Affinage

ADIPOR1

Adiponectin receptor protein 1 · UniProt Q96A54

Length
375 aa
Mass
42.6 kDa
Annotated
2026-06-09
100 papers in source corpus 34 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/9 claims corpus-supported (89%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADIPOR1 is a seven-transmembrane adiponectin receptor that transduces adiponectin signals into metabolic, anti-inflammatory, and cytoprotective responses across many tissues, and additionally functions as an intrinsic ceramidase critical for membrane lipid homeostasis (PMID:17268472, PMID:35015730, PMID:30890562). Genetic disruption establishes ADIPOR1 as required for adiponectin-induced AMPK activation in vivo (PMID:17268472); in muscle it mediates extracellular Ca2+ influx that drives a CaMKKβ/AMPK/SIRT1/PGC-1α cascade to increase mitochondrial content (PMID:20357764), and in liver it acts upstream of LKB1/AMPK to suppress SREBP1c (PMID:19254698). Across cell types ADIPOR1 couples through the adaptor APPL1 and converges on AMPK/NF-κB to deliver anti-apoptotic and anti-inflammatory effects (PMID:21552570, PMID:29486166, PMID:25099270). ADIPOR1 binds the ER/plasma-membrane protein ERp46 via its cytoplasmic N-terminal residues (1–70), which sets receptor surface levels and biases downstream AMPK versus p38MAPK signaling (PMID:20074551). Independently of adiponectin, ADIPOR1 sustains fatty-acid desaturase expression to maintain membrane fluidity (PMID:30890562), and possesses intrinsic ceramidase activity that controls retinal ceramide levels, ELOVL2-dependent DHA synthesis, and photoreceptor survival (PMID:35015730, PMID:33963174). Cell-type-specific knockouts further place ADIPOR1 in serotonin and dopamine neuron function and in Th17 differentiation via HIF-1α-driven glycolysis (PMID:31980728, PMID:29988086, PMID:32973810). Its abundance is set post-transcriptionally by miR-221 and the RNA-binding protein PTB acting cooperatively on the 3'UTR (PMID:24130336). Loss-of-function and missense mutations in ADIPOR1 cause autosomal dominant and syndromic retinitis pigmentosa (PMID:27655171, PMID:26662040). ADIPOR1 and ADIPOR2 have divergent in vivo roles, with ADIPOR1 dominating metabolic regulation under diet-induced obesity (PMID:24742672).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2007 High

    Established that ADIPOR1 is genetically required for adiponectin's principal downstream signal, resolving whether the cloned receptor was functionally necessary in vivo.

    Evidence AdipoR1 (and double AdipoR1/R2) knockout mice with adenoviral re-expression and AMPK activation assays

    PMID:17268472

    Open questions at the time
    • Did not define the proximal biochemical event linking receptor to AMPK
    • Tissue-specific contributions not dissected
  2. 2010 High

    Defined the proximal mechanism in muscle, showing ADIPOR1 triggers Ca2+ influx that drives a CaMKKβ/AMPK/SIRT1/PGC-1α cascade and mitochondrial biogenesis.

    Evidence Muscle-specific AdipoR1 knockout mice with Ca2+ imaging and kinase/mitochondrial readouts

    PMID:20357764

    Open questions at the time
    • Channel/mechanism of Ca2+ entry not identified
    • Whether the same Ca2+ step operates in non-muscle tissues unclear
  3. 2009 Medium

    Placed ADIPOR1 upstream of LKB1 in hepatic metabolism, explaining how it suppresses lipogenic SREBP1c.

    Evidence AdipoR1 knockdown plus LKB1 deletion epistasis in hepatocytes and db/db mice

    PMID:19254698

    Open questions at the time
    • How ADIPOR1 activates LKB1 not defined
    • Single lab
  4. 2010 High

    Identified ERp46 as a direct N-terminal interactor controlling ADIPOR1 surface levels and biasing downstream signaling, addressing how receptor trafficking is regulated.

    Evidence Co-IP/MS, GST-truncation domain mapping, fractionation, and knockdown with AMPK/p38 readouts

    PMID:20074551

    Open questions at the time
    • Mechanism by which ERp46 differentially routes AMPK vs p38 signaling unknown
    • Not reconstituted in vitro
  5. 2008 Medium

    Demonstrated receptor-specific roles in inflammation and feeding behavior, broadening ADIPOR1 signaling beyond AMPK to ERK/Src and IRS/STAT pathways.

    Evidence siRNA, icv adiponectin, and pharmacological inhibitors across synovial fibroblasts, vascular/hepatic cells, and hypothalamus

    PMID:17911635 PMID:18394428 PMID:18842004

    Open questions at the time
    • Direct coupling between receptor and Src/Ras not shown
    • Branch-point selection between pathways unexplained
  6. 2014 High

    Established that ADIPOR1 and ADIPOR2 have divergent in vivo physiological roles, with ADIPOR1 dominating metabolic regulation.

    Evidence Separate receptor knockout mice tested in diet-induced obesity and hindlimb ischemia

    PMID:24742672

    Open questions at the time
    • Molecular basis of receptor-specific outputs not resolved
  7. 2013 High

    Revealed post-transcriptional control of ADIPOR1 abundance, explaining receptor downregulation in obesity.

    Evidence RNA-IP and luciferase 3'UTR reporters with gain/loss-of-function for miR-221 and PTB in myogenesis and obesity models

    PMID:24130336

    Open questions at the time
    • Upstream signals controlling miR-221/PTB levels not defined
  8. 2019 High

    Uncovered an adiponectin-independent role: ADIPOR1 maintains membrane fluidity by sustaining desaturase expression, reframing it as a lipid-homeostasis protein.

    Evidence FRAP, Laurdan generalized polarization, and phospholipid lipidomics across multiple human cell types after knockdown

    PMID:30890562

    Open questions at the time
    • How ADIPOR1 controls desaturase expression mechanistically unknown
    • Relation to its ligand-dependent signaling unclear
  9. 2018 High

    Showed ADIPOR1 supports adult vision, with retinal and RPE-specific loss depleting rhodopsin before photoreceptor death.

