Affinage

RBP4

Retinol-binding protein 4 · UniProt P02753

Length
201 aa
Mass
23.0 kDa
Annotated
2026-04-28
100 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RBP4 is a lipocalin-family retinol transport protein that functions both as the principal carrier of retinol in the circulation and as a signaling molecule that activates innate immune and metabolic pathways in diverse tissues. Synthesized predominantly by hepatocytes, RBP4 is stabilized in the circulation by transthyretin (TTR), which prevents its glomerular filtration; TTR knockdown reduces circulating RBP4 by 80–95% and improves insulin sensitivity (PMID:25524914), while Rbp4-knockout mice accumulate retinol in the liver but lack serum retinol and develop photoreceptor degeneration, demonstrating that RBP4 is essential for hepatic retinol mobilization (PMID:26974396). RBP4 delivers retinol to peripheral tissues via the receptor STRA6 and to the liver/intestine via RBPR2 (PMID:23105095), and dominant-negative RBP4 mutations that increase STRA6 affinity while abolishing retinol binding cause congenital ocular malformations in humans (PMID:25910211). Beyond retinol transport, RBP4 acts as an adipokine/hepatokine that activates antigen-presenting cells through MyD88-dependent JNK/ERK/p38/NF-κB signaling to drive adipose tissue inflammation and insulin resistance (PMID:24606904, PMID:26936962), engages STRA6 to transduce JAK2/STAT3 signaling in muscle and colon (PMID:39031684, PMID:28689994), and stimulates vascular smooth muscle cell proliferation through ERK1/2 and JAK2/STAT3 pathways (PMID:24888764, PMID:35082965).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2009 Medium

    Establishing transcriptional regulation of RBP4: it was unknown how glucagon/cAMP controlled RBP4 expression; Hmga1-knockout mice revealed that HMGA1 is required for basal and cAMP-induced RBP4 transcription, linking hormonal signaling to RBP4 levels.

    Evidence Hmga1-knockout mice with glucagon challenge, qPCR, Western blot, GLUT4/Akt readouts in muscle and fat

    PMID:19460132

    Open questions at the time
    • Single-lab finding without chromatin-level confirmation of HMGA1 occupancy at the Rbp4 promoter
    • Other transcriptional regulators of RBP4 not addressed
  2. 2012 High

    Identifying how liver and intestine take up RBP4-bound retinol: RBPR2 was discovered as a second RBP4 receptor structurally related to STRA6 that mediates retinol uptake in hepatic and intestinal cells, resolving the puzzle of retinol delivery to STRA6-negative tissues.

    Evidence Cell transfection with RBPR2, receptor binding assays, knockdown, retinol transport reconstitution

    PMID:23105095

    Open questions at the time
    • RBPR2 crystal structure not determined
    • In vivo RBPR2 knockout not yet performed at this time
  3. 2013 High

    Developing pharmacological tools to lower circulating RBP4: the non-retinoid antagonist A1120 was shown to bind RBP4 with high affinity and disrupt the RBP4–TTR interaction, reducing serum RBP4 by ~75% without RAR agonism, establishing proof-of-concept for therapeutic RBP4 targeting.

    Evidence In vitro binding and TTR interaction assays, in vivo dosing in Abca4−/− mice with biochemical and electrophysiological endpoints

    PMID:23211825

    Open questions at the time
    • Metabolic efficacy of A1120 not assessed in this study
    • Long-term safety and off-target effects not characterized
  4. 2014 High

    Revealing RBP4 as an immunomodulatory adipokine: it was unclear how elevated RBP4 caused insulin resistance; adoptive transfer experiments demonstrated that RBP4 directly activates antigen-presenting cells via JNK to drive Th1 CD4+ T cell responses, adipose tissue inflammation, and systemic insulin resistance.

    Evidence RBP4-overexpressing transgenic mice, adoptive transfer of APCs into wild-type recipients, JNK inhibition, glucose/insulin tolerance tests

    PMID:24606904

    Open questions at the time
    • Identity of the RBP4 receptor on APCs not established
    • Whether retinol loading of RBP4 is required for APC activation not tested
  5. 2014 High

    Demonstrating TTR as a critical stabilizer of circulating RBP4 with metabolic consequences: TTR antisense knockdown reduced circulating RBP4 by 80–95% and improved whole-body insulin sensitivity by hyperinsulinemic clamp, establishing that TTR-dependent RBP4 stabilization is necessary for metabolic dysfunction.

    Evidence TTR antisense oligonucleotides in ob/ob and HFD mice, hyperinsulinemic-euglycemic clamp, tissue glucose uptake measurements

    PMID:25524914

    Open questions at the time
    • Whether TTR knockdown benefits are entirely RBP4-dependent or partly due to loss of TTR itself
    • Renal handling kinetics of free RBP4 not quantified
  6. 2015 High

    Linking human RBP4 mutations to congenital eye disease: dominant-negative RBP4 missense mutations were found to abolish retinol binding yet increase STRA6 affinity, competitively blocking retinol delivery and causing ocular malformations through a maternal-effect mechanism.

