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Showing FABP4 — AP2 is a alias.

FABP4

Fatty acid-binding protein, adipocyte · UniProt P15090

Length
132 aa
Mass
14.7 kDa
Annotated
2026-06-09
100 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FABP4 is a fatty acid-binding protein that functions both as an intracellular lipid chaperone and as a secreted hormone coordinating lipid metabolism, inflammation, and systemic glucose homeostasis (PMID:34880500, PMID:37279064). As a circulating hormone, FABP4 is released from adipocytes upon lipolytic stimulation and constitutively from endothelial cells, which supply the majority of basal plasma FABP4 and are required for the lipolysis-driven insulin secretion response (PMID:37279064); its secretion proceeds through an unconventional ER-Golgi-independent route involving endosomes and secretory lysosomes (PMID:29212659). Once extracellular, FABP4 assembles with adenosine kinase and nucleoside diphosphate kinase into the 'Fabkin' complex that regulates extracellular ATP/ADP levels and modulates beta-cell function, and antibody targeting of this complex improves metabolic outcomes in diabetes models (PMID:34880500); it also engages cytokeratin 1 on the endothelial surface to drive NRF2 oxidative-stress and NF-κB inflammatory signaling (PMID:30521939). Intracellularly, FABP4 binds fatty acids in distinct dynamic states (PMID:38777142) and shapes nuclear-receptor signaling: it triggers ubiquitin-proteasomal degradation of PPARγ to restrain adipogenesis (PMID:24319114), yet supports fatty acid-induced PPARγ activation and lipid signaling in polarized macrophages (PMID:25897794, PMID:31926616). Its lipolytic role is gated by PAK4, which phosphorylates FABP4 at T126 to impair the FABP4–HSL interaction and suppress lipolysis (PMID:38216738). In brown adipocytes FABP4 promotes adaptive thermogenesis by inhibiting LXRα to induce DIO2-mediated T4-to-T3 conversion (PMID:28128199), and in macrophages it controls a UCP2-dependent redox circuit that governs NLRP3 inflammasome activation and IL-1β output (PMID:27795298). Across diverse immune and stromal contexts FABP4 acts as a pro-inflammatory node, driving NF-κB-dependent chemokine production and macrophage recruitment in tissue and tumor microenvironments (PMID:37487374, PMID:33931964, PMID:39513934).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2013 High

    Established that beyond lipid binding FABP4 actively regulates the master adipogenic transcription factor PPARγ, explaining how it restrains fat-cell formation.

    Evidence Ubiquitination and proteasome-inhibition assays with FABP4-null preadipocyte/macrophage complementation rescue

    PMID:24319114

    Open questions at the time
    • Does not define the E3 ligase or direct biochemical mechanism of PPARγ ubiquitination
    • Reconciliation with FABP4 supporting PPARγ activation in macrophages unresolved
  2. 2017 High

    Showed FABP4 drives adaptive thermogenesis through an LXRα→DIO2 axis, linking the chaperone to thyroid hormone activation in brown fat.

    Evidence A-FABP knockout mice with cold/HFD challenge and recombinant protein rescue, LXRα inhibition assays

    PMID:28128199

    Open questions at the time
    • Mechanism by which FABP4 inhibits LXRα not defined
    • Direct vs indirect effect on DIO2 transcription unclear
  3. 2017 High

    Defined the unconventional secretory route for FABP4, resolving how a cytosolic protein reaches the circulation.

    Evidence Subcellular fractionation, exclusion of ER-Golgi/GRASP/autophagy/MVB routes, chloroquine inhibition in vivo

    PMID:29212659

    Open questions at the time
    • Molecular machinery sorting FABP4 into endosomes/secretory lysosomes unknown
    • Signal triggering release not identified
  4. 2017 High

    Connected FABP4 to a UCP2-dependent redox circuit controlling NLRP3 inflammasome activity, a mechanism for its pro-inflammatory action in macrophages.

    Evidence FABP4-null macrophages with UCP2 siRNA rescue, ROS/protein-oxidation and caspase-1/IL-1β readouts, chemical inhibitor

    PMID:27795298

    Open questions at the time
    • How FABP4 represses UCP2 mechanistically not established
    • Link between lipid binding and mitochondrial redox not biochemically resolved
  5. 2021 High

    Identified FABP4 as a secreted hormone forming the Fabkin complex that regulates extracellular nucleotides and beta-cell function, a paradigm-shifting extracellular role.

    Evidence Complex identification, T1D/T2D mouse models, antibody-mediated targeting, extracellular ATP/ADP measurement

    PMID:34880500

    Open questions at the time
    • Structural basis of the Fabkin assembly not resolved
    • Receptor/sensing mechanism on beta-cells unclear
  6. 2018 Medium

    Demonstrated a direct extracellular receptor for FABP4 (cytokeratin 1) on endothelial cells, defining how circulating FABP4 transmits oxidative/inflammatory signals.

    Evidence Surface plasmon resonance binding, CK1 siRNA knockdown in HUVECs, NRF2/p65 readouts

    PMID:30521939

    Open questions at the time
    • Single lab, no in vivo CK1 genetic validation
    • Downstream signal transduction from CK1 not defined
  7. 2023 High

    Quantified the cellular origins of circulating FABP4, showing endothelium supplies basal hormone and adipocytes the lipolytic surge, refining the source of the metabolic hormone.