    Evidence Photoreceptor- and RPE-specific conditional knockouts with ERG and protein expression, plus Mfrprd6 cross-validation

    PMID:30254279

    Open questions at the time
    • Did not establish the biochemical activity driving the requirement
  10. 2022 High

    Identified ADIPOR1 as the dominant retinal ceramidase, providing the enzymatic mechanism linking ADIPOR1 loss to ceramide accumulation, DHA depletion, and photoreceptor degeneration.

    Evidence Knockout mice with scRNA-seq, ceramide/DHA lipidomics, ELOVL2 causal assays, and pharmacological ceramide-lowering rescue

    PMID:33963174 PMID:35015730

    Open questions at the time
    • Catalytic residues and structural basis of ceramidase activity not mapped to function
    • Relationship between ceramidase activity and adiponectin signaling unresolved
  11. 2016 Medium

    Linked ADIPOR1 to inherited retinal disease, establishing causation for retinitis pigmentosa.

    Evidence Exome sequencing of patients with missense (p.Y310C) and frameshift mutations, zebrafish knockdown/mRNA rescue, and retinal IHC

    PMID:26662040 PMID:27655171

    Open questions at the time
    • Mechanism connecting specific mutations to ceramidase/signaling deficits not fully resolved
    • Dominant vs recessive inheritance basis differs between families
  12. 2020 High

    Resolved a closed-to-open conformational transition in the transmembrane cavity, offering structural insight into receptor function.

    Evidence X-ray crystallography of the D208A variant and re-analysis of wild-type diffraction data

    PMID:32796916

    Open questions at the time
    • Conformational state not linked to ligand binding or catalytic cycle
    • No ligand- or substrate-bound structure
  13. 2020 High

    Extended ADIPOR1 to neuronal and immune cell-type-specific control of behavior and Th17 differentiation.

    Evidence Cell-type-specific conditional knockouts in serotonin/dopamine neurons and T cells with electrophysiology, behavior, RNA-seq, and glycolysis assays

    PMID:29988086 PMID:31980728 PMID:32973810

    Open questions at the time
    • Whether these effects require adiponectin, ceramidase activity, or AMPK signaling not disentangled

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ADIPOR1's intrinsic ceramidase activity, its adiponectin-dependent signaling, and its conformational dynamics are mechanistically integrated remains unresolved.
  • No unified model connecting catalysis to signal transduction
  • Structural basis of ligand binding and downstream coupling undefined
  • Direct effector engaging Ca2+ influx and AMPK unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 2 GO:0060089 molecular transducer activity 2 GO:0016787 hydrolase activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005886 plasma membrane 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-162582 Signal Transduction 2 R-HSA-8953854 Metabolism of RNA 2
Partners
APPL1CAVEOLIN-3ERP46LKB1