    Evidence Family-based mutation identification, retinol and STRA6 binding assays on recombinant mutant proteins

    PMID:25910211

    Open questions at the time
    • Structural basis of increased STRA6 affinity by mutant RBP4 not resolved
    • Whether other tissues are affected in mutation carriers not fully assessed
  7. 2016 High

    Resolving the hepatocyte as the dominant source of circulating RBP4: liver-specific RBP4 knockout eliminated detectable circulating RBP4 despite intact adipose expression, definitively establishing hepatocytes—not adipocytes—as the principal systemic source.

    Evidence Hepatocyte-specific Cre-lox Rbp4 knockout mice, serum RBP4 measurement, adipose tissue expression analysis

    PMID:27797907

    Open questions at the time
    • Paracrine role of adipocyte-derived RBP4 within adipose tissue not excluded
    • Whether adipose RBP4 contributes to local inflammation independently of circulating pool not tested
  8. 2016 High

    Delineating the innate immune signaling pathway of RBP4: MyD88 knockout macrophages failed to respond to RBP4, establishing that RBP4 activates macrophages through MyD88-dependent MAPK/NF-κB signaling, and CTLA4-Ig blockade of costimulation in vivo reversed RBP4-driven insulin resistance.

    Evidence MyD88-KO macrophages, pathway inhibitors, CTLA4-Ig in RBP4-overexpressing mice, cytokine and metabolic readouts

    PMID:26936962

    Open questions at the time
    • The specific pattern-recognition receptor upstream of MyD88 that senses RBP4 is not identified
    • Whether TLR4 or another TLR mediates the signal is unresolved
  9. 2016 High

    Demonstrating the essentiality of RBP4 for retinol mobilization and ocular integrity: Rbp4-knockout mice had undetectable serum retinol despite hepatic retinol accumulation and developed severe photoreceptor degeneration and choroidal atrophy.

    Evidence Rbp4-KO mice (C57BL/6), electroretinography, histology, serum/liver retinol quantification

    PMID:26974396

    Open questions at the time
    • Whether dietary retinol supplementation can rescue ocular phenotype not tested
    • Contribution of retinoic acid versus retinol signaling to the degeneration not dissected
  10. 2017 High

    Establishing STRA6 as a cytokine receptor for RBP4 in cancer and muscle: RBP4–STRA6 interaction activates JAK2/STAT3 to maintain colon cancer stem cells and promote denervation-induced muscle atrophy; pharmacological RBP4 antagonist A1120 blocked muscle atrophy in vivo.

    Evidence STRA6/RBP4 knockdown in colon cancer cells and C2C12 myotubes, xenografts, denervation model, siRNA and inhibitor epistasis, A1120 rescue

    PMID:28689994 PMID:39031684

    Open questions at the time
    • Whether JAK2/STAT3 activation is direct (STRA6 kinase-independent scaffolding) or requires additional co-receptors
    • Structural basis of STRA6 cytokine signaling versus transport function not resolved
  11. 2018 High

    Expanding the ligand repertoire of RBP4: high-resolution crystal structures revealed that plasma RBP4 binds fatty acids (palmitate, laurate) in its retinol-binding pocket, indicating RBP4 is not exclusively a retinol carrier.

    Evidence X-ray crystallography at 1.5 Å from plasma, urine, and amniotic fluid RBP4; mass spectrometry confirmation

    PMID:29414511

    Open questions at the time
    • Functional consequence of fatty acid binding on STRA6 or RBPR2 signaling not tested
    • Relative occupancy of retinol versus fatty acid in vivo not determined
  12. 2020 Medium

    Demonstrating that RBP4 regulates adipocyte lipolysis both directly and through macrophage-derived TNFα, linking RBP4-driven immune activation to lipid metabolic dysfunction.

    Evidence RBP4 treatment of human adipocytes, conditioned media from RBP4-activated macrophages, lipolysis and cytokine assays

    PMID:32167208

    Open questions at the time
    • Receptor mediating direct lipolytic effect on adipocytes not identified
    • In vivo lipolysis contribution of RBP4 not quantified
  13. 2020 Medium

    Revealing a diabetic-specific post-translational mechanism: O-GlcNAcylation of RBPR2 by OGT under high-glucose conditions impairs hepatic RBP4 uptake, contributing to RBP4 overproduction; OGT silencing restored retinol homeostasis.

