Affinage

ADIPOQ

Adiponectin · UniProt Q15848

Length
244 aa
Mass
26.4 kDa
Annotated
2026-06-09
100 papers in source corpus 19 papers cited in narrative 19 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

ADIPOQ encodes adiponectin (GBP28/apM1/Acrp30), an adipocyte-secreted, collagen-domain protein that acts as a systemic regulator of glucose and lipid metabolism, insulin sensitivity, and organismal healthspan (PMID:8947845, PMID:33904399). Originally purified from plasma as a gelatin-binding protein with a signal sequence, collagen-like repeats, and a globular C-terminal domain, it assembles into trimers, hexamers, and high-molecular-weight (HMW) oligomers, with interchain disulfide bonds through Cys-39/Cys-22 required for higher-order assembly (PMID:8947845, PMID:12496257, PMID:14522956). Oligomerization state dictates signaling output: trimers preferentially activate AMPK (Thr172 phosphorylation) in muscle, while hexameric and HMW forms drive NF-κB signaling via IκB-α degradation, and only hexamer/HMW species bind the receptor T-cadherin in a manner dependent on eukaryotic post-translational modification (PMID:12496257, PMID:12087086, PMID:14522956, PMID:15210937). Its principal metabolic action is suppression of hepatic glucose output — in vivo it reduces endogenous glucose production and downregulates the gluconeogenic enzymes PEPCK and G6Pase, sensitizing the liver to insulin (PMID:11479628, PMID:11748271). In muscle, adiponectin signaling supports IRS-1-associated PI3-kinase activity, FATP-1 expression, free fatty acid clearance, and AMPK/SIRT1/PGC-1α-driven mitochondrial biogenesis, as established by adiponectin and muscle-specific AdipoR1 knockouts (PMID:12068289, PMID:22492282). Intracellular signal transmission depends on the adaptor APPL1, which binds the AdipoR1 cytoplasmic domain, is recruited upon adiponectin stimulation, and links receptor engagement to lipid oxidation, glucose uptake, GLUT4 translocation (via Rab5), and cross-talk with insulin signaling (PMID:16622416). Adiponectin expression is regulated transcriptionally — suppressed by TNF-α and induced through a GPRC6A→cAMP/PKA→ERK/CREB→PPARγ axis by uncarboxylated osteocalcin — and its actions extend to context-dependent modulation of macrophage inflammation and lifespan extension (PMID:11246823, PMID:25562427, PMID:25392268, PMID:33904399).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1996 High

    Established the molecular identity and architecture of adiponectin, defining the structural basis for its oligomerization.

    Evidence Affinity purification from human plasma, N-terminal sequencing, peptide mapping, and reducing/non-reducing SDS-PAGE

    PMID:8947845

    Open questions at the time
    • Did not define receptors or signaling
    • Functional role of oligomers unaddressed at this stage
  2. 1999 Medium

    Mapped the gene to 3q27 and characterized its exon-intron and promoter structure, providing the genomic basis for transcriptional regulation.

    Evidence Genomic cloning and FISH chromosomal mapping with exon-intron boundary sequencing

    PMID:10095105 PMID:11162643

    Open questions at the time
    • No functional transcription factor identification
    • Promoter activity only shown in tissue culture
  3. 2001 High

    Identified the liver as a primary target and pinpointed suppression of hepatic gluconeogenesis as the dominant glucose-lowering mechanism, distinguishing it from peripheral glucose uptake.

    Evidence Recombinant protein injection in multiple diabetic mouse models, hepatocyte glucose-production assays, and pancreatic euglycemic clamp with isotopic tracers and PEPCK/G6Pase mRNA quantification

    PMID:11479628 PMID:11748271

    Open questions at the time
    • Receptor mediating hepatic action not identified
    • Did not connect to specific oligomeric form
  4. 2002 High

    Genetic loss-of-function placed adiponectin upstream of muscle FATP-1 expression and IRS-1/PI3-kinase insulin signaling, mechanistically linking it to insulin resistance.

