induced insulin resistance by promoting lipolysis in white adipose tissue, increasing hepatic ceramide concentrations (by inducing ceramide synthetic pathway enzymes), and activating PP2A and PKCζ downstream of ceramide. Angptl4-null mice are protected from glucocorticoid-induced glucose intolerance. Angptl4-knockout mouse model, metabolomic profiling, pharmacological inhibition of ceramide synthesis (myriocin) and PKCζ, PP2A/PKCζ activity assays Science signaling High 28743803
2018 Crystal structures of the fibrinogen-like (C-terminal) domains of ANGPTL4 and ANGPTL3 were solved, providing structural insights into known loss-of-function mutations and the mechanism of action of these proteins. X-ray crystallography Scientific reports High 29713054
2018 Adipose tissue-specific deletion of ANGPTL4 results in enhanced LPL activity, rapid clearance of circulating TAGs, increased adipose lipolysis and FA oxidation, decreased FA synthesis, prevention of ectopic lipid deposition in liver and muscle, reduced nPKC membrane translocation, improved insulin signaling and glucose tolerance, and attenuated atherosclerosis. Adipose-specific Angptl4 knockout mice, LPL activity assays, metabolic turnover studies, nPKC translocation assays, glucose tolerance tests, atherosclerosis lesion analysis JCI insight High 29563332
2018 Brown adipose tissue (BAT)-specific deletion of ANGPTL4 results in enhanced LPL activity, increased circulating TAG clearance, increased FA oxidation, reduced FA synthesis, improved glucose tolerance, and enhanced thermogenesis during acute cold exposure. BAT-specific Angptl4 knockout mice, LPL activity assays, metabolic measurements, cold exposure experiments Molecular metabolism High 29627378
2019 In mesenchymal stem cells (MSCs), ANGPTL4 expression is induced by RORα in response to inflammatory mediators (IL-1β). Secreted ANGPTL4 from MSCs suppresses macrophage polarization toward a proinflammatory phenotype; ANGPTL4-deficient MSCs fail to inhibit inflammatory macrophage polarization. Exogenous ANGPTL4 protein improves cardiac function following myocardial infarction. MSC-macrophage co-culture, ANGPTL4-deficient MSCs, RORα overexpression, ChIP showing RORα binding to ANGPTL4 promoter, peritonitis and MI animal models JCI insight High 31434807
2019 ANGPTL4 deficiency in macrophages increases lipid uptake and cellular respiration without affecting LPL protein levels. Low levels of N-terminal ANGPTL4 (in hypomorphic mice) mitigate chylous ascites and acute-phase response compared with complete ANGPTL4 absence during high-fat feeding. Angptl4-knockout and Angptl4-hypomorphic mouse models, macrophage lipid uptake assays, LPL protein level measurement, respiratory assays, serum amyloid A measurement Journal of lipid research High 31409739
2019 ANGPTL4 is a direct transcriptional target of TAZ (Hippo pathway effector) and sensitizes ovarian cancer cells to ferroptosis by activating NOX2 (NADPH oxidase 2). TAZ removal confers ferroptosis resistance; TAZS89A overexpression sensitizes cells; ANGPTL4 loss abolishes TAZ-mediated ferroptosis sensitization. TAZ knockdown and overexpression, ANGPTL4 knockdown, genomic integration/transcriptomics, ferroptosis assays Molecular cancer research : MCR Medium 31641008
2019 ANGPTL4 inhibits LPL by triggering cooperative and sequential unfolding of LPL's α/β-hydrolase domain, resulting in irreversible collapse of the catalytic cavity. GPIHBP1 binding to LPL protects against ANGPTL4-mediated unfolding. Hydrogen-deuterium exchange/mass spectrometry, LPL thermal stability assays, GPIHBP1 protection assays (reviewed in detail in 2021 paper PMID:34336854 which cites earlier work) Frontiers in cell and developmental biology High 34336854
2020 ANGPTL8 forms complexes with ANGPTL4; the ANGPTL4/8 complex has >100-fold less LPL-inhibitory activity than ANGPTL4 alone (while ANGPTL3/8 is >100-fold more potent than ANGPTL3). Insulin increases ANGPTL4/8 secretion from adipocytes during feeding, locally blocking ANGPTL4-mediated LPL inhibition in adipose tissue, thereby directing FA toward fat rather than muscle. Immunoassay quantification of complexes in human serum, recombinant protein LPL-inhibitory activity assays, competition experiments, insulin treatment of hepatocytes and adipocytes Journal of lipid research High 32487544