    Evidence Immunoprecipitation for O-GlcNAc-RBPR2, OGT silencing, CRBP1 transfection rescue in db/db and ob/ob mice and high-glucose hepatocytes

    PMID:33065162

    Open questions at the time
    • Specific O-GlcNAcylation site(s) on RBPR2 not mapped
    • Whether this mechanism operates in human diabetic liver not confirmed
  14. 2022 Medium

    Identifying an exosomal RBP4 feedback loop in NAFLD: hepatocyte-derived exosomal RBP4 polarizes Kupffer cells to M1 via NOX2/ROS/NF-κB, which secrete TNFα that activates STAT3 in hepatocytes to further upregulate RBP4, establishing a self-amplifying inflammatory circuit.

    Evidence Serum exosome characterization, Kupffer cell polarization assays, NOX2/NF-κB inhibition, TNFα treatment, in vivo RBP4 injection in HFD mice

    PMID:36572267

    Open questions at the time
    • Whether exosomal versus free RBP4 has distinct receptor engagement not compared
    • Feedback loop not validated by genetic interruption in vivo

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of the cell-surface receptor mediating RBP4's activation of antigen-presenting cells and macrophages (upstream of MyD88) remains unknown, and the structural basis for STRA6's dual function as retinol transporter and cytokine receptor has not been determined.
  • No receptor for RBP4 on macrophages/APCs identified
  • No structural model of STRA6 in signaling versus transport mode
  • Relative physiological importance of retinol-dependent versus retinol-independent RBP4 signaling not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 6 GO:0140104 molecular carrier activity 4 GO:0008289 lipid binding 1
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-168256 Immune System 4 R-HSA-1643685 Disease 3 R-HSA-382551 Transport of small molecules 3
Partners
JAK2MYD88RBPR2STAT3STRA6TTR
Complex memberships
RBP4–TTR complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 RBPR2, a novel retinol transporter structurally related to STRA6, was identified as the liver and intestinal receptor for RBP4. Expression of RBPR2 in cultured cells confers high-affinity RBP4 binding and retinol transport, and RBPR2 knockdown reduces RBP4 binding and retinol transport. Cell transfection, receptor binding assay, knockdown, in vitro retinol transport assay The Journal of biological chemistry High 23105095
2018 Human plasma RBP4 binds fatty acids (palmitic and lauric acid) in its hydrophobic ligand-binding pocket in addition to retinol, as determined by high-resolution crystal structures confirmed by mass spectrometry. X-ray crystallography (1.5 Å resolution), mass spectrometry Biochimica et biophysica acta. Molecular and cell biology of lipids High 29414511
2014 RBP4 causes adipose tissue inflammation and systemic insulin resistance by directly activating antigen-presenting cells (APCs) through a JNK-dependent pathway, which then elicits CD4 T cell Th1 polarization. Transfer of RBP4-activated APCs into normal mice is sufficient to induce AT inflammation and insulin resistance. RBP4-overexpressing transgenic mice, adoptive transfer of APCs, JNK pathway inhibition, glucose/insulin tolerance tests Cell metabolism High 24606904
2016 RBP4-induced macrophage antigen presentation and T-cell activation requires MyD88 and downstream MAPK (JNK, ERK, p38) and NF-κB pathways; in MyD88-deficient macrophages RBP4 fails to stimulate TNF, IL-12, and IL-6 secretion. In vivo blockade of antigen presentation with CTLA4-Ig reduces AT inflammation and improves insulin resistance in RBP4-overexpressing mice. MyD88 knockout macrophages, pathway inhibitors, CTLA4-Ig in vivo blockade, cytokine measurement, insulin/glucose tolerance tests Diabetes High 26936962
2016 Hepatocytes are the principal source of circulating RBP4; liver-specific RBP4 knockout mice have undetectable circulating RBP4 despite intact adipose tissue RBP4 expression and secretion, even in diet-induced insulin resistance. Hepatocyte-specific Cre-lox RBP4 knockout mice, circulating RBP4 measurement, adipose tissue RBP4 expression analysis Diabetes High 27797907