    Evidence Four cell-type-specific Fabp4 knockout lines, plasma FABP4 quantification, lipolysis and insulin secretion assays

    PMID:37279064

    Open questions at the time
    • Mechanism of constitutive endothelial secretion not defined
    • How endothelial FABP4 couples to islet insulin secretion unresolved
  8. 2024 High

    Placed FABP4 under kinase control by PAK4, identifying a phosphosite that gates the FABP4–HSL interaction and lipolysis within the cAMP-PKA axis.

    Evidence In vitro kinase assay with phosphosite mapping (T126), adipose-specific PAK4 OE/KO mice, FABP4–HSL co-IP

    PMID:38216738

    Open questions at the time
    • Structural effect of T126 phosphorylation on FABP4 not resolved
    • Whether phospho-FABP4 alters lipid binding unknown
  9. 2024 Medium

    Characterized the biophysics of FABP4 ligand binding, revealing temperature-dependent intermediate and strongly bound fatty acid states.

    Evidence Microscale thermophoresis and CW EPR with spin-labeled stearic acid

    PMID:38777142

    Open questions at the time
    • No mutagenesis linking binding states to function
    • Cellular relevance of the two states untested
  10. 2024 Medium

    Extended FABP4's pro-inflammatory function across tissues, showing NF-κB-driven chemokine programs in endothelium, macrophages, T cells, and stroma promote recruitment and disease in metabolic, autoimmune, and tumor settings.

    Evidence Cell-type-specific KO and inhibitor studies across NAFLD, NOD diabetes, cancer co-culture and metastasis models with CXCL10/CXCL1/IL-1 readouts

    PMID:30462529 PMID:37487374 PMID:37741433 PMID:38884133 PMID:39513934

    Open questions at the time
    • Whether these effects depend on intracellular lipid chaperoning or extracellular signaling not always distinguished
    • Most contexts validated in single labs

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single fatty acid-binding protein reconciles opposing roles (PPARγ degradation vs activation; intracellular chaperone vs extracellular hormone) and the structural/receptor basis of its extracellular signaling remain open.
  • No unifying structural model linking ligand state, phosphorylation, and partner choice
  • Extracellular receptor repertoire beyond CK1 unresolved
  • Mechanism switching FABP4 between pro- and anti-adipogenic outputs unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 2 GO:0048018 receptor ligand activity 2
Localization
GO:0005576 extracellular region 2 GO:0005829 cytosol 2 GO:0005764 lysosome 1 GO:0005768 endosome 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-9609507 Protein localization 1
Partners
ADKCD36HSLKRT1NDPKPAK4PPARGSIRT5
Complex memberships
Fabkin (FABP4-ADK-NDPK)

