Affinage

ADIPOQ

Adiponectin · UniProt Q15848

Round 2 corrected
Length
244 aa
Mass
26.4 kDa
Annotated
2026-04-28
130 papers in source corpus 34 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Adiponectin (ADIPOQ) is an abundant adipocyte-derived secreted hormone that circulates as disulfide-linked trimers, hexamers, and high-molecular-weight (HMW) multimers, each oligomeric species activating distinct signaling cascades: trimers preferentially stimulate AMPK in skeletal muscle to increase fatty-acid oxidation and glucose uptake, while HMW/hexameric forms act on the liver to suppress gluconeogenesis (PEPCK, G6Pase) and activate NF-κB in myocytes (PMID:12368907, PMID:14699128, PMID:14522956). Adiponectin signals through the seven-transmembrane receptors AdipoR1 (muscle) and AdipoR2 (liver), scaffolded by caveolin-3 and the adaptor APPL1, to activate AMPK→ACC, AMPK→Akt→eNOS (NO production), and cAMP/PKA pathways, thereby exerting insulin-sensitizing, anti-inflammatory, and vasoprotective effects (PMID:12802337, PMID:18854421, PMID:22328772, PMID:12944390). In the vasculature, adiponectin suppresses TNF-α-induced endothelial adhesion molecule expression via cAMP/PKA-dependent inhibition of NF-κB, reduces macrophage scavenger receptor expression to prevent foam-cell formation, and induces anti-inflammatory cytokines IL-10 and IL-1RA in monocytes/macrophages (PMID:10982546, PMID:11222466, PMID:15369797). Bidirectional genetic models demonstrate that adiponectin deficiency causes diet-induced insulin resistance and shortened lifespan, while overexpression extends healthspan by reducing systemic inflammation and tissue fibrosis (PMID:12068289, PMID:33904399).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1995 High

    Identification of Acrp30/adiponectin as a novel adipocyte-exclusive secreted protein that forms oligomers and is insulin-regulated established the existence of a major adipokine, opening the question of its physiological function.

    Evidence Differential display cloning, Western blot, oligomer characterization, and insulin stimulation in 3T3-L1 adipocytes

    PMID:7592907

    Open questions at the time
    • Biological function unknown
    • Receptor(s) unidentified
    • Relevance of oligomeric forms unclear
  2. 1996 High

    Cloning of the full-length cDNA and demonstration that adiponectin expression is reduced in obesity linked the protein to metabolic disease and defined its domain architecture (signal peptide, collagenous domain, C1q-like globular domain).

    Evidence mRNA differential display, cDNA cloning, Northern blot in obese vs. lean mice and humans; biochemical purification from human plasma confirming disulfide-linked ~420 kDa oligomers

    PMID:8631877 PMID:8947845

    Open questions at the time
    • Mechanism of obesity-associated downregulation unknown
    • No receptor identified
    • Whether oligomerization is functionally important untested
  3. 1999 High

    Demonstration that adiponectin resides in a PI3K-dependent regulated secretory compartment distinct from GLUT4 vesicles revealed that adipocytes actively control adiponectin release; concurrent discovery that adiponectin inhibits TNF-α-induced endothelial adhesion molecules established its anti-inflammatory vascular role.

    Evidence Deconvolution microscopy and PI3K inhibitors in 3T3-L1 adipocytes; cell ELISA and monocyte adhesion assay in HAECs

    PMID:10444069 PMID:10604883

    Open questions at the time
    • Downstream endothelial signaling pathway unknown
    • Secretory compartment identity (recycling endosome vs. other) undefined
  4. 2000 High

    Elucidation of the cAMP/PKA-dependent mechanism by which adiponectin suppresses NF-κB (IκB-α phosphorylation) in endothelial cells, and of its ability to reduce macrophage foam-cell formation by downregulating class A scavenger receptor transcription, established the molecular basis for its anti-atherogenic activity.