2015 Dominant-negative missense mutations in RBP4 greatly reduce retinol binding but paradoxically increase affinity for the cell-surface receptor STRA6, thereby competitively blocking retinol delivery from wild-type RBP4 to fetal and placental tissues and causing ocular malformations. Missense mutation identification in families, retinol binding assays, STRA6 binding assays, functional characterization of mutant proteins Cell High 25910211
2014 Circulating transthyretin (TTR) stabilizes RBP4 by preventing its glomerular filtration; antisense oligonucleotide knockdown of TTR reduces circulating RBP4 by 80-95% and improves insulin sensitivity, hepatic glucose production suppression, and muscle glucose uptake in obese mice. TTR antisense oligonucleotides in ob/ob and HFD mice, hyperinsulinemic-euglycemic clamp, glucose uptake measurement, insulin signaling assays Diabetes High 25524914
2017 RBP4 activates STRA6 as a cytokine receptor to transduce a JAK2-STAT3 signaling cascade, which promotes cancer stem cell maintenance and tumor initiation in colon cancer; downregulation of STRA6 or RBP4 decreases cancer stem cell fraction and sphere/tumor initiation frequency. STRA6/RBP4 knockdown in colon cancer cells, sphere formation assay, xenograft mouse model, flow cytometry for cancer stem cells Stem cell reports Medium 28689994
2017 Retinol-bound (holo-)RBP4 activates STRA6 and downstream JAK2/STAT3 signaling to promote denervation-induced muscle atrophy and fat infiltration; inhibition of STRA6, JAK2, or STAT3 (by siRNA or inhibitors) reduces Atrogin-1 and MuRF1 upregulation and protects myotube diameter. Pharmacological RBP4 antagonist A1120 inhibits this pathway and ameliorates muscle atrophy in vivo. RBP4 knockout mice, intramuscular injection of holo- vs apo-RBP4, siRNA knockdown of STRA6/JAK2/STAT3, specific pathway inhibitors, C2C12 myotube assays, denervation model, A1120 pharmacological blockade Journal of cachexia, sarcopenia and muscle High 39031684
2017 Apo-RBP4 (retinol-free form) functions as a ligand that activates STRA6 and downstream JAK2/STAT5 cascade, leading to SOCS3 upregulation, decreased phosphorylation of IR and IRS1, attenuated GLUT4 translocation, and insulin resistance. Co-immunoprecipitation confirmed prolonged apo-RBP4/STRA6 interaction compared to holo-RBP4. Co-immunoprecipitation, Western blotting, immunofluorescence, in vivo apo-RBP4 injection in pregnant rats, primary human adipocyte culture Archives of gynecology and obstetrics Medium 28528355
2020 RBP4 directly stimulates basal lipolysis in human adipocytes in vitro; RBP4-activated macrophages produce TNFα that markedly increases basal lipolysis and impairs insulin-mediated lipolysis suppression in adipocytes. RBP4 treatment of human adipocytes, conditioned media from RBP4-activated macrophages, lipolysis assays, cytokine measurement FASEB journal Medium 32167208
2009 HMGA1 is a transcriptional regulator required for basal and cAMP-induced RBP4 gene and protein expression; glucagon (via cAMP) upregulates both HMGA1 and RBP4 in wild-type mice, while Hmga1-knockout mice show severely attenuated RBP4 expression correlated with increased GLUT4 and Akt activation in muscle and fat. Hmga1-knockout mouse model, glucagon administration, qPCR, Western blotting, GLUT4 and Akt assays in multiple tissues BMC biology Medium 19460132
2013 Non-retinoid RBP4 antagonist A1120 binds RBP4 with high affinity and inhibits the RBP4-TTR interaction, reducing serum RBP4 by 75% in mice and correlating with reduction in visual cycle retinoids and ocular lipofuscin bisretinoids, without acting as a RARα agonist unlike fenretinide. In vitro RBP4 binding assay, RBP4-TTR interaction assay, RPE microsome isomerohydrolase assay, in vivo mouse dosing (Abca4−/− model), biochemical and electrophysiological analysis Investigative ophthalmology & visual science High 23211825
2022 Exosomal RBP4 from hepatocytes promotes M1-like polarization of Kupffer cells via NOX2/ROS/NF-κB pathway, which then induces TNFα secretion that activates STAT3 in hepatocytes to further upregulate RBP4 transcription, creating a positive feedback loop promoting NAFLD. Serum exosome characterization, Kupffer cell polarization assays, NOX2/NF-κB inhibition, TNFα treatment of hepatocytes, intravenous RBP4 injection in HFD mice, lipogenesis gene expression Free radical biology & medicine Medium 36572267