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 Hormonal FABP4 forms a functional hormone complex with adenosine kinase (ADK) and nucleoside diphosphate kinase (NDPK), designated 'Fabkin', to regulate extracellular ATP and ADP levels and thereby modulate beta-cell function; antibody-mediated targeting of this complex improved metabolic outcomes and preserved beta-cell integrity in mouse models of both type 1 and type 2 diabetes. Complex identification, in vivo mouse models (T1D and T2D), antibody-mediated targeting, measurement of extracellular ATP/ADP levels Nature High 34880500
2013 FABP4 triggers ubiquitination and subsequent proteasomal degradation of PPARγ in adipocytes and macrophages, thereby downregulating adipogenesis; FABP4-null preadipocytes exhibit markedly enhanced adipogenesis that is reversed by FABP4 complementation. Ubiquitination assay, proteasome inhibition, FABP4-null mouse preadipocytes and macrophages, complementation rescue experiment Diabetes High 24319114
2017 FABP4 (A-FABP) promotes adaptive thermogenesis by inducing type-II iodothyronine deiodinase (DIO2) expression in brown adipocytes via inhibition of liver X receptor α (LXRα), leading to conversion of inactive T4 to active T3; A-FABP knockout mice have reduced thermogenesis reversible by recombinant A-FABP infusion. A-FABP knockout mice, cold stress and high-fat diet challenges, recombinant protein infusion rescue, gene expression analysis, LXRα inhibition assays Nature communications High 28128199
2017 FABP4 secretion from adipocytes occurs via an unconventional pathway involving enclosure within endosomes and secretory lysosomes, independent of the ER-Golgi pathway, GRASP proteins, autophagy, and multivesicular bodies; chloroquine treatment inhibits plasma FABP4 elevation in mice. Subcellular fractionation, membrane-bounded compartment tracing, pharmacological inhibition (chloroquine) in mice, exclusion of alternative secretory routes The Journal of cell biology High 29212659
2023 Endothelial cells are the major source of baseline circulating (hormonal) FABP4, contributing ~87% of basal plasma FABP4; adipocytes are the main source of the lipolysis-stimulated rise in plasma FABP4 (~62% of induction); myeloid cells do not contribute detectably to circulating FABP4. Endothelial-derived FABP4 is required for the insulin secretion response to lipolysis. Cell-type-specific Fabp4 knockout mice (adipocyte, endothelial, myeloid, total), plasma FABP4 measurement, lipolysis stimulation, insulin secretion assay JCI insight High 37279064
2024 PAK4 directly phosphorylates FABP4 at T126 and HSL at S565, impairing the FABP4–HSL interaction and inhibiting lipolysis; adipose-specific PAK4 overexpression attenuates lipolysis and exacerbates obesity, whereas PAK4 knockout or inhibition enhances lipolysis and ameliorates diet-induced obesity and insulin resistance. PKA targets PAK4 for degradation, placing PAK4 as a counter-regulatory node in the cAMP-PKA lipolysis pathway. In vitro kinase assay with phosphosite identification, adipose-specific PAK4 overexpression and KO mice, co-IP of FABP4–HSL, high-fat diet metabolic phenotyping, PAK4 inhibitor treatment Nature metabolism High 38216738
2017 Ablation of FABP4/aP2 in macrophages upregulates UCP2, reduces mitochondrial protein oxidation and the mitochondrial unfolded-protein response, and attenuates NLRP3 inflammasome activation and IL-1β secretion; these effects are partially reversed by UCP2 silencing in FABP4-null macrophages, establishing a FABP4→UCP2→redox→NLRP3 pathway. FABP4-null macrophages, UCP2 siRNA rescue, ROS/protein oxidation assays, NLRP3 inflammasome activation (caspase-1 cleavage, IL-1β secretion), chemical FABP4 inhibitor Molecular and cellular biology High 27795298
2018 Macrophage-derived FABP4 is required for CXCL1 production by alveolar macrophages and subsequent neutrophil recruitment in Pseudomonas aeruginosa pneumonia; bone marrow chimera experiments confirmed macrophages as the protective FABP4 source, and recombinant CXCL1 delivery rescued FABP4-null mice from increased mortality. FABP4-knockout mice, bone marrow chimera reconstitution, intratracheal P. aeruginosa challenge, recombinant CXCL1 rescue, CXCL1 ELISA from alveolar macrophages FASEB journal High 30462529
2022 SIRT5 physically interacts with FABP4 (Co-IP) and promotes FABP4 deacetylation, reducing FABP4 expression and thereby promoting non-small cell lung cancer progression; silencing SIRT5 increases FABP4 acetylation and expression, reducing cancer cell malignancy. Co-immunoprecipitation, western blot for acetylation, shRNA knockdown of SIRT5 and FABP4 in NSCLC cells, in vivo xenograft Neoplasma Medium 35603953
2018 FABP4 interacts with cytokeratin 1 (CK1) on the endothelial cell surface (demonstrated by surface plasmon resonance); CK1-mediated FABP4 uptake regulates endothelial oxidative stress (NRF2) and inflammation (NF-κB/p65) responses, and CK1 knockdown blocks eFABP4 pro-inflammatory and pro-oxidative effects. Surface plasmon resonance (direct binding), siRNA knockdown of CK1 in HUVECs, western blotting for NRF2 and p65 nuclear translocation, palmitate co-treatment Biochimica et biophysica acta. Molecular and cell biology of lipids Medium 30521939
2021 CD36 directly interacts with FABP4 to regulate fatty acid import, transport, and metabolism in breast cancer cells co-cultured with adipocytes; CD36 activates STAT3 signalling with a feedforward loop (STAT3 binds CD36 promoter), and combined CD36/FABP4 inhibition induces apoptosis. Co-culture experiments, genetic ablation of CD36, Co-IP of CD36–FABP4 interaction, ChIP/reporter for STAT3-CD36 promoter binding, apoptosis assays NPJ breast cancer Medium 34561446