    Evidence EMSA, IκB-α immunoblot, adenylate cyclase/PKA inhibitors in HAECs; scavenger receptor promoter reporter assay, Oil Red O staining, and C1qRp blockade in macrophages

    PMID:10961870 PMID:10982546 PMID:11222466

    Open questions at the time
    • Identity of the endothelial receptor unknown
    • Whether C1qRp is a bona fide signaling receptor or merely a binding partner unresolved
  5. 2001 High

    In vivo studies showed adiponectin suppresses hepatic glucose production (reducing PEPCK and G6Pase) and reverses insulin resistance in obese and lipoatrophic mice by decreasing tissue triglyceride content, establishing the liver and muscle as primary metabolic target organs.

    Evidence Recombinant adiponectin injection in ob/ob, NOD, and STZ mice; euglycemic clamp; isolated hepatocyte glucose output; triglyceride content assays in muscle/liver

    PMID:11479627 PMID:11479628 PMID:11748271

    Open questions at the time
    • Downstream kinase mediating hepatic effects unknown
    • Receptor identity still missing
  6. 2002 High

    AMPK was identified as the central kinase mediating adiponectin's metabolic effects — phosphorylating ACC to increase fatty-acid oxidation and glucose uptake — with dominant-negative AMPK blocking all effects; concurrently, adiponectin-knockout mice confirmed in vivo necessity for insulin sensitivity, and structure–function studies showed Cys-39-dependent disulfide bonds govern oligomer assembly and differential bioactivity of trimers vs. HMW forms.

    Evidence Dominant-negative AMPK in myocytes/hepatocytes; AMPK/ACC phosphorylation assays; adiponectin-KO mice with viral rescue; Cys-39 mutagenesis with in vivo glucose and hepatocyte glucose output assays; NF-κB reporter with purified oligomeric fractions

    PMID:12068289 PMID:12087086 PMID:12368907 PMID:12496257

    Open questions at the time
    • Receptor still unidentified
    • How different oligomers are directed to different receptors unknown
    • Intracellular adaptor proteins linking receptor to AMPK not discovered
  7. 2003 High

    Expression cloning identified AdipoR1 and AdipoR2 as seven-transmembrane adiponectin receptors mediating AMPK and PPARα activation; T-cadherin was later found as a receptor for hexameric/HMW forms; the AMPK→Akt→eNOS cascade was defined as the mechanism for adiponectin-stimulated NO production and angiogenesis; and PPARγ/RXR binding to a PPRE in the ADIPOQ promoter established the transcriptional regulation of adiponectin itself.

    Evidence Expression cloning with siRNA in C2C12 cells; dominant-negative AMPK/Akt epistasis in endothelial cells; EMSA and promoter mutagenesis in adipocytes; retroviral library screen for T-cadherin

    PMID:12802337 PMID:12829629 PMID:12944390 PMID:14522956 PMID:15210937

    Open questions at the time
    • T-cadherin lacks an intracellular domain — signaling mechanism downstream of T-cadherin unknown
    • Relative contributions of AdipoR1 vs. AdipoR2 to each tissue response not fully delineated
  8. 2006 Medium

    Routing of adiponectin secretion through Rab11-positive recycling endosomes (with Arf6 contribution) and v-SNARE Vti1a defined the intracellular trafficking pathway controlling adiponectin release from adipocytes.

    Evidence Dominant-negative Rab11, endosome ablation, and Brefeldin A in 3T3-L1 adipocytes; siRNA knockdown of Vti1a with secretion and glucose uptake assays

    PMID:16131485 PMID:16516854

    Open questions at the time
    • Dominant-negative Rab11 approach not validated by knockout or rescue
    • Whether Vti1a acts on the same or parallel pathway as Rab11 unclear
    • Molecular machinery sorting adiponectin into recycling endosomes not identified
  9. 2008 High

    Identification of APPL1 as a direct adaptor bridging AdipoR1/R2 intracellular domains to AMPK activation and insulin sensitization resolved how receptor engagement couples to downstream kinase cascades.