2016 Rbp4-deficient mice in the C57BL/6 background accumulate retinol in the liver but have undetectable serum retinol, demonstrating that RBP4 is critical for mobilization of retinol from hepatic storage pools; these mice develop severe ocular phenotypes including photoreceptor degeneration, loss of choroid, and persistent hyaloid artery. Rbp4-knockout mouse model, electroretinography, histological analysis, retinol quantification in serum and liver Laboratory investigation High 26974396
2018 A canine RBP4 K12del mutation near the N-terminus disrupts RBP4 folding in vivo, decreasing its secretion from hepatocytes to serum, and causes ocular malformations only when both dam and offspring carry the deletion homozygously, demonstrating recessive maternal inheritance through impaired sequential retinol transfer across the placenta. Whole genome sequencing, in vivo secretion assays, NMR structural analysis (implied by Permi co-author), maternal-fetal transmission analysis Cell reports Medium 29847795
2013 IL-1β downregulates RBP4 mRNA expression and secretion in human adipocytes in a time- and dose-dependent manner, mediated through the IL-1 receptor and NF-κB pathway; IL-1 receptor blocking antibody and NF-κB inhibitors reverse this effect. Human SGBS and primary adipocytes treated with recombinant cytokines and macrophage conditioned media, qPCR, ELISA, IL-1R blocking antibody, NF-κB inhibitors (CAPE, SC-514) PloS one Medium 23460908
2020 O-GlcNAcylation of RBPR2 (the liver RBP4 receptor) by OGT disrupts retinol cascade in diabetic liver, reducing RBP4 uptake and contributing to RBP4 overproduction; OGT silencing reverses cellular retinol dyshomeostasis and RBP4 overproduction in high-glucose-treated hepatocytes. CRBP1 gene transfection also reverses RBP4 overproduction. Immunoprecipitation for O-GlcNAc-modified RBPR2, dual fluorescence, OGT silencing, CRBP1 transfection, Western blot in db/db and ob/ob mice and high-glucose hepatocytes Metabolism: clinical and experimental Medium 33065162
2023 Succinate triggers M2 polarization of macrophages via SUCNR1, which promotes release of RBP4 from macrophages; secreted RBP4 then regulates endothelial tip cell formation and pathological angiogenesis via VEGFR2 signaling. Choroidal neovascularization and oxygen-induced retinopathy mouse models, macrophage polarization assays, endothelial cell migration/invasion/tubulation assays, SUCNR1 and VEGFR2 pathway analysis Journal of neuroinflammation Medium 38129891
2014 RBP4 promotes proliferation of vascular smooth muscle cells (VSMCs) in the setting of hyperinsulinemia via activation of the MAPK/ERK1/2 signaling pathway; ERK1/2 inhibitor PD98059 blocks RBP4-induced VSMC proliferation, while JAK2 inhibition does not. Rat aortic smooth muscle cell (RASMC) culture, RBP4 treatment, ERK1/2 inhibitor PD98059, JAK2 inhibitor AG490, Western blot for p-ERK1/2 and p-JAK2, proliferation assay Endocrine Medium 24888764
2022 RBP4 promotes proliferation and migration of vascular smooth muscle cells via the JAK2/STAT3 signaling pathway; RBP4 overexpression increases JAK2, STAT3, cyclinD1, and Bcl-2 levels, while vitamin D supplementation lowers these markers and inhibits RBP4/JAK2/STAT3-induced VSMC proliferation. RBP4 overexpression plasmid transfection in VSMCs, vitamin D treatment, Western blot for JAK2/STAT3/cyclinD1/Bcl-2, rat diabetic atherosclerosis model Oxidative medicine and cellular longevity Medium 35082965
2018 RBP4 overexpression in trophoblast cells (HTR8/SVneo) enhances proliferation and invasion via activation of PI3K/AKT signaling; RBP4 knockdown reduces proliferation, invasion, and MMP expression and suppresses PI3K/AKT phosphorylation. RBP4 overexpression and siRNA knockdown in HTR8/SVneo cells, CCK-8 proliferation assay, transwell invasion assay, Western blot for p-PI3K and p-AKT Molecular medicine reports Medium 30015949