2021 FABP4 in tumor-associated macrophages directly binds to ATP synthase β subunit (ATPB) and promotes its ubiquitination, leading to decreased intracellular ATP and deactivation of the NF-κB/RelA–IL-1α pathway, reprogramming macrophages to an anti-inflammatory phenotype that promotes neuroblastoma progression. Co-IP of FABP4–ATPB, ubiquitination assay, ATP measurement, NF-κB pathway analysis, IL-1α blocking antibody rescue, in vitro and in vivo tumor progression assays Clinical and translational medicine Medium 33931964
2021 FABP4 activates the JAK2/STAT2 signaling pathway in homocysteine-induced macrophage inflammation via Rap1a-mediated Tyr416 phosphorylation and membrane translocation of c-Src; SOCS1 provides negative feedback inhibition of this pathway and reduces Rap1a expression. Western blot for JAK2/STAT2 and c-Src phosphorylation, Rap1a manipulation, pharmacological inhibition in ApoE-/- mice, pathway inhibitor studies Laboratory investigation Medium 34725437
2024 FABP4 activates the AMPK/JAK/STAT axis in a novel FABP4+C1q+ macrophage subtype, promoting fatty acid synthesis, anti-apoptosis, and phagocytic ability; FABP4 and C1q synergistically regulate proinflammatory cytokine expression in these macrophages. Single-cell RNA sequencing, multiplex fluorescent immunohistochemistry, mechanistic pathway (AMPK/JAK/STAT) analysis, functional phagocytosis/apoptosis assays Cell death & disease Low 39353883
2023 FABP4 in liver sinusoidal endothelial cells (LSECs) promotes CXCL10 expression via NF-κB/p65 signaling, driving CXCR3+ macrophage recruitment and M1 macrophage polarization during NAFLD progression; FABP4 inhibition reduces CXCL10 and M1 polarization. FABP4 inhibition in HFD mice, flow cytometry for macrophage subtypes, co-culture of TMNK-1 cells with macrophages, NF-κB inhibitor, recombinant CXCL10 treatment Biochimica et biophysica acta. Molecular basis of disease Medium 37487374
2019 FABP4 supports fatty acid-induced PPARγ activation in IL-4-polarized macrophages, leading to upregulation of lipoprotein lipase (LPL), VLDL-induced triglyceride accumulation (foam cell formation), and CCL2/IL-1β inflammatory mediator expression; FABP4 inhibition (chemical or siRNA) reduces all these effects. FABP4 siRNA knockdown, chemical inhibitors (BMS309403, HTS01037), PPARγ luciferase reporter assay, lipid accumulation assay in primary human macrophages Atherosclerosis Medium 25897794
2019 Exogenous FABP4 activates p38 MAPK, which mediates both HSL (Ser-660) phosphorylation-dependent lipolysis and NF-κB-mediated inflammation in adipocytes; these effects are blocked by the p38 inhibitor SB203580 and FABP4 inhibitor I-9 in vitro and in vivo. Recombinant FABP4 treatment of 3T3-L1 cells and C57BL/6J mice, western blot for p38, HSL-pSer660, NF-κB, p38 and FABP4 inhibitor intervention Endocrine Medium 31845180
2022 Microglial FABP4 deficiency prevents high-fat diet-induced cognitive decline in mice, associated with reduced hippocampal neuroinflammation (inflammatory cytokines and microgliosis) and increased microglial UCP2 expression, defining a microglial FABP4–UCP2 axis in diet-induced neuroinflammation. Microglial-specific FABP4 knockout (AKO) mice, HFD challenge, behavioral testing (T-maze, Barnes maze), hippocampal cytokine panel, UCP2 RT-PCR, IHC for microgliosis International journal of molecular sciences Medium 35457171
2018 FABP4 expression in eosinophils is induced by TNF-α, IL-4, and IL-13; FABP4-deficient eosinophils show decreased spreading, adhesion (reduced β2-integrin), migration, F-actin polymerization, calcium flux, and ERK1/2 phosphorylation in response to eotaxin-1; in vivo, FABP4-null mice exhibit attenuated eosinophilia and airway inflammation in a cockroach antigen model. FABP4-knockout mice, allergen challenge model, eosinophil adhesion and migration assays, calcium flux measurement, ERK1/2 western blot, F-actin polymerization assay American journal of physiology. Lung cellular and molecular physiology Medium 29696987
2024 FABP4 directly activates NF-κB signaling in chondrocytes (validated in ATDC5 cells and FABP4-KO vs WT mice), leading to upregulation of catabolic markers; dual FABP4 and NF-κB inhibition alleviates OA in high-fat diet mice, whereas FABP4 had no significant effect on JNK signaling in this context. FABP4-KO mice, NF-κB-specific inhibitor (QNZ) and siRNA, FABP4 inhibitor (BMS309403), ATDC5 chondrocyte culture with recombinant FABP4, HFD OA model FASEB journal Medium 38095503
2024 FABP4 inhibition (BMS309403) suppresses osteoclast differentiation by modulating calcium signaling and inhibiting the Ca2+-Calcineurin-NFATc1 pathway, without affecting osteoblast differentiation, and increases bone mineral density in ovariectomized mice. Osteoclast/osteoblast differentiation assays, Ca2+ signaling and NFATc1 pathway analysis, ovariectomized mouse model with BMS309403 treatment, bone mineral density measurement Nature communications Medium 40360512
2024 FABP4 activates the FABP4/CEBPα pathway in macrophages in response to unsaturated fatty acids (particularly linoleic acid), leading to triglyceride synthesis and lipid droplet formation; FABP4 also enhances lipolysis and FA utilization by breast cancer cells, promoting metastasis in vitro and in vivo; FABP4 deficiency in macrophages significantly reduces linoleic acid-induced lipid metabolism. Murine macrophage lipid droplet formation assays, FABP4-deficient macrophages, CEBPα pathway analysis, co-culture with breast cancer cell lines, migration assays, in vivo metastasis model eLife Medium 39513934