2020 Fasting increases ANGPTL4 mRNA and protein levels in human adipose tissue and plasma, concurrent with decreased LPL activity (-60%), while LPL mRNA and protein remain unchanged. Decreased plasma insulin (which downregulates ANGPTL4 in primary human adipocytes) and increased cortisol and free fatty acids (which upregulate ANGPTL4) are the hormonal mediators. Human adipose tissue biopsies (fasting/fed), LPL activity assays, primary human adipocyte culture with insulin/cortisol/fatty acid treatments, plasma ANGPTL4 ELISA Molecular metabolism High 32504883
2020 ANGPTL4 depletion in CRC cells significantly inhibited c-Jun-mediated transactivation of NOX4 expression, reducing ROS, MMP-1, and MMP-9 levels and disrupting oleic acid-promoted CRC metastasis in vitro and in vivo. ANGPTL4 knockdown, NOX4 reporter/luciferase assays, ROS measurement, MMP knockdown, in vivo tumor metastasis assay Theranostics Medium 32641980
2021 Hepatocyte-specific Angptl4 deficiency facilitates catabolism of TAG-rich lipoprotein remnants via increased hepatic lipase (HL) activity, significantly reducing circulating TAG and cholesterol. Loss of hepatic Angptl4 also promotes FA uptake, FA oxidation, ROS production, and AMPK activation. Liver-targeted pharmacologic inhibition of Angptl4 recapitulates these effects. Hepatocyte-specific Angptl4 mutant mice, metabolic turnover studies, HL activity assays, FA oxidation measurements, AMPK activation assays, liver-targeted ASO pharmacology The Journal of clinical investigation High 34255741
2021 ANGPTL4 is an inhibitor of endothelial lipase (EL) and is a more potent EL inhibitor than ANGPTL3. Formation of the ANGPTL4/8 complex reduces EL-inhibitory activity of ANGPTL4, in contrast to ANGPTL3/8 which increases EL-inhibitory activity of ANGPTL3. Recombinant ANGPTL protein EL-inhibitory activity assays, comparison of complex vs. free forms Heliyon Medium 34504977
2021 Genetic mimicry analysis in humans shows that ANGPTL4 suppression is highly concordant with LPL enhancement but not with HL or EL, demonstrating that ANGPTL4 modulates plasma metabolic parameters exclusively via LPL in humans. Human genetics/genetic mimicry analysis using UK Biobank (>110,000 participants) and 11 European cohorts; comparison of metabolic trait profiles for ANGPTL4 vs. LPL, LIPC, LIPG variants Journal of lipid research High 36372100
2021 ANGPTL4 inhibits LPL by promoting unfolding of LPL's hydrolase domain, leading to irreversible cleavage and degradation of LPL. ANGPTL8 binding to ANGPTL4 reduces this inhibitory activity, keeping LPL active in adipose tissue after feeding. Review synthesizing LPL unfolding studies, ANGPTL4/ANGPTL8 interaction studies, and tissue-specific LPL activity measurements (cited mechanistic studies) Journal of lipid research High 34801488
2021 Adipocyte-specific ANGPTL4 deficiency recapitulates the triglyceride phenotype of whole-body deficiency (increased adipose LPL activity, lower plasma TG, increased adipose TAG uptake), confirming adipocyte-derived ANGPTL4 as the primary source regulating plasma TG partitioning under normal diet conditions. Adipocyte-specific Angptl4 knockout mice (HFD and normal diet), LPL activity assays, triglyceride clearance and uptake assays, glucose homeostasis measurements Scientific reports Medium 33846453
2019 Chronic dexamethasone (glucocorticoid) treatment induces an ANGPTL4-ceramide-PKCζ axis that activates hepatic de novo lipogenesis and triglyceride synthesis. Myriocin (ceramide synthesis inhibitor) and PKCζ inhibitor both reduce dexamethasone-induced lipid disorders in WT but not Angptl4-null mice, placing ceramide-PKCζ downstream of ANGPTL4. Stable isotope labeling for hepatic lipogenesis, Angptl4-null mice, myriocin treatment, AAV-shRNA targeting Sptlc2, PKCζ inhibitor (ACPD) treatment The Journal of biological chemistry High 31053639