    Evidence Co-immunoprecipitation, PTB domain binding, APPL1 knockdown/overexpression with AMPK activity and glucose uptake readouts in skeletal muscle and endothelial cells

    PMID:18854421

    Open questions at the time
    • Whether APPL1 is the sole or one of multiple adaptors unknown
    • Crystal structure of AdipoR–APPL1 complex not resolved
  10. 2012 High

    Caveolin-3 was shown to scaffold the AdipoR1–APPL1–adenylate cyclase complex, enabling both AMPK-dependent and AMPK-independent (PKA) cardioprotective signaling, thereby adding a membrane microdomain requirement to the adiponectin signaling model.

    Evidence Co-IP and Cav-3 knockout mice with ischemia/reperfusion injury, infarct size measurement, PKA inhibitor studies

    PMID:22328772

    Open questions at the time
    • Whether Cav-3 scaffolding applies to non-cardiac tissues (e.g. skeletal muscle, endothelium) not tested
    • Role of lipid raft disruption vs. Cav-3 protein specifically not distinguished
  11. 2015 High

    Osteocalcin was identified as an upstream inducer of adiponectin transcription via GPRC6A→cAMP→PKA→ERK→CREB→PPARγ, establishing a bone–adipose endocrine axis; separately, adiponectin was shown to protect dystrophic muscle through AdipoR1–AMPK–SIRT1–PGC-1α signaling.

    Evidence Pharmacological pathway dissection with U0126 and PPARγ reporter in adipocytes; mdx × adiponectin-transgenic mice with force measurement and Evans Blue Dye assay

    PMID:25562427 PMID:26257862

    Open questions at the time
    • Whether osteocalcin–adiponectin axis is quantitatively relevant in humans unknown
    • Whether SIRT1–PGC-1α axis is engaged in non-dystrophic muscle contexts unclear
  12. 2021 High

    Bidirectional genetic models (knockout and transgenic overexpression) demonstrated that adiponectin is necessary and sufficient for metabolic healthspan: deficiency shortens lifespan with accelerated inflammation and fibrosis, while elevation extends median lifespan.

    Evidence Adiponectin-KO and adiponectin-overexpressing mice on chow and HFD, glucose/lipid tolerance, tissue fibrosis quantification, lifespan analysis

    PMID:33904399

    Open questions at the time
    • Specific tissue(s) responsible for lifespan extension not identified
    • Whether chronic adiponectin elevation has detrimental effects in other contexts (e.g. cancer) not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How T-cadherin, which lacks an intracellular domain, transduces hexameric/HMW adiponectin signals remains mechanistically unresolved; the structural basis of oligomer-specific receptor selectivity and the full spectrum of tissue-specific adaptor complexes downstream of AdipoR1/R2 are also unknown.
  • T-cadherin signaling mechanism completely undefined
  • No crystal structure of full-length AdipoR–adiponectin complex
  • Relative in vivo contributions of AdipoR1, AdipoR2, and T-cadherin to specific metabolic outcomes not genetically dissected in parallel

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5 GO:0098772 molecular function regulator activity 4
Localization
GO:0005576 extracellular region 3 GO:0031410 cytoplasmic vesicle 2 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-168256 Immune System 5 R-HSA-1430728 Metabolism 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-382551 Transport of small molecules 2
Partners
ADIPOR1ADIPOR2APPL1CAV3CDH13VTI1A