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 Targeted disruption of AdipoR1 in mice abrogates adiponectin-induced AMPK activation, demonstrating that AdipoR1 is required for adiponectin-mediated AMPK signaling in vivo. Simultaneous disruption of both AdipoR1 and AdipoR2 abolished adiponectin binding entirely. Targeted gene disruption (knockout mice), adenovirus-mediated receptor expression in liver, AMPK activation assays Nature medicine High 17268472
2010 AdipoR1 mediates adiponectin-induced extracellular Ca2+ influx in myocytes, which is required for subsequent activation of CaMKKβ, AMPK, and SIRT1, leading to increased PGC-1α expression and deacetylation, and increased mitochondrial content. Muscle-specific disruption of AdipoR1 suppressed adiponectin-mediated intracellular Ca2+ increases and downstream CaMKK/AMPK/SIRT1 activation. Muscle-specific AdipoR1 knockout mice, intracellular Ca2+ measurements, CaMKK/AMPK/SIRT1 activity assays, mitochondrial content measurements Nature High 20357764
2007 AdipoR1 mediates adiponectin-induced IL-6 production in synovial fibroblasts via an AdipoR1/AMPK/p38/IKKαβ/NF-κB signaling pathway; AdipoR1 siRNA knockdown attenuated adiponectin-mediated AMPK activation, IKK activity, NF-κB nuclear translocation, and IL-6 production. siRNA knockdown of AdipoR1, AMPK kinase activity assays, NF-κB luciferase reporter, IKK activity assays, Western blot for p38 and AMPK phosphorylation Journal of immunology Medium 17911635
2008 AdipoR1, but not AdipoR2, mediates adiponectin's anorexigenic effects in the hypothalamus; AdipoR1 is required for adiponectin-induced activation of IRS1/2, ERK, Akt, FOXO1, JAK2, and STAT3 signaling in the arcuate and lateral hypothalamic nuclei, and for reduction of food intake following icv adiponectin. Intracerebroventricular (icv) adiponectin injection, receptor inhibition, signaling pathway activation assays (Western blot), food intake measurements FEBS letters Medium 18394428
2009 Adiponectin suppresses hepatic SREBP1c expression through AdipoR1 and its upstream kinase LKB1/AMPK pathway; deletion of LKB1 cancelled the negative effect of adiponectin on SREBP1c, placing AdipoR1 upstream of LKB1 in this pathway. AdipoR1 knockdown, LKB1 deletion in hepatocytes, SREBP1c expression assays in db/db mice and cultured hepatocytes Biochemical and biophysical research communications Medium 19254698
2008 AdipoR1 and AdipoR2 activate ERK1/2 through a Src/Ras-dependent pathway in vascular smooth muscle, endothelial cells, and hepatocytes. Downregulation of APPL1 impaired adiponectin-stimulated ERK1/2 activation. Inhibition of Src family tyrosine kinases abolished the response; Clostridium difficile toxin B (Rho/Rac inhibitor) also abolished it. Adiponectin caused Src-dependent Ras activation. RNA interference (siRNA) for AdipoR1/R2 and APPL1, pharmacological inhibitors (PP2 for Src, C. difficile toxin B), Ras and ERK1/2 activation assays, HEK293 cell growth assays Biochemistry Medium 18842004
2010 ERp46 interacts specifically with AdipoR1 (but not AdipoR2) via the cytoplasmic N-terminal residues (1–70) of AdipoR1. ERp46 is present in both the ER and plasma membrane. Knockdown of ERp46 increased AdipoR1 (and AdipoR2) at the plasma membrane, correlated with increased adiponectin-stimulated AMPK phosphorylation, but reduced adiponectin-stimulated p38MAPK phosphorylation. Co-immunoprecipitation followed by mass spectrometry, GST-fusion protein pulldowns with truncation constructs, indirect immunofluorescence, subcellular fractionation, siRNA knockdown, AMPK and p38MAPK phosphorylation assays Biochemical and biophysical research communications High 20074551
2011 AdipoR1 mediates adiponectin-induced MMP-3 expression in human chondrocytes via AdipoR1/AMPK/p38/NF-κB pathway; AdipoR1 (but not AdipoR2) siRNA knockdown attenuated this response. siRNA knockdown of AdipoR1 vs AdipoR2, qPCR, Western blot, ELISA for MMP-3, kinase inhibitor assays (AMPK inhibitor, p38 inhibitor, NF-κB inhibitor) Journal of cellular biochemistry Medium 21321996
2011 Globular adiponectin protects H9c2 cardiomyocytes from hypoxia/reoxygenation-induced apoptosis via AdipoR1/APPL1 signaling; AdipoR1 siRNA knockdown attenuated adiponectin's anti-oxidative and anti-apoptotic effects (ROS reduction and caspase-3 activity), and APPL1 knockdown similarly abrogated these protective effects. siRNA knockdown of AdipoR1 and APPL1, TUNEL/annexin V apoptosis assays, cytochrome c release, caspase-3 activation, ROS measurement PloS one Medium 21552570
2011 AdipoR1 is required for adiponectin-induced suppression of NF-κB in lung epithelial A549 cells; AdipoR1 siRNA silencing abrogated NF-κB nuclear trans-activation by adiponectin, whereas AdipoR2 knockdown did not affect this response. siRNA knockdown of AdipoR1 vs AdipoR2, NF-κB nuclear trans-activation assay, ERK1/2 and AKT signaling, cell viability assay The international journal of biochemistry & cell biology Medium 23500159
2011 AdipoR1 is required by adiponectin to suppress TNFα and MCP-1 gene expression in macrophage foam cells; APPL1 knockdown abrogated adiponectin-mediated inhibition of lipid accumulation, SR-AI, NF-κB gene expression, and Akt phosphorylation. AdipoR1 and AdipoR2 have differential roles: AdipoR2 dominantly mediates suppression of SR-AI and upregulation of IL-1Ra. Overexpression and knockdown of AdipoR1/AdipoR2, lentiviral shRNA knockdown of APPL1, foam cell formation assay with oxLDL, cytokine gene expression, Akt phosphorylation Atherosclerosis Medium 22227293
2009 Adiponectin inhibits LPS-induced adventitial fibroblast migration and transformation to myofibroblasts via AdipoR1/AMPK/iNOS pathway; AdipoR1 siRNA reversed adiponectin's inhibition of AMPK phosphorylation and iNOS/NO/ONOO- production induced by LPS. siRNA knockdown of AdipoR1 and AMPK, siAMPK, AMPK inhibitor, migration/scratch-wound assays, iNOS RT-PCR and Western blot, NO and ONOO- assays, in vivo adenovirus-adiponectin in ApoE-KO mice Molecular endocrinology Medium 19889816
2008 In renal distal tubules, adiponectin acts through luminal AdipoR1 (not AdipoR2, which was undetected) to activate AMPK, leading to inhibition of glycogen synthase (GS). In diabetic rats, this AdipoR1/AMPK regulation is impaired, correlating with glycogen accumulation. Western blot of isolated distal tubules, immunohistochemistry, in vitro AICAR and globular adiponectin treatment of isolated tubules from normal and STZ-diabetic rats, GS activity assays American journal of physiology. Renal physiology Medium 18256313