    Evidence Adiponectin knockout mouse with viral rescue, muscle PI3-kinase activity assays, and myocyte treatment

    PMID:12068289

    Open questions at the time
    • Did not resolve receptor or intracellular adaptor
    • Relationship between TNF-α elevation and insulin resistance correlative
  5. 2002 High

    Demonstrated that oligomerization state — controlled by Cys-39 disulfide bonds — determines bioactivity and signaling pathway selection.

    Evidence Size-exclusion chromatography, Cys-39 mutagenesis, in vivo glucose assays, hepatocyte glucose output, and NF-κB reporter/IκB-α Western blots with size-fractionated preparations

    PMID:12087086 PMID:12496257

    Open questions at the time
    • Receptors for distinct oligomers not yet identified
    • Physiological determinants of oligomer distribution beyond sex unclear
  6. 2003 High

    Resolved that trimers selectively activate AMPK while hexamer/HMW forms selectively activate NF-κB, formalizing oligomer-specific pathway routing.

    Evidence Freeze-etch EM, Cys-22 mutagenesis, AMPK Thr172 phosphorylation in isolated muscle, and NF-κB reporter assays

    PMID:14522956

    Open questions at the time
    • Receptor coupling each oligomer to its pathway not defined
    • In vivo relevance of NF-κB branch unaddressed
  7. 2004 High

    Identified T-cadherin as an oligomer-selective receptor binding hexamer/HMW species, explaining how oligomeric state confers receptor specificity.

    Evidence Retroviral expression cloning, magnetic-bead panning, co-immunoprecipitation, and isoform-specific binding with cysteine mutants

    PMID:15210937

    Open questions at the time
    • Downstream signaling from T-cadherin not established
    • T-cadherin lacks intracellular domain, leaving transduction mechanism open
  8. 2006 High

    Identified APPL1 as the intracellular adaptor coupling AdipoR1 to metabolic effectors and insulin cross-talk, providing the missing intracellular link.

    Evidence Yeast two-hybrid, reciprocal Co-IP, gain/loss-of-function, and lipid oxidation, glucose uptake, and GLUT4 translocation assays

    PMID:16622416

    Open questions at the time
    • Structural basis of APPL1–AdipoR1 interaction not defined
    • Relationship to AMPK activation branch incompletely resolved
  9. 2010 High

    Showed AdipoR1 forms GxxxG-dependent homodimers that adiponectin disrupts, indicating ligand-regulated receptor oligomerization as a signaling event.

    Evidence BiFC, flow cytometry, GxxxG-motif mutagenesis, and endogenous AdipoR1 detection in human muscle

    PMID:20332107

    Open questions at the time
    • Functional consequence of dimer disruption for downstream signaling not quantified
    • Whether AdipoR2 behaves identically untested
  10. 2012 Medium

    Mechanistically tied muscle AdipoR1 signaling to AMPK/SIRT1/PGC-1α-driven mitochondrial biogenesis as the basis of insulin sensitization.

    Evidence Muscle-specific AdipoR1 knockout mice with mitochondrial biogenesis and pathway analyses

    PMID:22492282

    Open questions at the time
    • Conference-proceedings venue
    • Ca2+ and AMPK contributions not fully separated
  11. 2012 Medium

    Extended adiponectin's AMPK action beyond metabolism, showing it suppresses leptin-driven JAK/STAT3 signaling and MMP expression in cancer cells.

    Evidence Invasion assays, STAT3 phosphorylation/nuclear-translocation analysis, and pharmacological epistasis (AG490, Compound C)

    PMID:22327423

    Open questions at the time
    • Single cell line
    • Receptor mediating the anti-invasive effect not identified
  12. 2014 Medium

    Defined the upstream transcriptional regulation of adiponectin and the macrophage-state-dependence of its inflammatory output.

    Evidence Macrophage polarization with cytokine profiling and LXRα analysis; preadipocyte differentiation with pharmacological treatments (TNF-α, cAMP, ionomycin)

    PMID:11246823 PMID:25392268

    Open questions at the time
    • Direct transcription factors at the ADIPOQ promoter not fully mapped
    • In vivo relevance of macrophage polarization switch untested
  13. 2015 Medium

    Identified an osteocalcin–GPRC6A signaling cascade that induces adiponectin via PPARγ, linking bone-derived signals to adipokine expression.