2021 FABP4 in macrophages activates the NLRP3/IL-1β axis by facilitating transfer of saturated fatty acids to induce caspase-1/GSDMD-dependent pyroptosis, which then promotes EMT signaling in pancreatic cancer cells to drive metastasis. In vivo and in vitro experiments with FABP4-overexpressing macrophages, caspase-1/GSDMD pathway analysis, NLRP3 inhibition, co-culture of macrophages with PC cells, EMT marker assessment Cancer letters Medium 37741433
2024 FABP4 facilitates EMT in glioblastoma cells by upregulating CD36 expression, which promotes EMT via non-canonical TGFβ pathways; FABP4 overexpression increases filopodia formation and invasion, and loss-of-function reduces these effects in vitro and in an intracranial model. Gain- and loss-of-function experiments, DEG and GSEA analysis, CD36 expression assays, non-canonical TGFβ pathway western blot, intracranial glioma mouse model Neoplasia Medium 39243502
2019 Nitro-fatty acids (NO2-FA) bind directly to FABP4 (demonstrated in vitro and in silico), and FABP4 facilitates NO2-FA-induced PPARγ, Keap1/Nrf2, and HSF1 signaling in monocytes; FABP4 inhibition attenuates these downstream signaling actions, establishing a FABP4-PPARγ positive amplification loop for NO2-FA signaling. In vitro fatty acid binding assay, molecular docking (in silico), FABP4 inhibitor treatment, PPARγ reporter gene assays in primary human monocytes/macrophages Redox biology Medium 31926616
2024 FABP4 promotes survival and alarming function of islet-resident memory T cells (TRM) by promoting fatty acid utilization and CXCL10 secretion; genetic deletion of FABP4 in NOD mice reduced cytotoxic T cell recruitment, delayed T1D incidence, and suppressed CXCL10 production. NOD mouse FABP4 genetic deletion, CD69 neutralizing antibody depletion of TRM cells, flow cytometry for T cell populations, CXCL10 measurement, diabetes incidence tracking Advanced science Medium 38884133
2023 FABP4 controls fat mass homeostasis (adipocyte size and number) through a negative feedback loop: fatty acid-mediated FAT/CD36-PPARγ signaling induces FABP4 expression, and accumulated intracellular FABP4 in turn inhibits CD36 signaling in both adipocytes and progenitors. Real-time proliferation/differentiation/lipolysis assays in 3T3-L1, 3T3-MBX, and human adipose stem cells; co-culture; FABP4 uptake and CD36 signaling measurements International journal of molecular sciences Low 36674544
2021 FABP4 expressed in Paneth cells is regulated by gut Lactobacillus via TRAF2/TRAF6 ubiquitination-mediated NF-κB signaling; germ-free mice have reduced intestinal FABP4, restored by fecal transplantation or specific Lactobacillus colonization. Germ-free mice, fecal transplantation, Lactobacillus colonization, TRAF2/TRAF6 ubiquitination and NF-κB pathway analysis, Paneth cell-specific FABP4 expression assessment Scientific reports Low 26687459
2024 Fatty acid binding to FABP4 occurs in two distinct states ('intermediately' and 'strongly' bound) as revealed by CW EPR spectroscopy using spin-labeled stearic acid; binding proportions are strongly temperature- and concentration-dependent with the more dynamic 'intermediately bound' state dominating at body temperature. Microscale thermophoresis (MST), continuous-wave electron paramagnetic resonance (CW EPR) spectroscopy with spin-probe ligands, dynamic light scattering, bioinformatic analysis The Journal of biological chemistry Medium 38777142
2023 Kindlin-2 stabilizes fatty acid synthase (FAS) and promotes PPARγ activation and downstream FABP4 expression in adipocytes; increased FABP4 inhibits insulin expression and decreases bone mass; Kindlin-2 deletion reduces FABP4 and increases bone mass, reversible by PPARγ activation (rosiglitazone), establishing a Kindlin-2/FAS/PPARγ/FABP4/insulin axis. Adipocyte-specific Kindlin-2 KO mice, AAV-targeted knockdown, FAS inhibitor (C75), rosiglitazone rescue, FAS protein stability assay, PPARγ activation assay, bone density measurement Acta pharmaceutica Sinica. B Medium 37969743
2021 PXR mediates FABP4 expression in response to valproate in HepG2 cells; PXR knockdown reduces both FABP4 induction and lipid accumulation, while PXR overexpression enhances both; exogenous FABP4 overexpression independently increases triglyceride levels. PXR siRNA knockdown, PXR overexpression, FABP4 overexpression, triglyceride measurement, lipid accumulation assay in HepG2 cells Toxicology letters Low 33901630
2022 mTORC1 activity (controlled by TSC1 deletion or Rheb1 disruption in myeloid cells) regulates FABP4 expression in macrophages; mTORC1 activation increases FABP4 secretion from M1-polarized macrophages, promoting synovitis, angiogenesis, and cartilage degradation in RA; anagliptin (DPP4 inhibitor) and BMS309403 (FABP4 inhibitor) reduce FABP4 in synovial macrophages and alleviate RA. Myeloid-specific TSC1-deletion and Rheb1-disruption mice, BMS309403 and anagliptin treatment, in vivo RA mouse model, synovitis/angiogenesis/cartilage assays Bone research Medium 35729106
2024 FABP4 induces fibrosis, lipid accumulation, and altered glucose metabolism in epicardial stroma and atrial fibroblasts, and modifies lipid content and calcium dynamics in atrial cardiomyocytes, without affecting INa; these effects were demonstrated by direct FABP4 protein treatment of primary cell cultures. Primary epicardial/subcutaneous stroma and atrial fibroblast cultures, iPSC-derived and adult mouse atrial cardiomyocytes, FABP4 (100 ng/mL) treatment, proteomics, Raman microspectroscopy, calcium imaging, patch clamp Circulation. Arrhythmia and electrophysiology Medium 39212041