2015 AdipoR1 mediates ischemic postconditioning (IPo) cardioprotection through an APN/AdipoR1/Caveolin-3 pathway that activates mitochondrial STAT3 (mitoSTAT3). Specific AdipoR1 gene knockdown or caveolin-3 disruption abolished adiponectin's ability to activate STAT3 and confer cardioprotection. In diabetes, impaired AdipoR1/Cav3 signaling underlies loss of IPo cardioprotection. AdipoR1 siRNA knockdown, caveolin-3 disruption, APN knockout mice, STAT3 activation assays, myocardial I/R injury model, mitochondrial STAT3 fractionation Diabetes Medium 26718505
2016 A heterozygous missense mutation in ADIPOR1 (p.Y310C) causes autosomal dominant retinitis pigmentosa; the mutation affects protein folding and subcellular localization in vitro. Knockdown of adipor1 in zebrafish preferentially reduces rod photoreceptors, and the phenotype is rescued by wild-type but not mutant human ADIPOR1 mRNA. Exome sequencing, in vitro expression with localization studies (protein folding/localization), zebrafish morpholino knockdown, mRNA rescue experiment Human genetics Medium 27655171
2016 ADIPOR1 is identified as a novel disease-causing gene for syndromic retinitis pigmentosa; a homozygous frameshift mutation (c.31delC, p.Q11Rfs*24) was found in a patient with retinal dystrophy, obesity, and behavioral abnormalities — a phenotype mirrored by Adipor1-null mice. ADIPOR1 expression was confirmed in retina by immunohistochemistry. Whole-exome sequencing, variant filtering, immunohistochemistry of retina Human mutation Medium 26662040
2018 Post-developmental knockout of AdipoR1 in photoreceptors or in the retinal pigment epithelium (RPE) results in decreased expression of retinal proteins and depletes RHODOPSIN prior to photoreceptor death, establishing a role for ADIPOR1 in supporting vision in adulthood. Loss of ADIPOR1 in the RPE layer alone (as in Mfrprd6 mice) is sufficient to drive retinal degeneration. Conditional (cell-type-specific) AdipoR1 knockout mice (photoreceptor-specific and RPE-specific), electroretinography, retinal protein expression analysis, comparison with Mfrprd6 mouse model Scientific reports High 30254279
2022 Absence of AdipoR1 in mice leads to ceramide accumulation in the retina due to insufficient ceramidase activity, causing photoreceptor degeneration. Single-cell RNA-seq identified ADIPOR1 as the most abundantly expressed ceramidase in mouse retina and one of the two most highly expressed in human retina. Pharmacological reduction of ceramides with desipramine/L-cycloserine rescued photoreceptors and improved visual function in AdipoR1 KO mice. AdipoR1 knockout mice, single-cell RNA-seq, ceramide mass spectrometry, electroretinography, visual cortex electrophysiology, pharmacological treatment (desipramine/L-cycloserine), in vitro causal relationship assay for ELOVL2 JCI insight High 35015730
2021 ADIPOR1 deficiency in the retina suppresses ELOVL2 expression and reduces docosahexaenoic acid (DHA) levels, which are critical for photoreceptor outer segment formation. This causal relationship between ADIPOR1 deficiency and ELOVL2 repression was confirmed in vitro, and lipogenic gene upregulation consistent with reduced endogenous DHA synthesis was observed. Adipor1 knockout mice, electroretinography, electron microscopy, lipid composition analysis (mass spectrometry), ELOVL2 mRNA and protein assays, in vitro causal confirmation Cell death & disease Medium 33963174
2019 AdipoR1 maintains membrane fluidity in most human cell types independently of adiponectin, by sustaining desaturase expression and high levels of unsaturated fatty acids in membrane phospholipids and preventing membrane rigidification under palmitate challenge. This was demonstrated without exogenous adiponectin, showing AdipoR1 has an adiponectin-independent lipid homeostasis function. AdipoR1/AdipoR2 knockdown in multiple human cell types (including primary HUVECs), FRAP (fluorescence recovery after photobleaching), Laurdan dye generalized polarization, mass spectrometry of phospholipid FA composition Journal of lipid research High 30890562
2020 Crystal structure determination of the D208A variant AdipoR1 reveals a closed-open interconversion of the receptor's internal cavity: helices IV and V tilt with intracellular ends shifting ~4 and ~11 Å respectively between closed and open forms. Re-analysis of wild-type AdipoR1 diffraction data showed a 44:56 mixture of closed and open forms, suggesting this conformational change is relevant to receptor function. X-ray crystallography of D208A AdipoR1 variant, re-analysis of wild-type AdipoR1 diffraction data, structural comparison of asymmetric unit molecules Communications biology High 32796916
2013 AdipoR1 translation is co-regulated post-transcriptionally by both miR-221 and the RNA-binding protein PTB (polypyrimidine tract-binding protein) acting on the AdipoR1 3'UTR. PTB and miR-221 cooperatively inhibit AdipoR1 protein synthesis; depletion of either increases AdipoR1 protein, and overexpression decreases it. During myogenesis, downregulation of PTB and miR-221 induces AdipoR1 translation. RNA immunoprecipitation, luciferase reporter assays (3'UTR), siRNA depletion and overexpression of PTB and miR-221, myogenesis differentiation model, mouse obesity models Diabetes High 24130336
2012 AdipoR1 overexpression in rat skeletal muscle increases glucose uptake, glycogen accumulation, IRS-1/Akt/GSK-3β phosphorylation, AMPK/ACC phosphorylation, APPL1 protein levels, PGC-1α and UCP3 expression, and reduces specific ceramide species and ceramide synthetic enzyme mRNAs, thereby locally ameliorating insulin resistance. In vivo electrotransfer-mediated AdipoR1 overexpression in single muscles, hyperinsulinemic-euglycemic clamp, glucose uptake measurement, sphingolipid mass spectrometry, Western blot for multiple signaling proteins Endocrinology Medium 22989629