    Evidence 3T3-L1 differentiation, pharmacological inhibitor dissection (U0126, PKA inhibitors), and in vivo oral GluOC administration

    PMID:25562427

    Open questions at the time
    • Single lab
    • Quantitative contribution to circulating adiponectin in vivo unclear
  14. 2021 High

    Bidirectional genetic manipulation established adiponectin as a direct regulator of healthspan and lifespan, not merely acute metabolism.

    Evidence Adiponectin knockout and transgenic overexpression mouse lifespan studies with metabolic and histological assessment

    PMID:33904399

    Open questions at the time
    • Molecular mediators of longevity effect not pinpointed
    • Whether oligomer- or receptor-specific signaling underlies the phenotype unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct oligomeric forms are coupled to specific receptors (AdipoR1/R2, T-cadherin) and intracellular adaptors to produce divergent metabolic, inflammatory, and longevity outcomes in vivo remains unresolved.
  • No unified structural model linking oligomer to receptor to pathway
  • T-cadherin transduction mechanism undefined
  • Mediators of lifespan extension unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0048018 receptor ligand activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005576 extracellular region 3 GO:0031012 extracellular matrix 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2
Partners
ADIPOR1APPL1CDH13

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 ADIPOQ (GBP28/apM1) was isolated from human plasma as a gelatin-binding protein. Structural analysis revealed it is encoded by the adipose-specific apM1 cDNA and contains a secretory signal sequence, collagen-like repeats, and a globular C-terminal domain, enabling homo-trimer formation and higher-order oligomeric complexes via its collagen-like domain. Affinity purification on gelatin-Cellulofine, N-terminal amino acid sequencing, protease peptide mapping, SDS-PAGE under reducing and non-reducing conditions, gel chromatography, cDNA sequence matching Journal of biochemistry High 8947845
2001 A single injection of recombinant Acrp30 in mice transiently lowered basal glucose levels and abolished hyperglycemia in ob/ob, NOD, and streptozotocin-treated mice independent of changes in insulin levels. In isolated hepatocytes, Acrp30 enhanced the ability of sub-physiological insulin to suppress glucose production, identifying the liver as a primary target organ. Intraperitoneal injection of purified recombinant protein in multiple mouse models; isolated hepatocyte glucose production assay Nature medicine High 11479628
2001 Acrp30 infusion during a pancreatic euglycemic clamp in conscious mice caused a ~65% reduction in endogenous glucose production and reduced hepatic gluconeogenic enzyme mRNAs (PEPCK and G6Pase) by >50%, without affecting peripheral glucose uptake, glycolysis, or glycogen synthesis, establishing hepatic gluconeogenesis suppression as the primary mechanism of Acrp30-mediated glucose lowering. Pancreatic euglycemic clamp with intravenous Acrp30 infusion; isotopic glucose flux measurements; hepatic enzyme mRNA quantification The Journal of clinical investigation High 11748271
2002 Adiponectin/ACRP30 knockout mice showed delayed clearance of plasma free fatty acids, reduced FATP-1 mRNA in muscle, elevated adipose TNF-alpha mRNA and plasma TNF-alpha, and severe diet-induced insulin resistance with reduced IRS-1-associated PI3-kinase activity in muscle. Viral re-expression of adiponectin reversed these defects, placing adiponectin upstream of FATP-1 expression and IRS-1-mediated insulin signaling in muscle. Gene knockout mouse model, viral-mediated gene rescue, muscle PI3-kinase activity assay, cultured myocyte TNF-alpha/adiponectin treatment Nature medicine High 12068289
2002 Acrp30 circulates as trimeric and high-molecular-weight (HMW) oligomeric complexes whose distribution shows sexual dimorphism (females have more HMW). Disulfide bonds via Cys-39 are required for HMW complex formation. Mutation of Cys-39 (C39S) produces trimers that are more bioactive than HMW forms in reducing serum glucose and suppressing hepatic glucose output in primary hepatocytes, demonstrating that oligomerization state regulates bioactivity. SDS-PAGE, size-exclusion chromatography, site-directed mutagenesis (Cys-39), DTT reduction, in vivo glucose assay, primary hepatocyte glucose output assay The Journal of biological chemistry High 12496257
