Affinage

ADIPOR1

Adiponectin receptor protein 1 · UniProt Q96A54

Length
375 aa
Mass
42.6 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADIPOR1 is a seven-transmembrane adiponectin receptor that functions as a central metabolic sensor coupling adiponectin signaling to AMPK activation, mitochondrial biogenesis, lipid homeostasis, and anti-inflammatory responses across diverse tissues including skeletal muscle, liver, brain, retina, and immune cells. Upon adiponectin binding, ADIPOR1 induces extracellular Ca²⁺ influx to activate CaMKKβ→AMPK→SIRT1→PGC-1α signaling, promoting mitochondrial content and exercise capacity, and signals through APPL1→LKB1→AMPK to suppress hepatic gluconeogenesis and SREBP1c-driven lipogenesis (PMID:20357764, PMID:19254698, PMID:17268472). ADIPOR1 also possesses intrinsic ceramidase activity essential for maintaining membrane phospholipid unsaturation and DHA levels in photoreceptor outer segments; loss of this activity causes ceramide accumulation and retinal degeneration, and heterozygous or homozygous ADIPOR1 mutations cause retinitis pigmentosa in humans (PMID:35015730, PMID:30890562, PMID:27655171, PMID:26662040). In the brain, cell-type-specific ADIPOR1 deletion in serotonergic or dopaminergic neurons disrupts neurotransmitter homeostasis and produces depression- and anxiety-related phenotypes, while its surface availability is regulated post-translationally by ERp46 retention and translationally by miR-221/PTB-mediated repression (PMID:31980728, PMID:29988086, PMID:20074551, PMID:24130336).

Mechanistic history

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

    Establishing that ADIPOR1 and ADIPOR2 are the principal in vivo adiponectin receptors — and that ADIPOR1 specifically mediates AMPK activation — resolved the long-standing question of receptor identity for adiponectin signaling.

    Evidence Targeted gene disruption (single and double KO mice) with metabolic phenotyping and adiponectin binding assays

    PMID:17268472

    Open questions at the time
    • Mechanism by which ADIPOR1 selectively activates AMPK over other kinases was not defined
    • Ligand-independent functions not addressed
  2. 2008 Medium

    Demonstrating AdipoR1-dependent signaling in hypothalamus (anorexigenic) and renal tubules (glycogen synthase inhibition) extended the receptor's functional reach beyond skeletal muscle and liver to brain and kidney.

    Evidence ICV adiponectin with receptor inhibition and behavioral/signaling readouts; immunohistochemistry and AMPK activity assays in isolated renal tubules

    PMID:18256313 PMID:18394428

    Open questions at the time
    • Receptor subtype specificity relied on pharmacological inhibition rather than genetic deletion in the hypothalamic study
    • Downstream mediators linking AMPK to behavioral output not identified
  3. 2009 Medium

    Identification of LKB1 as a required intermediate between ADIPOR1 and AMPK-mediated SREBP1c suppression, and of the ADIPOR1–AMPK–iNOS axis in fibroblast migration, established branching downstream pathway architecture.

    Evidence LKB1-deleted hepatocytes and AdipoR1/AMPK siRNA in fibroblasts with epistasis analysis

    PMID:19254698 PMID:19889816

    Open questions at the time
    • Whether LKB1 vs. CaMKKβ dominance is tissue-specific was not resolved
    • Direct physical interaction between ADIPOR1 and LKB1 not shown
  4. 2010 High

    The discovery that ADIPOR1 triggers extracellular Ca²⁺ influx to activate CaMKKβ→AMPK→SIRT1→PGC-1α, driving mitochondrial biogenesis and exercise endurance, defined the core muscle signaling cascade and its physiological consequences.

    Evidence Muscle-specific AdipoR1 conditional KO with Ca²⁺ measurements, SIRT1/PGC-1α acetylation assays, mitochondrial content, and exercise testing

    PMID:20357764

    Open questions at the time
    • Ion channel mediating Ca²⁺ influx not identified
    • Whether this cascade operates identically in human muscle unknown
  5. 2010 High

    Identification of ERp46 as a physical interactor that retains ADIPOR1 intracellularly through binding to its N-terminal cytoplasmic domain revealed the first post-translational mechanism controlling receptor surface expression.

    Evidence Reciprocal Co-IP with MS, GST pull-down with truncation mapping, siRNA knockdown showing increased surface ADIPOR1 and enhanced AMPK signaling

    PMID:20074551

    Open questions at the time
    • Whether ERp46 acts as a chaperone or quality-control factor was not distinguished
    • Regulation of the ERp46–ADIPOR1 interaction under physiological stimuli not explored
  6. 2011 Medium

    Multiple studies established ADIPOR1 as an upstream activator of NF-κB in both pro-inflammatory (endothelial COX-2, chondrocyte MMP-3) and anti-inflammatory (macrophage foam cell suppression via APPL1) contexts, revealing cell-type-dependent pathway utilization.