2018 AdipoR1 is expressed in serotonin (5-HT) neurons of the dorsal raphe nucleus; selective deletion of AdipoR1 in 5-HT neurons reduces TPH2 expression and 5-HT immunoreactivity in DRN, hippocampus, and mPFC in male mice, increases SERT expression, and causes depression-related behavioral phenotypes in a sex-dependent manner. Conditional (5-HT neuron-specific) AdipoR1 knockout mice, immunofluorescence co-localization (AdipoR1/TPH2), behavioral tests (saccharin preference, forced swim, sucrose preference), immunohistochemistry for TPH2, SERT, 5-HT, pharmacological test with fluoxetine vs desipramine Molecular psychiatry High 31980728
2018 AdipoR1 is expressed in VTA dopamine neurons; ablation of AdipoR1 specifically from dopamine neurons enhances neuronal firing and anxiogenic responses to stress. Intra-VTA adiponectin infusion decreases basal dopamine neuron firing and reverses stress-induced increases in activity, and these effects are abolished in mice lacking AdipoR1 in dopamine neurons. Dopamine neuron-specific AdipoR1 knockout mice, intra-VTA adiponectin/AdipoRon infusion, in vivo electrophysiology (dopamine neuron firing rate and population activity), behavioral anxiety tests, adiponectin haploinsufficiency model Molecular psychiatry High 29988086
2018 Adiponectin attenuates neuronal apoptosis after neonatal hypoxia-ischemia via AdipoR1/APPL1/LKB1/AMPK signaling pathway; siRNA knockdown of AdipoR1, APPL1, or LKB1 abolished the anti-apoptotic effects of recombinant adiponectin, placing them in an epistatic pathway. Intracerebroventricular siRNA for AdipoR1, APPL1, LKB1 in neonatal rats, intranasal recombinant adiponectin, brain infarct measurement, TUNEL/FJC staining, Western blot for LKB1, p-AMPK, Cleaved-Caspase 3 Neuropharmacology Medium 29486166
2019 AdipoR1 knockdown in BV2 microglia inhibited adiponectin's ability to suppress AβO-induced TNFα and IL-1β release and to prevent the AβO-induced decrease in AMPK phosphorylation and NF-κB nuclear translocation. AdipoR2 knockdown had no such effect, establishing AdipoR1-specific mediation of APN's anti-inflammatory effects in microglia. siRNA knockdown of AdipoR1 vs AdipoR2, AMPK inhibitor (compound C), ELISA for cytokines, Western blot for p-AMPK, immunofluorescence for NF-κB nuclear translocation, MTT assay for neuroprotection, APN-/-5xFAD mice Journal of neuroinflammation Medium 31128596
2014 AdipoR1-deficient mice develop severe metabolic dysfunction under diet-induced obesity, whereas AdipoR2-deficient mice are protected, demonstrating divergent in vivo metabolic roles for the two receptors. In contrast, AdipoR2 (not AdipoR1) is functionally required for revascularization in hindlimb ischemia and for the revascularization actions of adiponectin. AdipoR1 and AdipoR2 knockout mice, chronic hindlimb ischemia surgery, blood flow recovery measurement, diet-induced obesity model, metabolic phenotyping The Journal of biological chemistry High 24742672
2022 Ionizing radiation upregulates AdipoR1 expression in HCC cells, which promotes Nrf2 protein stability; Nrf2 then binds the xCT promoter to increase xCT transcription, reducing ferroptosis. AdipoR1 knockdown inhibited Nrf2 and xCT expression and increased IR-induced and erastin-induced ferroptosis; this was rescued by Nrf2 or xCT restoration. AdipoR1 siRNA knockdown, Nrf2 rescue, xCT rescue, xCT promoter-Nrf2 binding assay, ferroptosis assays (cell death, lipid peroxidation), erastin treatment Oxidative medicine and cellular longevity Medium 35733794
2020 AdipoR1 deficiency in T cells inhibits Th17 cell differentiation in vitro and ameliorates joint inflammation in antigen-induced arthritis mice. Mechanistically, AdipoR1 knockout reduced HIF-1α expression, leading to glycolysis inhibition during naïve CD4+ T cell differentiation into Th17 cells; RNAseq showed greatest downregulation of Rorc in AdipoR1-KO T cells. T cell lineage-specific AdipoR1 conditional knockout, RNA-sequencing, Th17 differentiation assays in vitro, antigen-induced arthritis in vivo model, HIF-1α expression and glycolysis assays Frontiers in immunology Medium 32973810
2017 Globular adiponectin exerts anti-inflammatory and anti-oxidant actions on microglia via an AdipoR1/NF-κB signaling pathway; AdipoR1 (but not AdipoR2) knockdown abolished these effects in BV2 cells and primary microglia. siRNA knockdown of AdipoR1 vs AdipoR2, NF-κB pathway assays, cytokine measurement (IL-1β, IL-6, TNFα), nitrosative/oxidative stress measurement in microglia, in vivo LPS challenge in APN-deficient mice Frontiers in cellular neuroscience Medium 29184485
2011 Globular adiponectin counteracts VCAM-1-mediated monocyte adhesion in human aortic endothelial cells via AdipoR1/NF-κB/COX-2 signaling; in HAEC lacking AdipoR1 (by siRNA), gAd-mediated NF-κB activation and COX-2 overexpression were abrogated, and monocyte adhesion was greatly enhanced. The p38MAPK/VCAM-1 pathway was AdipoR1-independent. siRNA knockdown of AdipoR1 and COX-2, NF-κB activation assays, COX-2/PGI2 measurement, VCAM-1 expression, monocyte adhesion assay, p38MAPK phosphorylation American journal of physiology. Endocrinology and metabolism Medium 21900123
2014 AdipoR1 and APPL1 mediate globular adiponectin's protective effects against angiotensin II-induced atrial hypertrophy and fibrosis; siRNA-mediated suppression of AdipoR1 or APPL1 diminished gAcrp-induced AMPK phosphorylation and its downstream suppression of NF-κB, and the effect of adiponectin required PI3K/Akt. siRNA knockdown of AdipoR1 and APPL1 in neonatal rat atrial cells, EMSA supershift for NF-κB p65/p50, PI3K inhibitor, AMPK phosphorylation assay, real-time PCR for hypertrophy/fibrosis markers PloS one Medium 25099270
2022 AdipoR1 is directly targeted by Schisandrin A (which reduces LPS+ATP-induced AdipoR1 ubiquitination in vitro), and Schisandrin A activates AdipoR1/AMPK signaling while suppressing TXNIP/NLRP3 pathway to attenuate ferroptosis and pyroptosis in diabetic nephropathy models. In vitro DN model (high glucose endothelial cells), in vivo STZ/high-fat diet mouse model, AdipoR1 direct targeting assay, ubiquitination assay, AMPK and NLRP3 pathway analyses Oxidative medicine and cellular longevity Low 35996380
2013 PTB and miR-221 bind the AdipoR1 3'UTR and cooperatively inhibit AdipoR1 translation; upregulation of both PTB and miR-221 in obesity models reduces AdipoR1 protein levels, providing a translational mechanism for reduced AdipoR1 in obesity. RNA immunoprecipitation, luciferase reporter assays, siRNA depletion and overexpression, genetic and dietary obesity mouse models Diabetes High 24130336