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Acrp30 (ADIPOQ) is a novel 30-kDa secretory protein made exclusively in adipocytes, forming large homo-oligomers that undergo post-translational modifications; its secretion is enhanced by insulin, identifying it as an abundant serum protein with structural similarity to complement factor C1q. Differential display cloning, Western blot, oligomer characterization, insulin stimulation assay in adipocytes The Journal of biological chemistry High 7592907
1996 AdipoQ encodes a 247-amino-acid secreted protein with a signal sequence, collagenous (Gly-X-Y) region, and a C1q-like globular domain; expression is adipose-specific and restricted to mature adipocytes, and is significantly reduced in obese mice and humans. mRNA differential display, cDNA cloning, Northern blot, in situ hybridization The Journal of biological chemistry High 8631877
1996 GBP28 (ADIPOQ) is a gelatin-binding plasma protein purified from human plasma; on SDS-PAGE it migrates as 28 kDa (reducing) or 68 kDa (non-reducing), and by gel chromatography as ~420 kDa, indicating disulfide-linked oligomeric complexes. Affinity chromatography (gelatin-Cellulofine), gel filtration, SDS-PAGE, N-terminal sequencing Journal of biochemistry High 8947845
1999 ADIPOQ (adiponectin) in 3T3-L1 adipocytes is stored in a regulated secretory compartment distinct from GLUT4 vesicles; insulin-stimulated secretion of ACRP30 requires phosphatidylinositol-3-kinase activity, and ACRP30 and GLUT4 occupy non-overlapping intracellular compartments. Deconvolution immunofluorescence microscopy, PI3K inhibitor (wortmannin/LY294002) treatment, insulin stimulation, secretion assay The Journal of cell biology High 10444069
1999 Adiponectin inhibits TNF-α-induced expression of endothelial adhesion molecules (VCAM-1, E-selectin, ICAM-1) and monocyte adhesion to human aortic endothelial cells at physiological concentrations. Cell ELISA, adhesion assay with THP-1 cells, treatment of HAECs with recombinant adiponectin Circulation High 10604883
2000 Adiponectin inhibits TNF-α-induced NF-κB activation in endothelial cells by suppressing IκB-α phosphorylation through a cAMP/PKA-dependent pathway; it specifically binds HAECs in a saturable manner without affecting TNF-α receptor interaction. Cell ELISA with biotinylated adiponectin, EMSA (NF-κB binding), immunoblotting (IκB-α phosphorylation), adenylate cyclase and PKA inhibitors, cAMP measurement Circulation High 10982546
2000 Adiponectin suppresses macrophage-to-foam cell transformation by reducing class A scavenger receptor (MSR) expression at mRNA and protein levels via decreased MSR promoter activity, without affecting CD36 expression; it also inhibits macrophage phagocytosis via the complement receptor C1qRp. Cholesteryl ester assay, Oil Red O staining, Northern blot, immunoblot, luciferase reporter assay, flow cytometry, anti-C1qRp antibody blockade Circulation High 11222466
2000 Adiponectin suppresses growth of myelomonocytic progenitors and induces apoptosis (subdiploid peaks, oligonucleosomal DNA fragmentation) in acute myelomonocytic leukemia lines; it also suppresses macrophage phagocytosis and LPS-induced TNF-α production, partly via the C1q receptor C1qRp. Colony formation assay, flow cytometry (sub-G1), DNA fragmentation assay, anti-C1qRp antibody blockade, TNF-α ELISA Blood High 10961870
2001 A single injection of recombinant Acrp30 in mice causes a 2–3-fold elevation in circulating levels and transiently lowers basal glucose; in isolated hepatocytes, Acrp30 enhances sub-physiological insulin-mediated suppression of glucose production, identifying the liver as a primary target organ. Recombinant protein injection in mice (ob/ob, NOD, STZ-treated), isolated hepatocyte glucose production assay Nature medicine High 11479628