2002 Hexameric and higher molecular weight (HMW) isoforms of Acrp30 activate NF-κB in C2C12 myocytes via phosphorylation and degradation of IκB-alpha, whereas trimeric Acrp30 and globular domain (gAcrp30) do not, establishing oligomerization-state-dependent NF-κB signaling. NF-κB reporter assay, Western blot for IκB-α phosphorylation/degradation, size-fractionated Acrp30 preparations from E. coli and HEK293T cells The Journal of biological chemistry High 12087086
2003 Trimeric Acrp30 (but not hexameric or HMW forms) activates AMP-activated protein kinase alpha (phosphorylation at Thr172) in isolated rat muscle. Conversely, HMW and hexameric Acrp30 activate NF-κB but trimers do not. Cys-22 disulfide bonds are required for hexamer/HMW formation but not trimer stability, establishing that different oligomeric forms activate distinct signaling pathways. Freeze-etch electron microscopy, site-directed mutagenesis (Cys22 to Ala), DTT reduction, AMPK phosphorylation assay in isolated muscle, NF-κB reporter assay The Journal of biological chemistry High 14522956
2004 T-cadherin was identified as a binding receptor for hexameric and HMW species of adiponectin, but not for trimeric or globular species. Binding requires eukaryotic post-translational modifications on adiponectin and the N-terminal cysteine required for hexamer/HMW formation; a C-terminal cysteine mutant that cannot form hexamers/HMW failed to bind T-cadherin in co-immunoprecipitation. Retroviral cDNA expression library screen, magnetic bead panning for adiponectin binding, co-immunoprecipitation, T-cadherin overexpression in Ba/F3 cells Proceedings of the National Academy of Sciences of the United States of America High 15210937
2006 APPL1 (adaptor protein with PTB, PH and leucine zipper domains) was identified as a direct binding partner of AdipoR1 intracellular domain by yeast two-hybrid. APPL1 interaction with adiponectin receptors in mammalian cells is stimulated by adiponectin. APPL1 overexpression increases, and APPL1 knockdown reduces, adiponectin-stimulated lipid oxidation, glucose uptake, and GLUT4 membrane translocation. Adiponectin also stimulates APPL1–Rab5 interaction, promoting GLUT4 translocation. APPL1 mediates cross-talk between adiponectin and insulin signaling pathways. Yeast two-hybrid screening, co-immunoprecipitation in mammalian cells, APPL1 overexpression/siRNA knockdown, lipid oxidation assay, glucose uptake assay, GLUT4 translocation assay Nature cell biology High 16622416
1999 The GBP28/ADIPOQ gene was mapped to human chromosome 3q27 by FISH and found to span 16 kb with 3 exons and 2 introns. The gene lacks a TATA box and its exon-intron organization resembles the leptin gene, providing structural basis for understanding its transcriptional regulation. Genomic cloning (lambda and BAC clones), FISH chromosomal mapping, sequence analysis of exon-intron boundaries Gene Medium 10095105
2001 GBP28/adiponectin expression is normally absent in mouse liver, but after CCl4-induced hepatic injury, circulating GBP28 binds to hepatocyte extracellular matrix early (3–6 h), and GBP28 mRNA is subsequently markedly induced in damaged hepatocytes. IL-6 treatment of human HepG2 hepatoma cells also induced GBP28 expression, identifying liver as a secondary production site regulated by injury and inflammatory signals. Immunohistochemistry, quantitative RT-PCR, in situ hybridization in CCl4-treated mouse liver; IL-6 treatment of HepG2 cells Biochemical and biophysical research communications Medium 11444852
2001 Mouse Acrp30 gene was mapped to the telomere of chromosome 16 (syntenic to human 3q27), and alternative polyadenylation produces two distinct mRNA species. Acrp30 expression is induced only at late stages of mouse embryonic development. The promoter was shown to drive strong adipocyte-specific expression in tissue culture cells. Chromosomal mapping, RT-PCR for alternative polyadenylation, developmental expression analysis, promoter-reporter assays in tissue culture Biochemical and biophysical research communications Medium 11162643