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nature medicine 1117 17268472
2010 Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1. Nature 836 20357764
2007 Adiponectin enhances IL-6 production in human synovial fibroblast via an AdipoR1 receptor, AMPK, p38, and NF-kappa B pathway. Journal of immunology (Baltimore, Md. : 1950) 216 17911635
2010 Adiponectin represses colon cancer cell proliferation via AdipoR1- and -R2-mediated AMPK activation. Molecular endocrinology (Baltimore, Md.) 176 20444885
2016 Novel osmotin inhibits SREBP2 via the AdipoR1/AMPK/SIRT1 pathway to improve Alzheimer's disease neuropathological deficits. Molecular psychiatry 173 27001618
2013 The large non-coding RNA ANRIL, which is associated with atherosclerosis, periodontitis and several forms of cancer, regulates ADIPOR1, VAMP3 and C11ORF10. Human molecular genetics 171 23813974
2009 Adiponectin suppresses hepatic SREBP1c expression in an AdipoR1/LKB1/AMPK dependent pathway. Biochemical and biophysical research communications 154 19254698
2019 Adiponectin suppresses amyloid-β oligomer (AβO)-induced inflammatory response of microglia via AdipoR1-AMPK-NF-κB signaling pathway. Journal of neuroinflammation 143 31128596
2008 AdipoR1 mediates the anorexigenic and insulin/leptin-like actions of adiponectin in the hypothalamus. FEBS letters 125 18394428
2018 LncRNA ANRIL regulates AML development through modulating the glucose metabolism pathway of AdipoR1/AMPK/SIRT1. Molecular cancer 121 30134922
2020 AdipoR1/AdipoR2 dual agonist recovers nonalcoholic steatohepatitis and related fibrosis via endoplasmic reticulum-mitochondria axis. Nature communications 120 33199780
2006 Expression of adiponectin and its receptors (AdipoR1 and AdipoR2) in chicken ovary: potential role in ovarian steroidogenesis. Domestic animal endocrinology 112 17010558
2008 Variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes and colorectal cancer risk. JAMA 109 18827209
2008 The adiponectin receptors AdipoR1 and AdipoR2 activate ERK1/2 through a Src/Ras-dependent pathway and stimulate cell growth. Biochemistry 107 18842004
2022 Schisandrin A from Schisandra chinensis Attenuates Ferroptosis and NLRP3 Inflammasome-Mediated Pyroptosis in Diabetic Nephropathy through Mitochondrial Damage by AdipoR1 Ubiquitination. Oxidative medicine and cellular longevity 95 35996380
2016 Resveratrol increases AdipoR1 and AdipoR2 expression in type 2 diabetic nephropathy. Journal of translational medicine 93 27286657
2013 Adiponectin affects lung epithelial A549 cell viability counteracting TNFα and IL-1ß toxicity through AdipoR1. The international journal of biochemistry & cell biology 88 23500159
2011 Adiponectin increases MMP-3 expression in human chondrocytes through AdipoR1 signaling pathway. Journal of cellular biochemistry 79 21321996
2011 Adiponectin-AdipoR1/2-APPL1 signaling axis suppresses human foam cell formation: differential ability of AdipoR1 and AdipoR2 to regulate inflammatory cytokine responses. Atherosclerosis 78 22227293
2015 Hyperglycemia Abrogates Ischemic Postconditioning Cardioprotection by Impairing AdipoR1/Caveolin-3/STAT3 Signaling in Diabetic Rats. Diabetes 77 26718505
2018 Adiponectin attenuates neuronal apoptosis induced by hypoxia-ischemia via the activation of AdipoR1/APPL1/LKB1/AMPK pathway in neonatal rats. Neuropharmacology 76 29486166
2016 Exercise restores muscle stem cell mobilization, regenerative capacity and muscle metabolic alterations via adiponectin/AdipoR1 activation in SAMP10 mice. Journal of cachexia, sarcopenia and muscle 76 27897419
2004 Adiponectin receptor 1 gene (ADIPOR1) as a candidate for type 2 diabetes and insulin resistance. Diabetes 74 15277397
2009 Role of adiponectin receptors, AdipoR1 and AdipoR2, in the steroidogenesis of the human granulosa tumor cell line, KGN. Human reproduction (Oxford, England) 71 19671624
2011 Globular adiponectin, acting via AdipoR1/APPL1, protects H9c2 cells from hypoxia/reoxygenation-induced apoptosis. PloS one 70 21552570
2024 Running exercise alleviates hippocampal neuroinflammation and shifts the balance of microglial M1/M2 polarization through adiponectin/AdipoR1 pathway activation in mice exposed to chronic unpredictable stress. Molecular psychiatry 67 38361125
2020 Modulation of depression-related behaviors by adiponectin AdipoR1 receptors in 5-HT neurons. Molecular psychiatry 67 31980728
2013 A comprehensive investigation of variants in genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1/R2), and their association with serum adiponectin, type 2 diabetes, insulin resistance and the metabolic syndrome. BMC medical genetics 65 23351195
2018 Adiponectin modulates ventral tegmental area dopamine neuron activity and anxiety-related behavior through AdipoR1. Molecular psychiatry 64 29988086
2008 Control of glycogen synthase through ADIPOR1-AMPK pathway in renal distal tubules of normal and diabetic rats. American journal of physiology. Renal physiology 64 18256313
2008 Adiponectin and its receptors are expressed in the chicken testis: influence of sexual maturation on testicular ADIPOR1 and ADIPOR2 mRNA abundance. Reproduction (Cambridge, England) 62 18660386
2019 AdipoR1 and AdipoR2 maintain membrane fluidity in most human cell types and independently of adiponectin. Journal of lipid research 60 30890562
2006 Molecular cloning and tissue expression of chicken AdipoR1 and AdipoR2 complementary deoxyribonucleic acids. Domestic animal endocrinology 60 16697136
2012 Overexpression of the adiponectin receptor AdipoR1 in rat skeletal muscle amplifies local insulin sensitivity. Endocrinology 58 22989629