2001 Adiponectin reverses insulin resistance in both obese and lipoatrophic mouse models by decreasing triglyceride content in muscle and liver through increased expression of fatty-acid combustion and energy dissipation molecules; combination of adiponectin and leptin fully reverses lipoatrophic insulin resistance. Recombinant adiponectin administration, triglyceride content assay in muscle/liver, gene expression profiling, adiponectin+leptin co-treatment in lipoatrophic mice Nature medicine High 11479627
2001 Intraperitoneal Acrp30 infusion during a euglycemic clamp reduces hepatic glucose production by 65% and decreases expression of gluconeogenic enzymes PEPCK and G6Pase by >50%, without affecting peripheral glucose uptake or glycolysis. Pancreatic euglycemic clamp in conscious mice, glucose flux measurement, hepatic mRNA analysis (PEPCK, G6Pase) The Journal of clinical investigation High 11748271
2002 Adiponectin activates AMP-activated protein kinase (AMPK) in skeletal muscle (both globular and full-length forms) and liver (full-length only), leading to phosphorylation of ACC, increased fatty-acid oxidation and glucose uptake; dominant-negative AMPK blocks all these effects. AMPK phosphorylation assay, ACC phosphorylation, fatty-acid oxidation assay, glucose uptake assay, dominant-negative AMPK mutant transfection in myocytes and hepatocytes Nature medicine High 12368907
2002 Adiponectin-knockout mice show severe diet-induced insulin resistance with reduced IRS-1-associated PI3-kinase activity in muscle, elevated TNF-α in adipose tissue, delayed FFA clearance, and reduced muscle FATP-1 mRNA; viral re-expression of adiponectin reverses these defects. Gene knockout, PI3K activity assay, TNF-α mRNA measurement, FATP-1 mRNA, FFA clearance, viral rescue experiment in KO mice Nature medicine High 12068289
2002 Acrp30 oligomer formation critically depends on disulfide bond formation via Cys-39; mutation of Cys-39 results in trimers that are more bioactive than higher-order oligomers with respect to lowering serum glucose and reducing hepatocyte glucose output; females display higher HMW complex levels than males. Mutagenesis (Cys-39 to Ser), DTT reduction, in vivo glucose measurement, primary hepatocyte glucose output assay, non-denaturing SDS-PAGE The Journal of biological chemistry High 12496257
2002 Only hexameric and higher-MW forms of Acrp30 activate NF-κB (via IκB-α phosphorylation/degradation) in C2C12 myocytes; trimeric Acrp30 does not activate NF-κB, demonstrating oligomerization state-dependent signaling specificity. NF-κB reporter assay, IκB-α phosphorylation by immunoblot, purified trimers and hexamers from E. coli and 293T cells The Journal of biological chemistry High 12087086
2003 Cloning of AdipoR1 (abundant in skeletal muscle) and AdipoR2 (predominant in liver) by expression cloning; both receptors have seven transmembrane domains but are structurally and functionally distinct from GPCRs; they mediate globular and full-length adiponectin binding and downstream AMPK and PPARα activation, fatty-acid oxidation, and glucose uptake. Expression cloning from C2C12 cDNA library, siRNA knockdown, AMPK/PPARα activity assays, fatty-acid oxidation, glucose uptake Nature High 12802337
2003 Trimeric and HMW/hexameric Acrp30 activate distinct signal transduction pathways: trimers activate AMPK (Thr172 phosphorylation) in muscle; HMW and hexamers activate NF-κB in C2C12 cells; Cys-22 disulfide bonds are required for hexamer and HMW assembly but not trimer stability. Freeze-etch electron microscopy, DTT reduction, Cys22Ala mutagenesis, AMPK phosphorylation assay (rat EDL muscle), NF-κB reporter assay The Journal of biological chemistry High 14522956
2003 The ratio of HMW to LMW adiponectin (S_A index), not absolute total adiponectin, correlates with insulin sensitivity; HMW adiponectin complex is the active form in vivo (dose-dependently lowers serum glucose), primarily acting on hepatic insulin sensitivity. Non-denaturing SDS-PAGE oligomer separation, euglycemic clamp, in vivo glucose infusion with defined oligomeric fractions in db/db mice and human cohorts The Journal of biological chemistry High 14699128