2010 AdipoR1 forms endogenous homodimers in multiple cell lines and human muscle tissue. A GxxxG motif in the fifth transmembrane domain is required for dimerization; mutation of both glycines (to Phe or Glu) disrupts dimerization. Adiponectin decreases AdipoR1 dimerization in a concentration-dependent manner, with this effect primarily mediated by the collagen-like domain of full-length adiponectin. Bimolecular fluorescence complementation (BiFC), flow cytometry, site-directed mutagenesis of GxxxG motif, Western blot of endogenous AdipoR1 in human muscle Journal of cell science High 20332107
2000 TNF-alpha reduces apM1 expression and secretion in differentiating primary human preadipocytes, while dibutyryl-cAMP also reduces expression. Ionomycin increases secretion of apM1. These findings establish transcriptional/secretory regulatory mechanisms for ADIPOQ in human adipocytes. Primary human preadipocyte differentiation culture, polyclonal antibody for apM1 detection, pharmacological treatments (ionomycin, db-cAMP, TNF-alpha), glycerol-3-phosphate dehydrogenase activity as differentiation marker Hormone and metabolic research Medium 11246823
2015 Uncarboxylated osteocalcin (GluOC) induces adiponectin expression in adipocytes via GPRC6A receptor activation → cAMP accumulation → PKA activation → Src → Rap1 → ERK → CREB phosphorylation → PPARγ upregulation → adiponectin expression. ERK inhibition (U0126) blocked CREB phosphorylation. In vivo, oral GluOC in mice increased PPARγ and adiponectin expression in gonadal white adipocytes. 3T3-L1 adipocyte differentiation assay, pharmacological inhibitors (U0126, PKA inhibitors), Western blot for signaling intermediates, in vivo mouse oral GluOC administration Cellular signalling Medium 25562427
2012 Adiponectin/AdipoR1 signaling in muscle regulates mitochondrial biogenesis via AMPK- and SIRT1-mediated PGC-1α activation and Ca2+-dependent upregulation of PGC-1α expression. Muscle-specific AdipoR1 knockout mice had impaired mitochondrial biogenesis and insulin resistance, revealing this as the mechanistic basis for adiponectin's insulin-sensitizing effect in muscle. Muscle-specific AdipoR1 knockout mouse, mitochondrial biogenesis assays, AMPK/SIRT1/PGC-1α pathway analysis Cold Spring Harbor symposia on quantitative biology Medium 22492282
2014 Macrophage polarization state controls AdipoR1/R2 expression and adiponectin signaling outcome: classical M1 activation suppresses AdipoR expression (40–60% reduction) and causes adiponectin to induce pro-inflammatory cytokines (TNF-α, IL-6, IL-12 >10-fold), whereas M2 activation preserves AdipoR expression and adiponectin induces anti-inflammatory IL-10. Adiponectin upregulates AdipoR mRNA and protein in macrophages via LXRα. Mouse bone marrow and peritoneal macrophage polarization, cytokine ELISA/multiplex, AdipoR mRNA/protein quantification, LXRα pathway analysis FASEB journal Medium 25392268
2012 Acrp30 inhibits leptin-induced invasion of SPEC-2 endometrial cancer cells by activating AMPK and thereby reducing STAT3 phosphorylation and nuclear translocation, with downstream reduction of MMP-2 and MMP-9. JAK/STAT3 inhibitor and AMPK inhibitor experiments confirmed the pathway: Acrp30 acts via AMPK to suppress the JAK/STAT3 axis activated by leptin. Matrigel transwell invasion assay, Western blot for STAT3 phosphorylation, cell immunofluorescence for STAT3 nuclear translocation, pharmacological inhibitors (AG490, Compound C, IL-6), qRT-PCR for MMP-2/MMP-9 Oncology reports Medium 22327423
2021 Adiponectin null mice display exacerbated age-related glucose and lipid metabolism disorders and shortened lifespan on both chow and high-fat diet. Transgenic mice with elevated circulating adiponectin have improved systemic insulin sensitivity, reduced age-related tissue inflammation and fibrosis, and prolonged healthspan and median lifespan, establishing adiponectin as a direct regulator of aging and longevity. Adiponectin knockout mouse aging study, adiponectin transgenic overexpression mouse, glucose/lipid metabolism assays, histological assessment of tissue inflammation and fibrosis, lifespan analysis eLife High 33904399