2020 ANGPTL4 exacerbates pancreatitis by activating macrophage infiltration via PI3K/AKT signaling, increasing complement component 5a (C5a) levels, which activates C5a receptor leading to hypercytokinemia and acinar cell damage. ANGPTL4 deficiency or neutralizing antibody mitigates pancreatitis severity. Angptl4 knockout mice, neutralizing antibody treatment, exogenous ANGPTL4 administration, C5a neutralizing antibody, LPS-activated macrophage assays, PI3K/AKT inhibition EMBO molecular medicine Medium 32638512
2020 Calcineurin (CaN) inhibitors protect against PAN-induced podocyte injury by inhibiting NFAT (Nfatc1), which directly binds the Angptl4 promoter to drive Angptl4 expression. ANGPTL4 overexpression in podocytes induces cytoskeletal rearrangement, reduces synaptopodin, and enhances apoptosis. PAN-induced MCD rat model, CaN inhibitor treatment, Nfatc1 overexpression/knockdown, ChIP assay (Nfatc1 binding to Angptl4 promoter), ANGPTL4 overexpression/knockdown in podocytes The Journal of pathology High 32686149
2021 G protein-coupled estrogen receptor (GPER) stimulates trophoblast cell invasion by activating YAP (Hippo pathway effector) via an MST1-independent mechanism, which in turn drives ANGPTL4 expression. ANGPTL4 is required for GPER-stimulated trophoblast invasion. GPER agonist (G1) treatment, RNA-seq, YAP pharmacological inhibitors, loss- and gain-of-function experiments, Transwell invasion assays Communications biology Medium 34773076
2023 APOC2 and ANGPTL4 bind overlapping sites on LPL (regions surrounding the catalytic pocket and lid-anchoring structures), but have opposite effects on LPL conformation: ANGPTL4 destabilizes lid-anchoring structures promoting LPL inactivation, while APOC2 stabilizes them and increases LPL thermal stability. Hydrogen-deuterium exchange/mass spectrometry (HDX-MS), LPL thermal stability assays, competition binding experiments Proceedings of the National Academy of Sciences of the United States of America High 37094117
2024 Recombinant protein assays demonstrate that ANGPTL3/8 complex potently inhibits GPIHBP1-bound LPL activity. CD-ANGPTL4 (C-terminal domain-containing fragment generated by furin or plasmin cleavage) is positively associated with cardiovascular mortality and inflammation in two large cohort studies; ANGPTL4/8 complex formation converts ANGPTL4 from a furin substrate to a plasmin substrate. Recombinant protein GPIHBP1-LPL activity assays, dedicated immunoassays in LURIC (n=2394) and getABI (n=6188) cohorts, cardiovascular mortality follow-up Circulation High 39392008
2024 Both podocyte- and tubule-derived ANGPTL4 are fibrogenic in diabetic kidneys. Secreted ANGPTL4 from these cells interacts with Integrin β1 and influences the association between DPP-4 and Integrin β1. ANGPTL4 mutant mice are protected from diabetes-accelerated fibrosis, showing reduced STING pathway activation, reduced EMT/EndoMT, and increased FA oxidation. Podocyte- and tubule-specific ANGPTL4 mutant mice, diabetic mouse model, Co-IP (ANGPTL4-Integrin β1), DPP-4/Integrin β1 association assays, kidney-targeted pharmacologic inhibition Science advances High 39630889
2023 In atherosclerotic mice, ANGPTL4 protein treatment inhibits phenotypic transition of vascular smooth muscle cells into macrophage-like cells by downregulating NOX1 (NADPH oxidase 1) activation of KLF4, reducing KLF4-mediated SMC dedifferentiation and stabilizing atherosclerotic plaques. ANGPTL4 protein injection in Apoe-/- atherosclerotic mice, SMC isolation and phenotype analysis, NOX1 and KLF4 expression assays, fibrous cap thickness measurements Experimental & molecular medicine Medium 36782020
2024 ANGPTL4 activates JAK2/STAT3 signaling in ovarian cancer cells to promote proliferation and invasion. ANGPTL4 also interacts with ESM1, which promotes ANGPTL4 binding to LPL (reprogramming lipid metabolism), and interferes with ANGPTL4 binding to integrin and VE-cadherin (stabilizing vascular integrity to promote angiogenesis). RNA-seq, Co-IP, molecular docking, MTT/EdU/wound healing/transwell assays, xenograft model, CAM assay, zebrafish model, Western blot for JAK2-STAT3 pathway Journal of translational medicine Medium 38212795