2003 Adiponectin stimulates NO production in vascular endothelial cells via a PI3K-dependent pathway involving phosphorylation of Akt (Ser473) and eNOS (Ser1179) by AMPK; dominant-negative AMPK (but not dominant-negative Akt) inhibits adiponectin-induced eNOS phosphorylation and NO production. DAF-2 DA fluorescent NO assay, phospho-specific immunoblotting, wortmannin inhibition, dominant-negative AMPK and Akt transfection in bovine aortic endothelial cells The Journal of biological chemistry High 12944390
2003 Adiponectin mutations G84R and G90S (associated with diabetes) fail to form HMW multimers; R112C and I164T mutants fail to assemble into trimers and show impaired secretion; an N-terminal Cys-to-Ser mutation abolishing multimers >trimers abrogates AMPK pathway activation in hepatocytes. Non-reducing/non-heat-denaturing SDS-PAGE, site-directed mutagenesis, transfection in NIH-3T3 cells, AMPK pathway assay in hepatocytes The Journal of biological chemistry High 12878598
2003 Adiponectin stimulates angiogenesis in vitro (HUVEC capillary differentiation and migration) and in vivo (Matrigel plug and corneal models) via cross-talk between AMPK and Akt signaling, both required for eNOS phosphorylation; dominant-negative AMPK blocks adiponectin-induced Akt phosphorylation, placing AMPK upstream of Akt. HUVEC tube formation, migration assay, dominant-negative AMPK and Akt transfection, phospho-immunoblotting, in vivo Matrigel and corneal angiogenesis assays The Journal of biological chemistry High 14557259
2003 PPARγ/RXR heterodimer directly binds a functional PPAR-responsive element (PPRE) in the human adiponectin promoter to drive transcription; LRH-1 binds a separate responsive element and augments PPARγ-induced transactivation; point mutations in either element markedly reduce basal and TZD-induced adiponectin promoter activity. Promoter deletion/mutation analysis, luciferase reporter assay, EMSA (direct binding), TZD treatment of 3T3-L1 and rat adipocytes Diabetes High 12829629
2003 Adiponectin induces anti-inflammatory cytokines IL-10 and IL-1RA and suppresses IFN-γ production in primary human monocytes, macrophages, and dendritic cells; adiponectin-treated macrophages show reduced phagocytotic and allo-stimulatory capacity. Primary human monocyte/macrophage/DC culture, cytokine ELISA, phagocytosis assay, mixed lymphocyte reaction Biochemical and biophysical research communications High 15369797
2004 T-cadherin (a GPI-anchored extracellular protein expressed on endothelial and smooth muscle cells) acts as a receptor specifically for hexameric and HMW forms of adiponectin (not trimer or globular forms); binding requires eukaryotic post-translational modifications of adiponectin and the N-terminal cysteine required for hexamer/HMW formation. Retroviral cDNA expression library screening on adiponectin-coated magnetic beads in Ba/F3 cells, co-immunoprecipitation, binding assays with oligomeric fractions, Cys-mutant adiponectin Proceedings of the National Academy of Sciences of the United States of America High 15210937
2004 Adiponectin induces endothelial cell apoptosis (caspase-8, -9, -3 cascade activation) as a mechanism of anti-angiogenesis; in a mouse tumor model, adiponectin inhibits primary tumor growth by reducing neovascularization and increasing tumor cell apoptosis. Endothelial cell proliferation/migration assay, chick CAM assay, mouse corneal angiogenesis, caspase activation assays, mouse tumor model with neovascularization quantification Proceedings of the National Academy of Sciences of the United States of America High 14983034
2005 The v-SNARE Vti1a is a component of insulin-sensitive GLUT4-containing vesicles in adipocytes; siRNA-mediated depletion of Vti1a significantly inhibits both adiponectin (ACRP30) secretion and insulin-stimulated glucose uptake, indicating Vti1a regulates a step common to GLUT4 and ACRP30 trafficking. Proteomics (mass spectrometry) of purified GLUT4 membranes, siRNA knockdown, adiponectin secretion assay, deoxyglucose uptake assay in 3T3-L1 adipocytes The Journal of biological chemistry High 16131485