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Fatty Acid-Binding Protein 4 (FABP4): Pathophysiological Insights and Potent Clinical Biomarker of Metabolic and Cardiovascular Diseases. Clinical Medicine Insights. Cardiology 374 25674026
2013 FABP4 attenuates PPARγ and adipogenesis and is inversely correlated with PPARγ in adipose tissues. Diabetes 272 24319114
2020 Adipocyte-Induced FABP4 Expression in Ovarian Cancer Cells Promotes Metastasis and Mediates Carboplatin Resistance. Cancer research 234 32054768
2021 Tumor resistance to ferroptosis driven by Stearoyl-CoA Desaturase-1 (SCD1) in cancer cells and Fatty Acid Biding Protein-4 (FABP4) in tumor microenvironment promote tumor recurrence. Redox biology 231 34030117
2018 FABP4 as a key determinant of metastatic potential of ovarian cancer. Nature communications 181 30050129
2019 Adipokine FABP4 integrates energy stores and counterregulatory metabolic responses. Journal of lipid research 158 30705117
2021 Interaction between CD36 and FABP4 modulates adipocyte-induced fatty acid import and metabolism in breast cancer. NPJ breast cancer 130 34561446
2022 FABP4 secreted by M1-polarized macrophages promotes synovitis and angiogenesis to exacerbate rheumatoid arthritis. Bone research 97 35729106
2020 FABP4 promotes invasion and metastasis of colon cancer by regulating fatty acid transport. Cancer cell international 92 33088219
2017 A-FABP mediates adaptive thermogenesis by promoting intracellular activation of thyroid hormones in brown adipocytes. Nature communications 81 28128199
2017 Adipocyte fatty acid binding protein 4 (FABP4) inhibitors. A comprehensive systematic review. European journal of medicinal chemistry 81 28738306
2021 A hormone complex of FABP4 and nucleoside kinases regulates islet function. Nature 80 34880500
2017 FABP4/aP2 Regulates Macrophage Redox Signaling and Inflammasome Activation via Control of UCP2. Molecular and cellular biology 79 27795298
2017 Unconventional secretion of FABP4 by endosomes and secretory lysosomes. The Journal of cell biology 78 29212659
2021 Targeted Inhibition of LPL/FABP4/CPT1 fatty acid metabolic axis can effectively prevent the progression of nonalcoholic steatohepatitis to liver cancer. International journal of biological sciences 71 34803493
2012 FABP4 dynamics in obesity: discrepancies in adipose tissue and liver expression regarding circulating plasma levels. PloS one 69 23139800
2004 Atorvastatin reduces CD68, FABP4, and HBP expression in oxLDL-treated human macrophages. Biochemical and biophysical research communications 68 15110783
2020 FABP4: A New Player in Obesity-Associated Breast Cancer. Trends in molecular medicine 67 32359475
2016 Antiangiogenic and tumour inhibitory effects of downregulating tumour endothelial FABP4. Oncogene 65 27568980
2023 FABP4 in macrophages facilitates obesity-associated pancreatic cancer progression via the NLRP3/IL-1β axis. Cancer letters 57 37741433
2019 High expression of FABP4 and FABP6 in patients with colorectal cancer. World journal of surgical oncology 55 31651326
2019 Exogenous FABP4 interferes with differentiation, promotes lipolysis and inflammation in adipocytes. Endocrine 52 31845180
2019 FABP4 contributes to renal interstitial fibrosis via mediating inflammation and lipid metabolism. Cell death & disease 48 31097687
2022 Therapeutic Implications of FABP4 in Cancer: An Emerging Target to Tackle Cancer. Frontiers in pharmacology 47 35899119
2019 A FABP4-PPARγ signaling axis regulates human monocyte responses to electrophilic fatty acid nitroalkenes. Redox biology 47 31926616
2015 FABP4 inhibition suppresses PPARγ activity and VLDL-induced foam cell formation in IL-4-polarized human macrophages. Atherosclerosis 46 25897794
2022 Adipocyte fatty acid binding protein 4 (FABP4) inhibitors. An update from 2017 to early 2022. European journal of medicinal chemistry 44 35849941
2021 High expression of FABP4 in colorectal cancer and its clinical significance. Journal of Zhejiang University. Science. B 40 33615754
2023 Targeting FABP4 in elderly mice rejuvenates liver metabolism and ameliorates aging-associated metabolic disorders. Metabolism: clinical and experimental 39 36842611
2021 A-FABP in Metabolic Diseases and the Therapeutic Implications: An Update. International journal of molecular sciences 39 34502295
2021 FABP4 deactivates NF-κB-IL1α pathway by ubiquitinating ATPB in tumor-associated macrophages and promotes neuroblastoma progression. Clinical and translational medicine 38 33931964
2021 FABP4 activates the JAK2/STAT2 pathway via Rap1a in the homocysteine-induced macrophage inflammatory response in ApoE-/- mice atherosclerosis. Laboratory investigation; a journal of technical methods and pathology 38 34725437
2018 FABP4 regulates eosinophil recruitment and activation in allergic airway inflammation. American journal of physiology. Lung cellular and molecular physiology 36 29696987
2018 Macrophage FABP4 is required for neutrophil recruitment and bacterial clearance in Pseudomonas aeruginosa pneumonia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 36 30462529