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 RBP4 activates antigen-presenting cells, leading to adipose tissue inflammation and systemic insulin resistance. Cell metabolism 236 24606904
2011 RBP4: a controversial adipokine. European journal of endocrinology 180 21835764
2007 Shortcomings in methodology complicate measurements of serum retinol binding protein (RBP4) in insulin-resistant human subjects. Diabetologia 158 17294166
2021 Biological Functions of RBP4 and Its Relevance for Human Diseases. Frontiers in physiology 148 33790810
2005 Characterization of transgenic Arabidopsis plants overexpressing GR-RBP4 under high salinity, dehydration, or cold stress. Journal of experimental botany 117 16207746
2012 Liver retinol transporter and receptor for serum retinol-binding protein (RBP4). The Journal of biological chemistry 114 23105095
2013 Plasma retinol-binding protein 4 (RBP4) levels and risk of coronary heart disease: a prospective analysis among women in the nurses' health study. Circulation 105 23584360
2017 RBP4-STRA6 Pathway Drives Cancer Stem Cell Maintenance and Mediates High-Fat Diet-Induced Colon Carcinogenesis. Stem cell reports 89 28689994
2009 Discriminated benefits of a Mediterranean dietary pattern within a hypocaloric diet program on plasma RBP4 concentrations and other inflammatory markers in obese subjects. Endocrine 79 19816812
2013 A1120, a nonretinoid RBP4 antagonist, inhibits formation of cytotoxic bisretinoids in the animal model of enhanced retinal lipofuscinogenesis. Investigative ophthalmology & visual science 78 23211825
2016 Hepatocytes Are the Principal Source of Circulating RBP4 in Mice. Diabetes 71 27797907
2008 Effect of exercise training on A-FABP, lipocalin-2 and RBP4 levels in obese women. Clinical endocrinology 68 18710473
2008 Isoforms of retinol binding protein 4 (RBP4) are increased in chronic diseases of the kidney but not of the liver. Lipids in health and disease 63 18752671
2016 Antigen Presentation and T-Cell Activation Are Critical for RBP4-Induced Insulin Resistance. Diabetes 59 26936962
2015 Biochemical Basis for Dominant Inheritance, Variable Penetrance, and Maternal Effects in RBP4 Congenital Eye Disease. Cell 57 25910211
2018 Adipokine RBP4 drives ovarian cancer cell migration. Journal of ovarian research 52 29642915
2014 The relationship of novel adipokines, RBP4 and omentin-1, with carotid atherosclerosis severity and vulnerability. Atherosclerosis 52 24956535
2020 RBP4 increases lipolysis in human adipocytes and is associated with increased lipolysis and hepatic insulin resistance in obese women. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 50 32167208
2009 Methylation of CLDN6, FBN2, RBP1, RBP4, TFPI2, and TMEFF2 in esophageal squamous cell carcinoma. Oncology reports 49 19288010
2006 Elevated serum RBP4 is associated with insulin resistance in women with polycystic ovary syndrome. Endocrine 49 17526940
2016 Assessment of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Retinol-Binding Protein 4 (RBP4) in Type 2 Diabetic Patients with Nephropathy. Biomarker insights 48 26917947
2010 Retinol binding protein 4 (RBP4) is primarily associated with adipose tissue mass in children. International journal of pediatric obesity : IJPO : an official journal of the International Association for the Study of Obesity 48 20950077
2018 Childhood retinol-binding protein 4 (RBP4) levels predicting the 10-year risk of insulin resistance and metabolic syndrome: the BCAMS study. Cardiovascular diabetology 47 29759068
2009 The cAMP-HMGA1-RBP4 system: a novel biochemical pathway for modulating glucose homeostasis. BMC biology 46 19460132
2018 Human plasma retinol-binding protein (RBP4) is also a fatty acid-binding protein. Biochimica et biophysica acta. Molecular and cell biology of lipids 45 29414511
2014 Transthyretin Antisense Oligonucleotides Lower Circulating RBP4 Levels and Improve Insulin Sensitivity in Obese Mice. Diabetes 45 25524914
2022 Exosomal RBP4 potentiated hepatic lipid accumulation and inflammation in high-fat-diet-fed mice by promoting M1 polarization of Kupffer cells. Free radical biology & medicine 44 36572267
2018 Liver-secreted RBP4 does not impair glucose homeostasis in mice. The Journal of biological chemistry 44 30126844
1989 Regional mapping of RBP4 to 10q23----q24 and RBP1 to 3q21----q22 in man. Somatic cell and molecular genetics 43 2928844
2010 Case-control analysis of SNPs in GLUT4, RBP4 and STRA6: association of SNPs in STRA6 with type 2 diabetes in a South Indian population. PloS one 41 20625434
2015 Variants in RBP4 and AR genes modulate age at onset in familial amyloid polyneuropathy (FAP ATTRV30M). European journal of human genetics : EJHG 38 26286643
2008 Elevated concentrations of retinol-binding protein-4 (RBP-4) in gestational diabetes mellitus: negative correlation with soluble vascular cell adhesion molecule-1 (sVCAM-1). Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 38 18584408
2010 Association of retinol-binding protein-4 (RBP4) with lipid parameters in obese women. Obesity surgery 37 20544399
2020 Novel adipokine associated with OA: retinol binding protein 4 (RBP4) is produced by cartilage and is correlated with MMPs in osteoarthritis patients. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 36 32095874
2012 Contrasting effects of type 2 and type 1 diabetes on plasma RBP4 levels: the significance of transthyretin. IUBMB life 34 23129325