2017 Adiponectin controls the apoptosis and the expression of tight junction proteins in brain endothelial cells through AdipoR1 under beta amyloid toxicity. Cell death & disease 57 29022894
2010 ERp46 binds to AdipoR1, but not AdipoR2, and modulates adiponectin signalling. Biochemical and biophysical research communications 57 20074551
2009 Adiponectin inhibits lipopolysaccharide-induced adventitial fibroblast migration and transition to myofibroblasts via AdipoR1-AMPK-iNOS pathway. Molecular endocrinology (Baltimore, Md.) 57 19889816
2020 AdipoRon improves cognitive dysfunction of Alzheimer's disease and rescues impaired neural stem cell proliferation through AdipoR1/AMPK pathway. Experimental neurology 56 32070713
2017 CTRP6 Regulates Porcine Adipocyte Proliferation and Differentiation by the AdipoR1/MAPK Signaling Pathway. Journal of agricultural and food chemistry 56 28535682
2008 Expression of adiponectin receptors, AdipoR1 and AdipoR2, in normal colon epithelium and colon cancer tissue. Oncology reports 56 18695895
2020 Tectorigenin attenuates diabetic nephropathy by improving vascular endothelium dysfunction through activating AdipoR1/2 pathway. Pharmacological research 54 32014572
2017 Globular Adiponectin Limits Microglia Pro-Inflammatory Phenotype through an AdipoR1/NF-κB Signaling Pathway. Frontiers in cellular neuroscience 52 29184485
2020 Genistein inhibits high fat diet-induced obesity through miR-222 by targeting BTG2 and adipor1. Food & function 51 32129363
2019 Resveratrol regulates skeletal muscle fibers switching through the AdipoR1-AMPK-PGC-1α pathway. Food & function 51 31095141
2011 Polymorphisms of ADIPOQ and ADIPOR1 and prostate cancer risk. Metabolism: clinical and experimental 48 21397927
2013 RNA-binding protein PTB and microRNA-221 coregulate AdipoR1 translation and adiponectin signaling. Diabetes 47 24130336
2019 AdipoRon Attenuates Neuroinflammation After Intracerebral Hemorrhage Through AdipoR1-AMPK Pathway. Neuroscience 46 31176703
2016 A mutation in ADIPOR1 causes nonsyndromic autosomal dominant retinitis pigmentosa. Human genetics 45 27655171
2023 Neuroprotective effects of osmotin in Parkinson's disease-associated pathology via the AdipoR1/MAPK/AMPK/mTOR signaling pathways. Journal of biomedical science 44 37568205
2010 Genetic variation in adiponectin (ADIPOQ) and the type 1 receptor (ADIPOR1), obesity and prostate cancer in African Americans. Prostate cancer and prostatic diseases 42 20697428
2016 ADIPOR1 Is Mutated in Syndromic Retinitis Pigmentosa. Human mutation 41 26662040
2011 Globular adiponectin counteracts VCAM-1-mediated monocyte adhesion via AdipoR1/NF-κB/COX-2 signaling in human aortic endothelial cells. American journal of physiology. Endocrinology and metabolism 41 21900123
2006 Association of sequence variations in the gene encoding adiponectin receptor 1 (ADIPOR1) with body size and insulin levels. The Finnish Diabetes Prevention Study. Diabetologia 40 16724230
2022 Adiponectin Ameliorates GMH-Induced Brain Injury by Regulating Microglia M1/M2 Polarization Via AdipoR1/APPL1/AMPK/PPARγ Signaling Pathway in Neonatal Rats. Frontiers in immunology 39 35720361
2018 ADIPOR1 is essential for vision and its RPE expression is lost in the Mfrprd6 mouse. Scientific reports 39 30254279
2012 Adiponectin receptor 1 gene (ADIPOR1) variant is associated with advanced age-related macular degeneration in Finnish population. Neuroscience letters 39 22387454
2011 ADIPOQ, ADIPOR1, and ADIPOR2 polymorphisms in relation to serum adiponectin levels and BMI in black and white women. Obesity (Silver Spring, Md.) 39 21273992
2006 Expression of the adiponectin receptors AdipoR1 and AdipoR2 in lean rats and in obese Zucker rats. Metabolism: clinical and experimental 39 16483885
2014 Divergent roles for adiponectin receptor 1 (AdipoR1) and AdipoR2 in mediating revascularization and metabolic dysfunction in vivo. The Journal of biological chemistry 38 24742672
2014 AdipoR1/APPL1 potentiates the protective effects of globular adiponectin on angiotensin II-induced cardiac hypertrophy and fibrosis in neonatal rat atrial myocytes and fibroblasts. PloS one 37 25099270
2012 Exercise training performed simultaneously to a high-fat diet reduces the degree of insulin resistance and improves adipoR1-2/APPL1 protein levels in mice. Lipids in health and disease 37 23046739
2008 The association of SNPs in ADIPOQ, ADIPOR1, and ADIPOR2 with insulin sensitivity in a cohort of adolescents and their parents. Human genetics 37 19037660
2013 Expression of adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) in the porcine pituitary during the oestrous cycle. Reproductive biology and endocrinology : RB&E 36 23497348
2021 Adiponectin/AdipoR1 Axis Promotes IL-10 Release by Human Regulatory T Cells. Frontiers in immunology 35 34084174
2020 Nobiletin alleviates high-fat diet-induced nonalcoholic fatty liver disease by modulating AdipoR1 and gp91phox expression in rats. The Journal of nutritional biochemistry 35 33096235
2019 Adiponectin Protects Against Cerebral Ischemic Injury Through AdipoR1/AMPK Pathways. Frontiers in pharmacology 35 31231213
2022 Inhibition of ceramide accumulation in AdipoR1-/- mice increases photoreceptor survival and improves vision. JCI insight 34 35015730
2010 Regulation of synthesis and oxidation of fatty acids by adiponectin receptors (AdipoR1/R2) and insulin receptor substrate isoforms (IRS-1/-2) of the liver in a nonalcoholic steatohepatitis animal model. Metabolism: clinical and experimental 34 20846698
2021 ADIPOR1 deficiency-induced suppression of retinal ELOVL2 and docosahexaenoic acid levels during photoreceptor degeneration and visual loss. Cell death & disease 32 33963174