2019 PPARβ/δ inverse agonist PT-S264 impairs ANGPTL4 transcription initiation by decreasing recruitment of activating Mediator subunits, RNA polymerase II, and TFIIB (but not TFIIA) to the ANGPTL4 promoter. NCOR is the main PT-S264-dependent interactor of PPARβ/δ, identified by mass spectrometry. ChIP for Mediator/PolII/TFIIB/TFIIA at ANGPTL4 promoter, mass spectrometry of PPARβ/δ interactors, PPARβ/δ basal-repression mutant reconstitution in KO cells Nucleic acids research High 31428774
2021 In macrophage foam cells, ANGPTL4 deficiency promotes foam cell formation through enhanced CD36 expression and reduced surface ABCA1; in macrophages, recombinant ANGPTL4 decreases lipid uptake. ANGPTL4 deficiency does not alter LPL protein levels in macrophages (negative finding for that specific mechanism). Recombinant ANGPTL4 treatment of macrophages, ANGPTL4-deficient macrophage lipid uptake assays, CD36/ABCA1 localization, LPL protein measurement Nature communications / Journal of lipid research Medium 27460411 31409739
2018 Angptl4 is required for exercise-induced AMPK activation in skeletal muscle. Angptl4 treatment of C2C12 myotubes increases AMPK and ACC phosphorylation and mitochondrial maximum respiratory capacity. Exercise-induced AMPK and ACC phosphorylation is attenuated in Angptl4-knockout mice, and endurance is reduced. Treadmill exercise in Angptl4-knockout vs. WT mice, recombinant Angptl4 treatment of myotubes, AMPK/ACC phosphorylation assays, Seahorse respirometry Journal of applied physiology Medium 29952246
2024 TGF-β1 secreted by adipose-derived stem cells (ADSCs) activates SMAD3 in CRC cells, and SMAD3 directly binds the ANGPTL4 promoter (shown by ChIP) to drive ANGPTL4 transcription, which promotes glycolysis and anoikis resistance in CRC cells. RNA sequencing, ChIP assay (SMAD3 binding to ANGPTL4 promoter), co-culture experiments, in vivo intraperitoneal seeding model Cellular and molecular life sciences : CMLS Medium 38643448
2022 Angptl4 regulates monocyte differentiation to macrophages during wound healing via a novel Angptl4-ifi202b axis. In Angptl4-deficient wounds, ifi202b is elevated and monocyte-to-macrophage transition is impaired. An unbiased kinase inhibitor screen revealed an Angptl4-mediated kinome network involving S6K, JAK, and CDK that modulates ifi202b expression. Silencing ifi202b in Angptl4-deficient monocytes rescues impaired monocyte-to-macrophage transition. Angptl4-knockout mice, single-cell RNA sequencing, flow cytometry, kinase inhibitor screen, ifi202b knockdown rescue experiments Cell death & disease Medium 35210411
2024 CAF-derived ANGPTL4 binds to IQGAP1 on PCa cell membranes, activating the Raf-MEK-ERK-PGC1α axis to promote mitochondrial biogenesis and OXPHOS metabolism, facilitating prostate cancer growth and chemoresistance. Proteomic analysis of conditioned media, GST pull-down, Co-IP (ANGPTL4-IQGAP1), metabolomics, drug screening (QGGP as IQGAP1 inhibitor) Journal of advanced research Medium 39647634
2017 The ANGPTL4 T266M variant in the C-terminal domain binds integrin α5β1 with reduced affinity compared to wild-type, leading to weaker activation of downstream signaling molecules, impaired tumor cell proliferation, anoikis resistance, and migratory capability. C-terminal ANGPTL4 also regulates Glut2 expression. Integrin α5β1 binding assays, signaling pathway analysis (downstream of integrin), proliferation/anoikis/migration assays, Glut2 expression measurement Biochimica et biophysica acta. Molecular cell research Medium 28641978