2010 Associations of A-FABP and H-FABP markers with the content of intramuscular fat in Beijing-You chicken. Animal biotechnology 36 20024783
2021 Elevated circulating FABP4 concentration predicts cardiovascular death in a general population: a 12-year prospective study. Scientific reports 35 33597568
2023 FABP4 Controls Fat Mass Expandability (Adipocyte Size and Number) through Inhibition of CD36/SR-B2 Signalling. International journal of molecular sciences 33 36674544
2014 fabp4 is central to eight obesity associated genes: a functional gene network-based polymorphic study. Journal of theoretical biology 33 25280936
2018 FABP4 as a biomarker for knee osteoarthritis. Biomarkers in medicine 32 29393670
2024 Oleic acid-PPARγ-FABP4 loop fuels cholangiocarcinoma colonization in lymph node metastases microenvironment. Hepatology (Baltimore, Md.) 31 38377465
2024 FABP4-mediated lipid metabolism promotes TNBC progression and breast cancer stem cell activity. Cancer letters 31 39306229
2023 FABP4 in LSECs promotes CXCL10-mediated macrophage recruitment and M1 polarization during NAFLD progression. Biochimica et biophysica acta. Molecular basis of disease 31 37487374
2013 Increased leptin and A-FABP levels in relapsing and progressive forms of MS. BMC neurology 31 24215402
2020 Role of Fatty Acid Binding Protein 4 (FABP4) in Kidney Disease. Current medicinal chemistry 29 30306857
2016 Transcriptome and Metabolome Analyses in Exogenous FABP4- and FABP5-Treated Adipose-Derived Stem Cells. PloS one 29 27936164
2006 Unexpected high polymorphism at the FABP4 gene unveils a complex history for pig populations. Genetics 29 17057239
2023 Oridonin attenuates atherosclerosis by inhibiting foam macrophage formation and inflammation through FABP4/PPARγ signalling. Journal of cellular and molecular medicine 27 37905351
2014 Circulating FABP4 is a marker of metabolic and cardiovascular risk in SLE patients. Lupus 27 24390652
2008 A-FABP--a biomarker associated with the metabolic syndrome and/or an indicator of weight change? Obesity (Silver Spring, Md.) 27 18535557
2024 p21-activated kinase 4 counteracts PKA-dependent lipolysis by phosphorylating FABP4 and HSL. Nature metabolism 26 38216738
2015 Expression of FABP4, adipsin and adiponectin in Paneth cells is modulated by gut Lactobacillus. Scientific reports 26 26687459
2024 The Effects of FABP4 on Cardiovascular Disease in the Aging Population. Current atherosclerosis reports 25 38698167
2023 FABP4 Regulates Cell Proliferation, Stemness, Apoptosis, and Glycolysis in Colorectal Cancer via Modulating ROS/ERK/mTOR Pathway. Discovery medicine 25 37272103
2020 Independent and Distinct Associations of FABP4 and FABP5 With Metabolic Parameters in Type 2 Diabetes Mellitus. Frontiers in endocrinology 24 33071982
2019 Expression and correlation of Chemerin and FABP4 in peripheral blood of gestational diabetes mellitus patients. Experimental and therapeutic medicine 24 31897106
2016 Altered CSNK1E, FABP4 and NEFH protein levels in the dorsolateral prefrontal cortex in schizophrenia. Schizophrenia research 24 27236410
2024 FABP4-mediated lipid accumulation and lipolysis in tumor-associated macrophages promote breast cancer metastasis. eLife 23 39513934
2023 Endothelial-derived FABP4 constitutes the majority of basal circulating hormone and regulates lipolysis-driven insulin secretion. JCI insight 23 37279064
2017 FABP4 and Cardiovascular Events in Peripheral Arterial Disease. Angiology 23 28847153
2020 Circulating FABP4, nesfatin-1, and osteocalcin concentrations in women with gestational diabetes mellitus: a meta-analysis. Lipids in health and disease 22 32861247
2020 FABP4 inhibitor attenuates inflammation and endoplasmic reticulum stress of islet in leptin receptor knockout rats. European review for medical and pharmacological sciences 22 33378030
2024 Gut microbiota-derived acetic acids promoted sepsis-induced acute respiratory distress syndrome by delaying neutrophil apoptosis through FABP4. Cellular and molecular life sciences : CMLS 21 39453486
2023 Identification of Andrographolide as a novel FABP4 inhibitor for osteoarthritis treatment. Phytomedicine : international journal of phytotherapy and phytopharmacology 21 37354697
2023 Targeting Kindlin-2 in adipocytes increases bone mass through inhibiting FAS/PPARγ/FABP4 signaling in mice. Acta pharmaceutica Sinica. B 21 37969743
2018 Intermittent High Glucose Exacerbates A-FABP Activation and Inflammatory Response through TLR4-JNK Signaling in THP-1 Cells. Journal of immunology research 21 29850615
2018 Variation in the FABP4 gene affects carcass and growth traits in sheep. Meat science 21 30015163
2009 FABP4: a novel candidate gene for polycystic ovary syndrome. Endocrine 20 19844814
2021 The Low-Expression Variant of FABP4 Is Associated With Cardiovascular Disease in Type 1 Diabetes. Diabetes 19 34244239