2021 RBP4 Is Associated With Insulin Resistance in Hyperuricemia-Induced Rats and Patients With Hyperuricemia. Frontiers in endocrinology 30 34177800
2016 Severe ocular phenotypes in Rbp4-deficient mice in the C57BL/6 genetic background. Laboratory investigation; a journal of technical methods and pathology 29 26974396
2008 Effect of RBP4 gene variants on circulating RBP4 concentration and type 2 diabetes in a Chinese population. Diabetic medicine : a journal of the British Diabetic Association 29 18199128
2015 Association of RBP4 genetic variants with childhood obesity and cardiovascular risk factors. Pediatric diabetes 28 26611784
2011 High liver RBP4 protein content is associated with histological features in patients with genotype 1 chronic hepatitis C and with nonalcoholic steatohepatitis. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 28 21324757
2008 Decreased hepatic RBP4 secretion is correlated with reduced hepatic glucose production but is not associated with insulin resistance in patients with liver cirrhosis. Clinical endocrinology 28 18466349
2012 Quantitative measurement of full-length and C-terminal proteolyzed RBP4 in serum of normal and insulin-resistant humans using a novel mass spectrometry immunoassay. Endocrinology 27 22253430
2011 Human RBP4 adipose tissue expression is gender specific and influenced by leptin. Clinical endocrinology 27 21039728
2016 Retinol-binding protein 4 (RBP4) as the causative factor and marker of vascular injury related to insulin resistance. Postepy higieny i medycyny doswiadczalnej (Online) 26 28026829
2014 Association of urinary RBP4 with insulin resistance, inflammation, and microalbuminuria. European journal of endocrinology 26 24994759
2010 Associations of metabolic factors, especially serum retinol-binding protein 4 (RBP4), with blood pressure in Japanese--the Tanno and Sobetsu study. Endocrine journal 25 20798476
2018 Components of metabolic syndrome in relation to plasma levels of retinol binding protein 4 (RBP4) in a cohort of people aged 65 years and older. Journal of endocrinological investigation 24 29524177
2018 RBP4 regulates trophoblastic cell proliferation and invasion via the PI3K/AKT signaling pathway. Molecular medicine reports 24 30015949
2014 Proteomic Analysis of RBP4/Vitamin A in Children with Cleft Lip and/or Palate. Journal of dental research 24 24695672
2012 Serum FGF21 and RBP4 levels in patients with chronic hepatitis C. Scandinavian journal of gastroenterology 24 22670657
2017 Increased retinol-free RBP4 contributes to insulin resistance in gestational diabetes mellitus. Archives of gynecology and obstetrics 23 28528355
2021 LncRNA PTGS2 regulates islet β-cell function through the miR-146a-5p/RBP4 axis and its diagnostic value in type 2 diabetes mellitus. American journal of translational research 22 34786060
2017 Dietary weight loss-induced changes in RBP4, FFA, and ACE predict weight regain in people with overweight and obesity. Physiological reports 21 29122953
2016 Vitamin A deficiency due to bi-allelic mutation of RBP4: There's more to it than meets the eye. Ophthalmic genetics 21 27892788
2009 Association of RBP4 gene variants and serum HDL cholesterol levels in the Newfoundland population. Obesity (Silver Spring, Md.) 21 19893506
2024 RBP4 promotes denervation-induced muscle atrophy through STRA6-dependent pathway. Journal of cachexia, sarcopenia and muscle 20 39031684
2022 Green Coffee Bean Extract Normalize Obesity-Induced Alterations of Metabolic Parameters in Rats by Upregulating Adiponectin and GLUT4 Levels and Reducing RBP-4 and HOMA-IR. Life (Basel, Switzerland) 20 35629362
2020 The Role of Circulating RBP4 in the Type 2 Diabetes Patients with Kidney Diseases: A Systematic Review and Meta-Analysis. Disease markers 20 33082885
2019 The influence of Visfatin, RBP-4 and insulin resistance on bone mineral density in women with treated primary osteoporosis. Aging clinical and experimental research 20 31054116
2010 Non-additive effects of RBP4, ESR1 and IGF2 polymorphisms on litter size at different parities in a Chinese-European porcine line. Genetics, selection, evolution : GSE 20 20576168
2008 Effect of polymorphisms in the genes for LIF and RBP4 on litter size in two German pig lines. Reproduction in domestic animals = Zuchthygiene 20 18537906
2008 Human fetal adiponectin and retinol-binding protein (RBP)-4 levels in relation to birth weight and maternal obesity. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 20 19053019
2023 Succinate-induced macrophage polarization and RBP4 secretion promote vascular sprouting in ocular neovascularization. Journal of neuroinflammation 19 38129891
2020 Determination of FABP4, RBP4 and the MMP-9/NGAL complex in the serum of women with breast cancer. Oncology letters 19 33376518
2019 Relationships of SLC2A4, RBP4, PCK1, and PI3K Gene Polymorphisms with Gestational Diabetes Mellitus in a Chinese Population. BioMed research international 19 30805369
2012 Alterations in systemic concentrations of progesterone during the early luteal phase affect RBP4 expression in the bovine uterus. Reproduction, fertility, and development 19 22697121
2023 Shift work is associated with an increased risk of type 2 diabetes and elevated RBP4 level: cross sectional analysis from the OHSPIW cohort study. BMC public health 18 37312059
2012 Valproic acid downregulates RBP4 and elicits hypervitaminosis A-teratogenesis--a kinetic analysis on retinol/retinoic acid homeostatic system. PloS one 18 23028466