2024 SGLT2 inhibitor (SGLT2i) reduces ANGPTL4 expression by regulating the upstream transcription factor FOXO1, which directly drives ANGPTL4 transcription under hyperglycemia/hyperlipidemia conditions. ANGPTL4 knockdown reduces cardiomyocyte senescence; ANGPTL4 overexpression worsens it. ChIP-qPCR confirms FOXO1 binding to the ANGPTL4 promoter. DCM mouse model, AC16 human cardiomyocyte model, ANGPTL4 knockdown/overexpression, RNA-seq, ChIP-qPCR (FOXO1 binding to ANGPTL4 promoter), SGLT2i treatment Cardiovascular diabetology Medium 39633372

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene. The Journal of biological chemistry 477 10862772
2016 Inactivating Variants in ANGPTL4 and Risk of Coronary Artery Disease. The New England journal of medicine 419 26933753
2016 Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease. The New England journal of medicine 415 26934567
2019 A TAZ-ANGPTL4-NOX2 Axis Regulates Ferroptotic Cell Death and Chemoresistance in Epithelial Ovarian Cancer. Molecular cancer research : MCR 262 31641008
2004 The direct peroxisome proliferator-activated receptor target fasting-induced adipose factor (FIAF/PGAR/ANGPTL4) is present in blood plasma as a truncated protein that is increased by fenofibrate treatment. The Journal of biological chemistry 227 15190076
2014 Regulation of lipoprotein lipase by Angptl4. Trends in endocrinology and metabolism: TEM 166 24397894
2007 Angptl4 upregulates cholesterol synthesis in liver via inhibition of LPL- and HL-dependent hepatic cholesterol uptake. Arteriosclerosis, thrombosis, and vascular biology 149 17761937
2017 Potential Role of ANGPTL4 in the Cross Talk between Metabolism and Cancer through PPAR Signaling Pathway. PPAR research 139 28182091
2020 Angiopoietin-like protein 8 differentially regulates ANGPTL3 and ANGPTL4 during postprandial partitioning of fatty acids. Journal of lipid research 134 32487544
2020 ANGPTL4: a multifunctional protein involved in metabolism and vascular homeostasis. Current opinion in hematology 129 32205586
2021 Role and mechanism of the action of angiopoietin-like protein ANGPTL4 in plasma lipid metabolism. Journal of lipid research 118 34801488
2002 Hypoxia up-regulates expression of peroxisome proliferator-activated receptor gamma angiopoietin-related gene (PGAR) in cardiomyocytes: role of hypoxia inducible factor 1alpha. Journal of molecular and cellular cardiology 118 12099716
2018 Absence of ANGPTL4 in adipose tissue improves glucose tolerance and attenuates atherogenesis. JCI insight 114 29563332
2009 Genetic variation in ANGPTL4 provides insights into protein processing and function. The Journal of biological chemistry 114 19270337
2013 Role of Angptl4 in vascular permeability and inflammation. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 107 24173241
2018 Brown adipose tissue derived ANGPTL4 controls glucose and lipid metabolism and regulates thermogenesis. Molecular metabolism 99 29627378
2010 Hypothalamic Angptl4/Fiaf is a novel regulator of food intake and body weight. Diabetes 99 20798332
2021 Hepatocyte-specific suppression of ANGPTL4 improves obesity-associated diabetes and mitigates atherosclerosis in mice. The Journal of clinical investigation 94 34255741
2019 Antiinflammatory activity of ANGPTL4 facilitates macrophage polarization to induce cardiac repair. JCI insight 91 31434807
2016 ANGPTL4 deficiency in haematopoietic cells promotes monocyte expansion and atherosclerosis progression. Nature communications 88 27460411
2011 Expression of angiopoietin-like 4 (ANGPTL4) in human colorectal cancer: ANGPTL4 promotes venous invasion and distant metastasis. Oncology reports 84 21308352
2012 Inverse PPARβ/δ agonists suppress oncogenic signaling to the ANGPTL4 gene and inhibit cancer cell invasion. Oncogene 77 23208498
2013 ANGPTL4 expression induced by butyrate and rosiglitazone in human intestinal epithelial cells utilizes independent pathways. American journal of physiology. Gastrointestinal and liver physiology 73 23518684
2020 Pharmacological aspects of ANGPTL3 and ANGPTL4 inhibitors: New therapeutic approaches for the treatment of atherogenic dyslipidemia. Pharmacological research 68 31931117
2020 Fasting induces ANGPTL4 and reduces LPL activity in human adipose tissue. Molecular metabolism 58 32504883