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. The Journal of clinical investigation 2177 16823476
2001 The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nature medicine 2036 11479628
2005 Adiponectin and adiponectin receptors. Endocrine reviews 1978 15897298
2002 Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nature medicine 1669 12068289
2002 ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends in endocrinology and metabolism: TEM 949 11854024
2002 Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications fpr metabolic regulation and bioactivity. The Journal of biological chemistry 875 12496257
2001 Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. The Journal of clinical investigation 719 11748271
1996 Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. Journal of biochemistry 698 8947845
2004 T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. Proceedings of the National Academy of Sciences of the United States of America 671 15210937
2003 Obesity, adiponectin and vascular inflammatory disease. Current opinion in lipidology 576 14624132
2006 APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function. Nature cell biology 551 16622416
2018 Adiponectin Regulation and Function. Comprehensive Physiology 485 29978896
2012 Role of leptin and adiponectin in insulin resistance. Clinica chimica acta; international journal of clinical chemistry 469 23266767
2003 Role of disulfide bonds in Acrp30/adiponectin structure and signaling specificity. Different oligomers activate different signal transduction pathways. The Journal of biological chemistry 392 14522956
2004 A family of Acrp30/adiponectin structural and functional paralogs. Proceedings of the National Academy of Sciences of the United States of America 359 15231994
2002 Oligomerization state-dependent activation of NF-kappa B signaling pathway by adipocyte complement-related protein of 30 kDa (Acrp30). The Journal of biological chemistry 307 12087086
2006 Adiponectin actions in the cardiovascular system. Cardiovascular research 257 17140553
2009 Adiponectin action from head to toe. Endocrine 248 20963555
2020 Adiponectin: Role in Physiology and Pathophysiology. International journal of preventive medicine 245 33088464
2012 Adiponectin receptor signalling in the brain. British journal of pharmacology 240 21718299
2008 APPL1: role in adiponectin signaling and beyond. American journal of physiology. Endocrinology and metabolism 235 18854421
2008 Protective vascular and myocardial effects of adiponectin. Nature clinical practice. Cardiovascular medicine 232 19029992
2007 The physiological and pathophysiological role of adiponectin and adiponectin receptors in the peripheral tissues and CNS. FEBS letters 210 18054335
2002 ACRP30, a new hormone controlling fat and glucose metabolism. European journal of pharmacology 203 12007537
2004 Adiponectin and atherosclerotic disease. Clinica chimica acta; international journal of clinical chemistry 180 15149866
2009 Adiponectin in health and disease: evaluation of adiponectin-targeted drug development strategies. Trends in pharmacological sciences 176 19359049
2006 Genetic architecture of the APM1 gene and its influence on adiponectin plasma levels and parameters of the metabolic syndrome in 1,727 healthy Caucasians. Diabetes 175 16443770
2009 Adiponectin and cardiovascular disease. Circulation journal : official journal of the Japanese Circulation Society 168 19261992
2008 Adiponectin: an update. Diabetes & metabolism 160 18069030
2000 Decreased expression of apM1 in omental and subcutaneous adipose tissue of humans with type 2 diabetes. International journal of experimental diabetes research 155 11469400
2000 Influences of ionomycin, dibutyryl-cycloAMP and tumour necrosis factor-alpha on intracellular amount and secretion of apM1 in differentiating primary human preadipocytes. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 150 11246823
2005 Expression of adiponectin and its receptors in swine. Journal of animal science 141 15705753
2006 ACDC/adiponectin polymorphisms are associated with severe childhood and adult obesity. Diabetes 130 16443793