2006 ACRP30 secretion from 3T3-L1 adipocytes is routed through Rab11-positive recycling endosomes; dominant-negative Rab11-S25N and endosome ablation reduce basal and insulin-stimulated ACRP30 secretion; Arf6 also contributes to this secretory pathway. Dominant-negative Rab11 overexpression, endosome ablation, Brefeldin A treatment, co-localization with transferrin receptor (endosomal marker), secretion assay in 3T3-L1 adipocytes Biochemical and biophysical research communications Medium 16516854
2008 APPL1, an adaptor protein with PTB domain, directly interacts with the intracellular regions of AdipoR1 and AdipoR2 and mediates adiponectin signaling, including AMPK activation and insulin sensitization in skeletal muscle; APPL1 is also required for adiponectin's anti-inflammatory and cytoprotective effects in endothelial cells. Co-immunoprecipitation, PTB domain binding assay, AMPK activity assay, glucose uptake in skeletal muscle, endothelial cell survival assay with APPL1 knockdown/overexpression American journal of physiology. Endocrinology and metabolism High 18854421
2009 Niacin stimulates adiponectin secretion through the GPR109A receptor via a pertussis toxin-sensitive (Gi) pathway; GPR109A knockout mice fail to increase adiponectin in response to niacin, and the effect is mimicked by β-hydroxybutyrate (endogenous GPR109A ligand) in primary adipocytes. In vivo niacin administration in rats and GPR109A-KO mice, primary adipocyte stimulation with pertussis toxin pretreatment, adiponectin ELISA, 3T3-L1 cell controls (low GPR109A expression) American journal of physiology. Endocrinology and metabolism High 19141678
2010 AdipoR1 forms homodimers via a GxxxG motif in the fifth transmembrane domain; mutation of both glycines (to Phe or Glu) modulates dimerization; adiponectin decreases AdipoR1 dimerization in a concentration-dependent manner, primarily through its collagen-like domain. Bimolecular fluorescence complementation (BiFC), flow cytometry, GxxxG mutagenesis, endogenous AdipoR1 dimer detection in cell lines and human muscle tissue Journal of cell science High 20332107
2012 Caveolin-3 is required for AdipoR1/Cav-3 complex formation via Cav-3 scaffolding domain motifs; AdipoR1/Cav-3 interaction is necessary for adiponectin-initiated AMPK-dependent and AMPK-independent (adenylate cyclase/PKA) cardioprotective signaling; APPL1 and adenylate cyclase form a complex with AdipoR1 in a Cav-3-dependent fashion. Co-immunoprecipitation, Cav-3 knockout mice (ischemia/reperfusion injury), infarct size measurement, AMPK activity assay, PKA inhibitor studies Arteriosclerosis, thrombosis, and vascular biology High 22328772
2015 Osteocalcin (GluOC) induces adiponectin expression in adipocytes via GPRC6A receptor → cAMP → PKA → Src → Rap1 → ERK → CREB → PPARγ → adiponectin; U0126 (ERK inhibitor) and GPRC6A blockade attenuate CREB phosphorylation and adiponectin induction. Intracellular cAMP measurement, PKA activity, phospho-ERK/CREB immunoblot, U0126 inhibition, PPARγ luciferase reporter, intermittent GluOC oral administration in mice Cellular signalling High 25562427
2015 Adiponectin protects mdx (Duchenne muscular dystrophy) mice via AdipoR1 and the AMPK-SIRT1-PGC-1α pathway, reducing NF-κB activation and inflammatory genes while upregulating utrophin A; adiponectin null mice have markedly reduced circulating adiponectin in the dystrophic context. mdx × adiponectin-transgenic cross, in vivo force measurement, Evans Blue Dye muscle damage assay, AMPK/SIRT1/PGC-1α immunoblot, NF-κB reporter, human myotube culture Skeletal muscle High 26257862
2021 Adiponectin null mice display exacerbated age-related glucose and lipid metabolism disorders and significantly shortened lifespan; transgenic mice with elevated circulating adiponectin show improved systemic insulin sensitivity, reduced age-related tissue inflammation and fibrosis, and prolonged healthspan and median lifespan. Adiponectin knockout and transgenic overexpression mouse models, glucose/lipid tolerance tests, tissue fibrosis quantification, lifespan analysis on chow and HFD eLife High 33904399