2023 Dual role of ANGPTL4 in inflammation. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 56 37300585
2020 Oleic acid-induced NOX4 is dependent on ANGPTL4 expression to promote human colorectal cancer metastasis. Theranostics 54 32641980
2018 Increased plasma and adipose tissue levels of ANGPTL8/Betatrophin and ANGPTL4 in people with hypertension. Lipids in health and disease 46 29490644
2007 Regulation of angiopoietin-like protein 4/fasting-induced adipose factor (Angptl4/FIAF) expression in mouse white adipose tissue and 3T3-L1 adipocytes. The British journal of nutrition 46 18081944
2017 The glucocorticoid-Angptl4-ceramide axis induces insulin resistance through PP2A and PKCζ. Science signaling 44 28743803
2017 The long non-coding RNA PVT1 represses ANGPTL4 transcription through binding with EZH2 in trophoblast cell. Journal of cellular and molecular medicine 44 29193797
2022 ANGPTL4 regulate glutamine metabolism and fatty acid oxidation in nonsmall cell lung cancer cells. Journal of cellular and molecular medicine 43 35285130
2018 Structures of Angptl3 and Angptl4, modulators of triglyceride levels and coronary artery disease. Scientific reports 43 29713054
2019 Characterization of ANGPTL4 function in macrophages and adipocytes using Angptl4-knockout and Angptl4-hypomorphic mice. Journal of lipid research 41 31409739
2017 Paeoniflorin ameliorates Adriamycin-induced nephrotic syndrome through the PPARγ/ANGPTL4 pathway in vivo and vitro. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 41 28972886
2016 ANGPTL4 Correlates with NSCLC Progression and Regulates Epithelial-Mesenchymal Transition via ERK Pathway. Lung 41 27166634
2021 G protein-coupled estrogen receptor stimulates human trophoblast cell invasion via YAP-mediated ANGPTL4 expression. Communications biology 39 34773076
2024 ANGPTL4 accelerates ovarian serous cystadenocarcinoma carcinogenesis and angiogenesis in the tumor microenvironment by activating the JAK2/STAT3 pathway and interacting with ESM1. Journal of translational medicine 37 38212795
2023 ANGPTL4 stabilizes atherosclerotic plaques and modulates the phenotypic transition of vascular smooth muscle cells through KLF4 downregulation. Experimental & molecular medicine 37 36782020
2021 Regulation of plasma triglyceride partitioning by adipose-derived ANGPTL4 in mice. Scientific reports 37 33846453
2012 Intronic cis-regulatory modules mediate tissue-specific and microbial control of angptl4/fiaf transcription. PLoS genetics 37 22479192
2023 Eucommia bark/leaf extract improves HFD-induced lipid metabolism disorders via targeting gut microbiota to activate the Fiaf-LPL gut-liver axis and SCFAs-GPR43 gut-fat axis. Phytomedicine : international journal of phytotherapy and phytopharmacology 36 36638713
2023 Cancer-associated mesothelial cell-derived ANGPTL4 and STC1 promote the early steps of ovarian cancer metastasis. JCI insight 36 36795484
2017 ANGPTL-4 induces diabetic retinal inflammation by activating Profilin-1. Experimental eye research 36 29031854
2020 Secreted Factors from Adipose Tissue Reprogram Tumor Lipid Metabolism and Induce Motility by Modulating PPARα/ANGPTL4 and FAK. Molecular cancer research : MCR 35 32859692
2021 The Pathogenic Role of Long Non-coding RNA H19 in Atherosclerosis via the miR-146a-5p/ANGPTL4 Pathway. Frontiers in cardiovascular medicine 33 34820432
2015 Angptl4 links α-cell proliferation following glucagon receptor inhibition with adipose tissue triglyceride metabolism. Proceedings of the National Academy of Sciences of the United States of America 31 26621734
2024 Renal Angptl4 is a key fibrogenic molecule in progressive diabetic kidney disease. Science advances 30 39630889
2020 ANGPTL4 exacerbates pancreatitis by augmenting acinar cell injury through upregulation of C5a. EMBO molecular medicine 30 32638512
2020 Decreased ANGPTL4 impairs endometrial angiogenesis during peri-implantation period in patients with recurrent implantation failure. Journal of cellular and molecular medicine 30 32745373