2008 Expression of adiponectin and adiponectin receptors in human pituitary gland and brain. Neuroendocrinology 127 18698133
2013 Adiponectin as a routine clinical biomarker. Best practice & research. Clinical endocrinology & metabolism 120 24417951
2014 Adiponectin and energy homeostasis. Reviews in endocrine & metabolic disorders 118 24170312
2004 Single nucleotide polymorphisms in the proximal promoter region of the adiponectin (APM1) gene are associated with type 2 diabetes in Swedish caucasians. Diabetes 118 14749263
2014 Adiponectin signaling in the liver. Reviews in endocrine & metabolic disorders 114 24297186
2016 Unravelling the adiponectin paradox: novel roles of adiponectin in the regulation of cardiovascular disease. British journal of pharmacology 112 27629236
2020 Adiponectin and Cognitive Decline. International journal of molecular sciences 110 32188008
2005 Hypoadiponectinaemia and high risk of type 2 diabetes are associated with adiponectin-encoding (ACDC) gene promoter variants in morbid obesity: evidence for a role of ACDC in diabesity. Diabetologia 108 15830179
2005 Adiponectin, an adipocyte-derived protein. Physiological research 101 15544426
2001 Change in expression of GBP28/adiponectin in carbon tetrachloride-administrated mouse liver. Biochemical and biophysical research communications 100 11444852
2017 Adiponectin-Resistance in Obesity. Advances in experimental medicine and biology 99 28585210
1999 Organization of the gene for gelatin-binding protein (GBP28). Gene 98 10095105
2005 Linkage of plasma adiponectin levels to 3q27 explained by association with variation in the APM1 gene. Diabetes 97 15616038
2004 Adiponectin, obesity, and cardiovascular disease. Biochimie 95 15589686
2003 Dual roles of adiponectin/Acrp30 in vivo as an anti-diabetic and anti-atherogenic adipokine. Current drug targets. Immune, endocrine and metabolic disorders 94 14683455
2019 Mechanisms of Adiponectin Action: Implication of Adiponectin Receptor Agonism in Diabetic Kidney Disease. International journal of molecular sciences 87 30974901
2010 Molecular mechanisms of signal transduction via adiponectin and adiponectin receptors. Biological chemistry 85 20536390
2021 Adiponectin preserves metabolic fitness during aging. eLife 83 33904399
2015 Signaling pathway for adiponectin expression in adipocytes by osteocalcin. Cellular signalling 82 25562427
2014 Macrophage polarization phenotype regulates adiponectin receptor expression and adiponectin anti-inflammatory response. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 82 25392268
2015 Adiponectin/adiponectin receptor in disease and aging. NPJ aging and mechanisms of disease 75 28721260
2010 Adiponectin receptor binding proteins--recent advances in elucidating adiponectin signalling pathways. FEBS letters 74 20875820
2010 Adiponectin and adiponectin receptors in the mouse preimplantation embryo and uterus. Human reproduction (Oxford, England) 72 21106494
2009 Adiponectin, an unlocking adipocytokine. Cardiovascular therapeutics 72 19207481
2007 Adiponectin, the controversial hormone. Public health nutrition 69 17903323
2005 Common Polymorphisms in the Adiponectin Gene ACDC Are Not Associated With Diabetes in Pima Indians. Diabetes 69 15616040
2005 Adiponectin and human pregnancy. Current diabetes reports 65 16033679
2017 Cardiovascular Adiponectin Resistance: The Critical Role of Adiponectin Receptor Modification. Trends in endocrinology and metabolism: TEM 64 28473178
2006 Cartducin, a paralog of Acrp30/adiponectin, is induced during chondrogenic differentiation and promotes proliferation of chondrogenic precursors and chondrocytes. Journal of cellular physiology 64 16155912
2012 Adiponectin oligomerization state and adiponectin receptors airway expression in chronic obstructive pulmonary disease. The international journal of biochemistry & cell biology 63 22233975
2003 The genetics of adiponectin. Current diabetes reports 63 12728641
2001 Chromosomal localization, expression pattern, and promoter analysis of the mouse gene encoding adipocyte-specific secretory protein Acrp30. Biochemical and biophysical research communications 60 11162643