2019 Relationships between visceral/subcutaneous adipose tissue FABP4 expression and coronary atherosclerosis in patients with metabolic syndrome. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 19 31927390
2022 Microglial FABP4-UCP2 Axis Modulates Neuroinflammation and Cognitive Decline in Obese Mice. International journal of molecular sciences 18 35457171
2016 Ectopical expression of FABP4 gene can induce bovine muscle-derived stem cells adipogenesis. Biochemical and biophysical research communications 18 27856250
2024 Islet-Resident Memory T Cells Orchestrate the Immunopathogenesis of Type 1 Diabetes through the FABP4-CXCL10 Axis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 17 38884133
2024 Novel FABP4+C1q+ macrophages enhance antitumor immunity and associated with response to neoadjuvant pembrolizumab and chemotherapy in NSCLC via AMPK/JAK/STAT axis. Cell death & disease 16 39353883
2023 Fatty acid-binding protein-4 (FABP4) and matrix metalloproteinase-9 (MMP9) as predictive values for nonalcoholic steatohepatitis (NASH). Lipids in health and disease 16 36609276
2023 Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer. BMC medicine 16 37833736
2022 Discovery of Cobimetinib as a novel A-FABP inhibitor using machine learning and molecular docking-based virtual screening. RSC advances 16 35520131
2018 Extracellular FABP4 uptake by endothelial cells is dependent on cytokeratin 1 expression. Biochimica et biophysica acta. Molecular and cell biology of lipids 16 30521939
2018 FABP4 accelerates glioblastoma cell growth and metastasis through Wnt10b signalling. European review for medical and pharmacological sciences 16 30536325
2024 FABP4 Enhances Lipidic and Fibrotic Cardiac Structural and Ca2+ Dynamic Changes. Circulation. Arrhythmia and electrophysiology 15 39212041
2024 Inhibition of the RXRA-PPARα-FABP4 signaling pathway alleviates vascular cellular aging by an SGLT2 inhibitor in an atherosclerotic mice model. Science China. Life sciences 15 39225895
2022 SIRT5 promotes non-small cell lung cancer progression by reducing FABP4 acetylation level. Neoplasma 15 35603953
2021 PXR-mediated expression of FABP4 promotes valproate-induced lipid accumulation in HepG2 cells. Toxicology letters 15 33901630
2025 FABP4 inhibition suppresses bone resorption and protects against postmenopausal osteoporosis in ovariectomized mice. Nature communications 14 40360512
2024 Fatty acid binding protein 4 (FABP4) induces chondrocyte degeneration via activation of the NF-κb signaling pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 14 38095503
2019 FABP4 levels in hypothyroidism and its relationship with subclinical atherosclerosis. Turkish journal of medical sciences 14 31651119
2024 Upregulation of FABP4 induced inflammation in the pathogenesis of chronic tendinopathy. Journal of orthopaedic translation 13 39007036
2024 Altered lipid metabolism promoting cardiac fibrosis is mediated by CD34+ cell-derived FABP4+ fibroblasts. Experimental & molecular medicine 13 39198543
2022 Comprehensive analysis of the immune implication of FABP4 in colon adenocarcinoma. PloS one 13 36264920
2021 Oleanolic acid derivative HA-20 inhibits adipogenesis in a manner involving PPARγ-FABP4/aP2 pathway. Journal of molecular endocrinology 13 33666565
2014 Lipocalin-2, A-FABP and inflammatory markers in relation to flow-mediated vasodilatation in patients with essential hypertension. Clinical and experimental hypertension (New York, N.Y. : 1993) 13 24491219
2012 Enhanced A-FABP expression in visceral fat: potential contributor to the progression of NASH. Clinical and molecular hepatology 13 23091808
2025 Targeting FABP4 to Inhibit AGEs-RAGE/NF-κB Signalling Effectively Ameliorates Nucleus Pulposus Dysfunction and Angiogenesis in Obesity-Related Intervertebral Disc Degeneration. Cell proliferation 12 40090836
2024 Fatty acid binding to the human transport proteins FABP3, FABP4, and FABP5 from a Ligand's perspective. The Journal of biological chemistry 12 38777142
2014 Small molecule inhibitors of human adipocyte fatty acid binding protein (FABP4). Medicinal chemistry (Shariqah (United Arab Emirates)) 12 24024500
2013 Circulating FABP4 and FABP5 levels are differently linked to OSA severity and treatment. Sleep 12 24293757
2024 FABP4 facilitates epithelial-mesenchymal transition via elevating CD36 expression in glioma cells. Neoplasia (New York, N.Y.) 11 39243502
2022 FABP4 and I-FABP Levels in Pregnant Women Are Associated with Body Mass Index but Not Gestational Diabetes. Journal of diabetes research 11 35647197
2022 Inhibition of FABP4 attenuates cardiac fibrosis through inhibition of NLRP3 inflammasome activation. Iranian journal of basic medical sciences 11 36311201
2020 Elevated expression of FABP4 is associated with disease activity in rheumatoid arthritis patients. Biomarkers in medicine 11 33151094
2025 Targeting FABP4/UCP2 axis to overcome cetuximab resistance in obesity-driven CRC with drug-tolerant persister cells. Translational oncology 10 39823981

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