2022 The Effects of RBP4 and Vitamin D on the Proliferation and Migration of Vascular Smooth Muscle Cells via the JAK2/STAT3 Signaling Pathway. Oxidative medicine and cellular longevity 17 35082965
2020 Retinol and vitamin A metabolites accumulate through RBP4 and STRA6 changes in a psoriasis murine model. Nutrition & metabolism 17 31956331
2014 Increased RBP4 in a human model of activated anti-atherosclerotic and antiremodelling defences. European journal of clinical investigation 17 24739026
2014 Involvement of RBP4 in hyperinsulinism-induced vascular smooth muscle cell proliferation. Endocrine 17 24888764
2013 Metabolic syndrome, circulating RBP4, testosterone, and SHBG predict weight regain at 6 months after weight loss in men. Obesity (Silver Spring, Md.) 17 23408763
2013 Interleukin-1β downregulates RBP4 secretion in human adipocytes. PloS one 17 23460908
2022 Significantly Reduced Retinol Binding Protein 4 (RBP4) Levels in Critically Ill COVID-19 Patients. Nutrients 16 35631143
2018 Serum RBP4 positively correlates with triglyceride level but not with BMI, fat mass and insulin resistance in healthy obese and non-obese individuals. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 16 29786448
2014 A genetic polymorphism in RBP4 is associated with coronary artery disease. International journal of molecular sciences 16 25479076
2011 High plasma retinol binding protein 4 (RBP4) is associated with systemic inflammation independently of low RBP4 adipose expression and is normalized by transplantation in nonobese, nondiabetic patients with chronic kidney disease. Clinical endocrinology 16 21521262
2008 High circulating levels of RBP4 and mRNA levels of aP2, PGC-1alpha and UCP-2 predict improvement in insulin sensitivity following pioglitazone treatment of drug-naïve type 2 diabetic subjects. Journal of internal medicine 16 18324929
2021 A novel regulatory mechanism of geniposide for improving glucose homeostasis mediated by circulating RBP4. Phytomedicine : international journal of phytotherapy and phytopharmacology 14 34856473
2018 Involvement of RBP4 in Diabetic Atherosclerosis and the Role of Vitamin D Intervention. Journal of diabetes research 14 30186876
2017 Evaluation of insulin-like growth factor (IGF-1) and retinol binding protein (RBP-4) levels in patients with newly diagnosed pancreatic adenocarcinoma (PDAC). Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 14 28499807
2011 Circulating Nampt and RBP4 levels in patients with carotid stenosis undergoing carotid endarterectomy (CEA). Clinica chimica acta; international journal of clinical chemistry 14 21406189
2021 Systematic Quantification of Neurotrophic Adipokines RBP4, PEDF, and Clusterin in Human Cerebrospinal Fluid and Serum. The Journal of clinical endocrinology and metabolism 13 33484131
2020 Retinol-binding protein 4 (RBP4) and high sensitivity C-reactive protein (hs-CRP) levels in patients with diminished ovarian reserve (DOR): a cross-sectional study. Reproductive biology and endocrinology : RB&E 13 33198782
2019 Phenome-wide association study of TTR and RBP4 genes in 361,194 individuals reveals novel insights in the genetics of hereditary and wildtype transthyretin amyloidoses. Human genetics 13 31659433
2018 The preliminary association study of ADIPOQ, RBP4, and BCMO1 variants with polycystic ovary syndrome and with biochemical characteristics in a cohort of Polish women. Advances in medical sciences 13 29428584
2018 Maternal Inheritance of a Recessive RBP4 Defect in Canine Congenital Eye Disease. Cell reports 13 29847795
2017 Transgenic Mice Over-Expressing RBP4 Have RBP4-Dependent and Light-Independent Retinal Degeneration. Investigative ophthalmology & visual science 13 28813718
2016 Increased plasma RBP4 concentration in older hypertensives is related to the decreased kidney function and the number of antihypertensive drugs-results from the PolSenior substudy. Journal of the American Society of Hypertension : JASH 13 28038989
2024 Retinol-binding protein 4 (RBP4) circulating levels and gestational diabetes mellitus: a systematic review and meta-analysis. Frontiers in public health 12 38532976
2022 Effect of Upregulation of Transcription Factor TFDP1 Binding Promoter Activity Due to RBP4 g.36491960G>C Mutation on the Proliferation of Goat Granulosa Cells. Cells 12 35883591
2019 Correlation Between Tenofovir Drug Levels and the Renal Biomarkers RBP-4 and ß2M in the ION-4 Study Cohort. Open forum infectious diseases 12 30697570
2016 Association of RBP4 Genotype with Phenotypic Reproductive Traits of Sows. Genetics research international 12 26885398
2016 Association of BF, RBP4, and ESR2 Genotypes with Litter Size in an Autochthonous Pig Population. Animal biotechnology 12 27824510
2014 Significance of RBP4 in patients with gestational diabetes mellitus: a case-control study of Han Chinese women. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 12 24397358
2013 Gender dimorphic increase in RBP-4 and NGAL in children born after IVF: an epigenetic phenomenon? European journal of clinical investigation 12 23496280
2013 The effects of weight loss on FABP4 and RBP4 in obese women with metabolic syndrome. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 12 23979787
2020 Disruption of retinoid homeostasis induces RBP4 overproduction in diabetes: O-GlcNAcylation involved. Metabolism: clinical and experimental 11 33065162
2018 High resolution crystal structure data of human plasma retinol-binding protein (RBP4) bound to retinol and fatty acids. Data in brief 11 29900277