2021 GPIHBP1 and ANGPTL4 Utilize Protein Disorder to Orchestrate Order in Plasma Triglyceride Metabolism and Regulate Compartmentalization of LPL Activity. Frontiers in cell and developmental biology 29 34336854
2019 An ANGPTL4-ceramide-protein kinase Cζ axis mediates chronic glucocorticoid exposure-induced hepatic steatosis and hypertriglyceridemia in mice. The Journal of biological chemistry 29 31053639
2024 Adipose-derived stem cells promote glycolysis and peritoneal metastasis via TGF-β1/SMAD3/ANGPTL4 axis in colorectal cancer. Cellular and molecular life sciences : CMLS 28 38643448
2014 ANGPTL4 regulates the metastatic potential of oral squamous cell carcinoma. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 28 25060575
2025 Safety and efficacy of a novel ANGPTL4 inhibitory antibody for lipid lowering: results from phase 1 and phase 1b/2a clinical studies. Lancet (London, England) 27 40383129
2015 Regulation and clinical significance of the hypoxia-induced expression of ANGPTL4 in gastric cancer. Oncology letters 27 26893686
2024 Single-cell transcriptomic profiling of heart reveals ANGPTL4 linking fibroblasts and angiogenesis in heart failure with preserved ejection fraction. Journal of advanced research 25 38346487
2024 Cancer-associated fibroblasts regulate mitochondrial metabolism and inhibit chemosensitivity via ANGPTL4-IQGAP1 axis in prostate cancer. Journal of advanced research 24 39647634
2021 ANGPTL4 accelerates KRASG12D-Induced acinar to ductal metaplasia and pancreatic carcinogenesis. Cancer letters 24 34311032
2021 DNA methylation mediated down-regulation of ANGPTL4 promotes colorectal cancer metastasis by activating the ERK pathway. Journal of Cancer 24 34405010
2020 Calcineurin inhibitors ameliorate PAN-induced podocyte injury through the NFAT-Angptl4 pathway. The Journal of pathology 24 32686149
2021 Angiopoietin-like protein 4 (ANGPTL4) is an inhibitor of endothelial lipase (EL) while the ANGPTL4/8 complex has reduced EL-inhibitory activity. Heliyon 23 34504977
2020 Curcumin enhances chemotherapeutic effects and suppresses ANGPTL4 in anoikis-resistant cholangiocarcinoma cells. Heliyon 23 32051864
2014 Promising role of ANGPTL4 gene in diabetic wound healing. The international journal of lower extremity wounds 23 24659626
2022 Single-cell analysis of skin immune cells reveals an Angptl4-ifi20b axis that regulates monocyte differentiation during wound healing. Cell death & disease 22 35210411
2022 ANGPTL4 negatively regulates the progression of osteosarcoma by remodeling branched-chain amino acid metabolism. Cell death discovery 22 35461343
2021 ANGPTL4 regulates CD163 expression and Kuppfer cell polarization induced cirrhosis via TLR4/NF-κB pathway. Experimental cell research 22 34146541
2020 ANGPTL4 Promotes the Proliferation of Papillary Thyroid Cancer via AKT Pathway. OncoTargets and therapy 22 32231436
2016 The downregulation of ANGPTL4 inhibits the migration and proliferation of tongue squamous cell carcinoma. Archives of oral biology 22 27505034
2015 Lactobacillus rhamnosus CNCMI-4317 Modulates Fiaf/Angptl4 in Intestinal Epithelial Cells and Circulating Level in Mice. PloS one 22 26439630
2024 Associations of Circulating ANGPTL3, C-Terminal Domain-Containing ANGPTL4, and ANGPTL3/8 and ANGPTL4/8 Complexes with LPL Activity, Diabetes, Inflammation, and Cardiovascular Mortality. Circulation 21 39392008
2023 Inverse effects of APOC2 and ANGPTL4 on the conformational dynamics of lid-anchoring structures in lipoprotein lipase. Proceedings of the National Academy of Sciences of the United States of America 21 37094117
2022 Genetic Mimicry Analysis Reveals the Specific Lipases Targeted by the ANGPTL3-ANGPTL8 Complex and ANGPTL4. Journal of lipid research 21 36372100
2021 Research Progress on the Involvement of ANGPTL4 and Loss-of-Function Variants in Lipid Metabolism and Coronary Heart Disease: Is the "Prime Time" of ANGPTL4-Targeted Therapy for Coronary Heart Disease Approaching? Cardiovascular drugs and therapy 21 32500296