2017 Osmotin Protects H9c2 Cells from Simulated Ischemia-Reperfusion Injury through AdipoR1/PI3K/AKT Signaling Pathway. Frontiers in physiology 32 28993734
2014 Expression of adiponectin and adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) in the porcine uterus during the oestrous cycle. Animal reproduction science 32 24598213
2011 HTR1B, ADIPOR1, PPARGC1A, and CYP19A1 and obesity in a cohort of Caucasians and African Americans: an evaluation of gene-environment interactions and candidate genes. American journal of epidemiology 32 22106445
2021 Empagliflozin Regulates the AdipoR1/p-AMPK/p-ACC Pathway to Alleviate Lipid Deposition in Diabetic Nephropathy. Diabetes, metabolic syndrome and obesity : targets and therapy 31 33500643
2007 Polymorphisms in adiponectin receptor genes ADIPOR1 and ADIPOR2 and insulin resistance. Obesity reviews : an official journal of the International Association for the Study of Obesity 30 17716299
2020 Nobiletin ameliorates high-fat diet-induced vascular and renal changes by reducing inflammation with modulating AdipoR1 and TGF-β1 expression in rats. Life sciences 29 32920004
2017 The role of AdipoR1 and AdipoR2 in liver fibrosis. Biochimica et biophysica acta. Molecular basis of disease 29 29237572
2018 The Adiponectin Homolog Osmotin Enhances Neurite Outgrowth and Synaptic Complexity via AdipoR1/NgR1 Signaling in Alzheimer's Disease. Molecular neurobiology 28 29335844
2016 Lipogenesis in myoblasts and its regulation of CTRP6 by AdipoR1/Erk/PPARγ signaling pathway. Acta biochimica et biophysica Sinica 28 27125977
2015 Pioglitazone treatment increases food intake and decreases energy expenditure partially via hypothalamic adiponectin/adipoR1/AMPK pathway. International journal of obesity (2005) 28 26228462
2022 Aerobic Exercise Alleviates Abnormal Autophagy in Brain Cells of APP/PS1 Mice by Upregulating AdipoR1 Levels. International journal of molecular sciences 27 36077318
2020 Critical Role of AdipoR1 in Regulating Th17 Cell Differentiation Through Modulation of HIF-1α-Dependent Glycolysis. Frontiers in immunology 26 32973810
2019 6-Gingerol Improves Ectopic Lipid Accumulation, Mitochondrial Dysfunction, and Insulin Resistance in Skeletal Muscle of Ageing Rats: Dual Stimulation of the AMPK/PGC-1α Signaling Pathway via Plasma Adiponectin and Muscular AdipoR1. Molecular nutrition & food research 26 30575271
2022 AdipoR1 Regulates Ionizing Radiation-Induced Ferroptosis in HCC cells through Nrf2/xCT Pathway. Oxidative medicine and cellular longevity 25 35733794
2021 CTRP9 Enhances Efferocytosis in Macrophages via MAPK/Drp1-Mediated Mitochondrial Fission and AdipoR1-Induced Immunometabolism. Journal of inflammation research 25 33790616
2021 Galangin Resolves Cardiometabolic Disorders through Modulation of AdipoR1, COX-2, and NF-κB Expression in Rats Fed a High-Fat Diet. Antioxidants (Basel, Switzerland) 25 34066039
2017 MiR-221 mediates the epithelial-mesenchymal transition of hepatocellular carcinoma by targeting AdipoR1. International journal of biological macromolecules 25 28539268
2022 Synergistic activation of AMPK by AdipoR1/2 agonist and inhibitor of EDPs-EBP interaction recover NAFLD through enhancing mitochondrial function in mice. Acta pharmaceutica Sinica. B 24 36873175
2010 Impact of AdipoR1 expression on breast cancer development. Gynecologic oncology 24 20071013
2014 The effect of resveratrol on the expression of AdipoR1 in kidneys of diabetic nephropathy. Molecular biology reports 23 24413998
2019 Administration of rCTRP9 Attenuates Neuronal Apoptosis Through AdipoR1/PI3K/Akt Signaling Pathway after ICH in Mice. Cell transplantation 21 30642187
2020 Human adiponectin receptor AdipoR1 assumes closed and open structures. Communications biology 20 32796916
2020 LncRNA loc105377478 promotes NPs-Nd2O3-induced inflammation in human bronchial epithelial cells through the ADIPOR1/NF-κB axis. Ecotoxicology and environmental safety 20 33396129
2019 The Adiponectin-AdipoR1 Axis Mediates Tumor Progression and Tyrosine Kinase Inhibitor Resistance in Metastatic Renal Cell Carcinoma. Neoplasia (New York, N.Y.) 20 31401413
2022 Molecular modeling, mutational analysis and steroid specificity of the ligand binding pocket of mPRα (PAQR7): Shared ligand binding with AdipoR1 and its structural basis. The Journal of steroid biochemistry and molecular biology 19 35189329
2021 Activation of AdipoR1 with rCTRP9 Preserves BBB Integrity through the APPL1/AMPK/Nrf2 Signaling Pathway in ICH Mice. Oxidative medicine and cellular longevity 19 34925690
2013 Single-nucleotide polymorphisms in adiponectin, AdipoR1, and AdipoR2 genes: insulin resistance and type 2 diabetes mellitus candidate genes. American journal of therapeutics 19 23656997
2017 Expression of adiponectin and its receptors (AdipoR1 and AdipoR2) in goat ovary and its effect on oocyte nuclear maturation in vitro. Theriogenology 18 28843075
2021 Perivascular adipose tissue and microvascular endothelial dysfunction in obese mice: Beneficial effects of aerobic exercise in adiponectin receptor (AdipoR1) and peNOSSer1177. Clinical and experimental pharmacology & physiology 17 34260769
2017 AdipoR1-mediated miR-3908 inhibits glioblastoma tumorigenicity through downregulation of STAT2 associated with the AMPK/SIRT1 pathway. Oncology reports 17 28440504
2015 Molecular cloning and expression analysis of adiponectin and its receptors (AdipoR1 and AdipoR2) in the hypothalamus of the Huoyan goose during different stages of the egg-laying cycle. Reproductive biology and endocrinology : RB&E 17 26251033

Missed literature

Know a paper Affinage missed for ADIPOR1? Flag it for the maintainers and the community.

No submissions yet.