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nature medicine 3832 11479627
2002 Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nature medicine 3297 12368907
1995 A novel serum protein similar to C1q, produced exclusively in adipocytes. The Journal of biological chemistry 2549 7592907
2003 Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2514 12802337
2001 The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nature medicine 2034 11479628
2005 Adiponectin and adiponectin receptors. Endocrine reviews 1966 15897298
1999 Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 1753 10604883
1996 AdipoQ is a novel adipose-specific gene dysregulated in obesity. The Journal of biological chemistry 1746 8631877
2002 Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nature medicine 1667 12068289
1996 cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochemical and biophysical research communications 1642 8619847
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2000 Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation 1412 10982546
2001 Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 1044 11222466
2000 Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 1013 10961870
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2003 Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. The Journal of biological chemistry 956 14699128
2002 ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends in endocrinology and metabolism: TEM 947 11854024
2003 Adiponectin and metabolic syndrome. Arteriosclerosis, thrombosis, and vascular biology 879 14551151
2002 Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications fpr metabolic regulation and bioactivity. The Journal of biological chemistry 872 12496257
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2017 Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction. International journal of molecular sciences 849 28635626
2003 Adiponectin stimulates production of nitric oxide in vascular endothelial cells. The Journal of biological chemistry 833 12944390
2003 Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. The Journal of biological chemistry 821 12878598
2003 The role of the novel adipocyte-derived hormone adiponectin in human disease. European journal of endocrinology 816 12611609
2004 Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology (Baltimore, Md.) 782 15239085
2001 Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. The Journal of clinical investigation 718 11748271
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
1996 Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. Journal of biochemistry 698 8947845
2003 Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. Diabetes 673 12829646
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 670 15210937
2004 The human plasma proteome: a nonredundant list developed by combination of four separate sources. Molecular & cellular proteomics : MCP 658 14718574
2003 Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. The Journal of biological chemistry 642 14557259
2004 Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. Biochemical and biophysical research communications 640 15369797
2003 Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors. Diabetes 621 12829629
2004 Adiponectin as a biomarker of the metabolic syndrome. Circulation journal : official journal of the Japanese Circulation Society 589 15502375
2004 Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proceedings of the National Academy of Sciences of the United States of America 579 14983034
2003 Obesity, adiponectin and vascular inflammatory disease. Current opinion in lipidology 576 14624132
2002 Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes 574 11812766
2003 Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. American journal of physiology. Endocrinology and metabolism 566 12736161
2018 Adiponectin Regulation and Function. Comprehensive Physiology 481 29978896
2012 Role of leptin and adiponectin in insulin resistance. Clinica chimica acta; international journal of clinical chemistry 465 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 391 14522956
2004 A family of Acrp30/adiponectin structural and functional paralogs. Proceedings of the National Academy of Sciences of the United States of America 357 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
2020 Adiponectin: Role in Physiology and Pathophysiology. International journal of preventive medicine 242 33088464
2008 APPL1: role in adiponectin signaling and beyond. American journal of physiology. Endocrinology and metabolism 234 18854421
2008 Protective vascular and myocardial effects of adiponectin. Nature clinical practice. Cardiovascular medicine 231 19029992
2002 ACRP30, a new hormone controlling fat and glucose metabolism. European journal of pharmacology 203 12007537
2006 Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines. Diabetologia 188 16570162
2009 Adiponectin in health and disease: evaluation of adiponectin-targeted drug development strategies. Trends in pharmacological sciences 176 19359049
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
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