2013 GLP-1 analogue prevents NAFLD in ApoE KO mice with diet and Acrp30 knockdown by inhibiting c-JNK. Liver international : official journal of the International Association for the Study of the Liver 57 23432843
2022 Segmentation, tracking and cell cycle analysis of live-cell imaging data with Cell-ACDC. BMC biology 55 35932043
2007 Migraine and adiponectin: is there a connection? Cephalalgia : an international journal of headache 54 17448181
2023 Role of Leptin and Adiponectin in Carcinogenesis. Cancers 51 37686525
2006 Interactions between noncontiguous haplotypes in the adiponectin gene ACDC are associated with plasma adiponectin. Diabetes 51 16443790
2019 Pulmonary Hypertension and Obesity: Focus on Adiponectin. International journal of molecular sciences 50 30791536
2011 Polymorphisms of ADIPOQ and ADIPOR1 and prostate cancer risk. Metabolism: clinical and experimental 48 21397927
2016 Adiponectin and colorectal cancer. Surgery today 46 27061803
2016 Review: adiponectin in retinopathy. Biochimica et biophysica acta 46 27155572
2019 Potential Adiponectin Receptor Response Modifier Therapeutics. Frontiers in endocrinology 45 31456747
2013 Cardiometabolic effects of adiponectin. Best practice & research. Clinical endocrinology & metabolism 45 24417948
2017 Adiponectin promotes preadipocyte differentiation via the PPARγ pathway. Molecular medicine reports 44 29115433
2012 Acrp30 inhibits leptin-induced metastasis by downregulating the JAK/STAT3 pathway via AMPK activation in aggressive SPEC-2 endometrial cancer cells. Oncology reports 42 22327423
2012 Genetics of adiponectin. Biochimie 42 22449616
2005 ACDC/adiponectin and PPAR-gamma gene polymorphisms: implications for features of obesity. Obesity research 42 16421345
2012 Adiponectin in metabolic bone disease. Current medicinal chemistry 41 22876926
2007 Circulating adiponectin and adiponectin receptor expression in skeletal muscle: effects of exercise. Diabetes/metabolism research and reviews 41 17966120
2025 Adiponectin and Adiponectin Receptors in Atherosclerosis. Endocrine reviews 40 39106421
2014 Association of adiponectin gene (ADIPOQ) rs2241766 polymorphism with obesity in adults: a meta-analysis. PloS one 40 24740426
2010 Adiponectin and breast cancer. Medical oncology (Northwood, London, England) 40 20625941
2018 Adiponectin and adiponectin receptor 1 overexpression enhance inflammatory bowel disease. Journal of biomedical science 39 29540173
2012 Glucocorticoid effects on adiponectin expression. Vitamins and hormones 39 23017716
2018 Adiponectin as a novel biomarker for liver fibrosis. World journal of hepatology 38 30386464
2013 Adiponectin effects on the kidney. Best practice & research. Clinical endocrinology & metabolism 38 24417947
2010 Dimerization of adiponectin receptor 1 is inhibited by adiponectin. Journal of cell science 37 20332107
2007 Adiponectin, obesity and atherosclerosis. Scandinavian journal of clinical and laboratory investigation 37 17763181
2001 Characterization of mouse GBP28 and its induction by exposure to cold. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 37 11244461
2013 Adiponectin modulates NK-cell function. European journal of immunology 36 23401034
2022 Targeting Adiponectin in Breast Cancer. Biomedicines 35 36428526
2007 Adiponectin and adiponectin receptors in obesity-linked insulin resistance. Novartis Foundation symposium 35 18269182
2024 Adiponectin Resistance in Obesity: Adiponectin Leptin/Insulin Interaction. Advances in experimental medicine and biology 33 39287861
2014 Association of ADIPOQ polymorphisms with obesity risk: a meta-analysis. Human immunology 33 25223469
2021 An Explanation for the Adiponectin Paradox. Pharmaceuticals (Basel, Switzerland) 31 34959666
2015 Adiponectin in asthma: implications for phenotyping. Current protein & peptide science 31 25760347
2012 Adiponectin, adiponectin receptors, and epigenetic regulation of adipogenesis. Cold Spring Harbor symposia on quantitative biology 31 22492282

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