2023 ANGPTL4 suppresses the profibrogenic functions of atrial fibroblasts induced by angiotensin II by up-regulating PPARγ. Iranian journal of basic medical sciences 20 37051105
2022 ANGPTL4 attenuates palmitic acid-induced endothelial cell injury by increasing autophagy. Cellular signalling 20 35843572
2022 ANGPTL4 Regulates Psoriasis via Modulating Hyperproliferation and Inflammation of Keratinocytes. Frontiers in pharmacology 20 35860030
2018 Role of Angptl4/Fiaf in exercise-induced skeletal muscle AMPK activation. Journal of applied physiology (Bethesda, Md. : 1985) 20 29952246
2017 Angptl4 does not control hyperglucagonemia or α-cell hyperplasia following glucagon receptor inhibition. Proceedings of the National Academy of Sciences of the United States of America 20 28143927
2022 ANGPTL4 Regulates Lung Adenocarcinoma Pyroptosis and Apoptosis via NLRP3\ASC\Caspase 8 Signaling Pathway to Promote Resistance to Gefitinib. Journal of oncology 19 36467503
2020 MNK1 signaling induces an ANGPTL4-mediated gene signature to drive melanoma progression. Oncogene 19 32132651
2024 The ANGPTL4-HIF-1α loop: a critical regulator of renal interstitial fibrosis. Journal of translational medicine 18 38992710
2022 Silencing of Angiopoietin-Like Protein 4 (Angptl4) Decreases Inflammation, Extracellular Matrix Degradation, and Apoptosis in Osteoarthritis via the Sirtuin 1/NF-κB Pathway. Oxidative medicine and cellular longevity 18 36071864
2021 Nickel chloride regulates ANGPTL4 via the HIF-1α-mediated TET1 expression in lung cells. Toxicology letters 18 34571076
2019 PRSS21/testisin inhibits ovarian tumor metastasis and antagonizes proangiogenic angiopoietins ANG2 and ANGPTL4. Journal of molecular medicine (Berlin, Germany) 18 30911775
2024 SGLT2 inhibitor downregulates ANGPTL4 to mitigate pathological aging of cardiomyocytes induced by type 2 diabetes. Cardiovascular diabetology 17 39633372
2024 FGF19-Activated Hepatic Stellate Cells Release ANGPTL4 that Promotes Colorectal Cancer Liver Metastasis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 17 39716892
2022 ANGPTL4: a new mode in the regulation of intravascular lipolysis. Current opinion in lipidology 17 34860701
2017 ANGPTL4 T266M variant is associated with reduced cancer invasiveness. Biochimica et biophysica acta. Molecular cell research 17 28641978
2013 Upregulation of ANGPTL4 messenger RNA and protein in severely calcified carotid plaques. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 17 24075588
2023 ANGPTL4 inhibits granulosa cell proliferation in polycystic ovary syndrome by EGFR/JAK1/STAT3-mediated induction of p21. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16 36607250
2021 ANGPTL4 Attenuates Ang II-Induced Atrial Fibrillation and Fibrosis in Mice via PPAR Pathway. Cardiology research and practice 16 34422410
2020 EZH2 inhibition promotes ANGPTL4/CREB1 to suppress the progression of ulcerative colitis. Life sciences 16 32194081
2020 Danlou Tablet Improves Chronic Intermittent Hypoxia-Induced Dyslipidemia and Arteriosclerosis by HIF-1α-Angptl4 mRNA Signaling Pathway. Chinese journal of integrative medicine 16 32623702
2019 PPARβ/δ recruits NCOR and regulates transcription reinitiation of ANGPTL4. Nucleic acids research 16 31428774
2018 ANGPTL4 gene E40K variation protects against obesity-associated dyslipidemia in participants with obesity. Obesity science & practice 16 30820332
2023 STAT2-induced linc02231 promotes tumorigenesis and angiogenesis through modulation of hnRNPA1/ANGPTL4 in colorectal cancer. The journal of gene medicine 15 36994700
2023 HIF-1α regulates osteoclastogenesis and alveolar bone resorption in periodontitis via ANGPTL4. Archives of oral biology 15 37290266
2014 Differential expression and effect of the porcine ANGPTL4 gene on intramuscular fat. Genetics and molecular research : GMR 15 24782129
2025 COL1A1-positive endothelial cells promote gastric cancer progression via the ANGPTL4-SDC4 axis driven by endothelial-to-mesenchymal transition. Cancer letters 14 40254092

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