    Evidence AdipoR1 siRNA in endothelial cells, chondrocytes, and macrophages with NF-κB, COX-2, MMP-3, and cytokine readouts; APPL1 shRNA epistasis

    PMID:21321996 PMID:21900123 PMID:22227293

    Open questions at the time
    • Mechanism determining whether ADIPOR1–NF-κB signaling is pro- or anti-inflammatory in a given cell type unknown
    • APPL1 binding site on ADIPOR1 not mapped
  7. 2013 High

    The finding that miR-221 and PTB cooperatively repress ADIPOR1 translation via its 3′UTR — both being upregulated in obesity — provided a molecular explanation for reduced ADIPOR1 protein in metabolic disease.

    Evidence RNA-IP, luciferase 3′UTR reporters, gain- and loss-of-function in multiple cell types and obese mouse models

    PMID:24130336

    Open questions at the time
    • Whether therapeutic targeting of miR-221/PTB restores ADIPOR1 levels and metabolic function in vivo not tested
    • Other post-transcriptional regulators not surveyed
  8. 2015 Medium

    Demonstration that ADIPOR1 forms functional signaling complexes with Caveolin-1 (endothelial) and Caveolin-3 (cardiomyocyte) — required for anti-oxidative, anti-inflammatory, and cardioprotective actions — established caveolae as critical signaling platforms for ADIPOR1.

    Evidence Co-IP, Cav1/Cav3 knockdown/overexpression and mutant Cav1 knock-in with eNOS/AMPK/STAT3 readouts; APN-KO ischemia/reperfusion model

    PMID:26453924 PMID:26718505

    Open questions at the time
    • Direct structural basis for ADIPOR1–caveolin interaction not determined
    • Whether caveolar localization affects ceramidase activity unknown
  9. 2016 High

    Identification of ADIPOR1 mutations (p.Y310C and c.31delC) as causes of retinitis pigmentosa, validated by in vitro protein misfolding and zebrafish rescue experiments, established ADIPOR1 as a retinal disease gene.

    Evidence Exome sequencing of RP families; in vitro folding/localization of mutant protein; zebrafish morpholino knockdown rescued by WT but not mutant ADIPOR1; Adipor1-null mouse retinal dystrophy

    PMID:26662040 PMID:27655171

    Open questions at the time
    • Full allelic spectrum of ADIPOR1-associated retinal disease not defined
    • Whether ceramidase loss alone explains photoreceptor death from these mutations not determined at this point
  10. 2018 High

    Cell-type-specific conditional knockouts in serotonergic and dopaminergic neurons demonstrated that ADIPOR1 is a non-redundant regulator of neurotransmitter synthesis and neuronal excitability, with loss producing depression- and anxiety-related behaviors.

    Evidence Conditional KO in 5-HT (Pet1-Cre) and DA (DAT-Cre) neurons; TPH2/SERT expression; electrophysiology of VTA DA neurons; behavioral testing with pharmacological dissection

    PMID:29988086 PMID:31980728

    Open questions at the time
    • Downstream signaling pathway from ADIPOR1 to TPH2 transcription not mapped
    • Whether adiponectin or a different ligand activates neuronal ADIPOR1 in vivo not established
  11. 2019 High

    Demonstrating that ADIPOR1/R2 double-knockout cells exhibit membrane rigidification upon saturated fatty acid challenge — independent of adiponectin — revealed a ligand-independent membrane homeostasis function for the receptor.

    Evidence ADIPOR1/R2 DKO in HUVECs and multiple cell lines; FRAP, Laurdan dye, phospholipid mass spectrometry under palmitate challenge

    PMID:30890562

    Open questions at the time
    • Relative contributions of ADIPOR1 vs. ADIPOR2 to membrane fluidity maintenance not separated
    • Whether this function requires ceramidase activity specifically not tested
  12. 2020 High

    Crystallographic resolution of closed-to-open conformational transitions in ADIPOR1 (helices IV and V shifting 4–11 Å) provided the first structural framework for understanding how receptor activation propagates signal to the intracellular domain.

    Evidence X-ray crystallography of D208A variant and reanalysis of wild-type diffraction data revealing 44:56 closed:open equilibrium

    PMID:32796916

    Open questions at the time
    • Ligand-bound structure not captured; whether adiponectin binding shifts the conformational equilibrium is inferred but not proven
    • How conformational change couples to AMPK activation or ceramidase activity not established
  13. 2022 High

    Establishing that ADIPOR1 possesses intrinsic ceramidase activity — whose loss causes ceramide accumulation and photoreceptor degeneration rescuable by ceramide synthesis inhibitors — unified the retinal disease phenotype with a specific enzymatic mechanism.

    Evidence ADIPOR1-KO mice; retinal ceramide quantification by lipidomics; ERG and primary visual cortex electrophysiology; pharmacological rescue with desipramine/L-cycloserine

    PMID:35015730

    Open questions at the time
    • Kinetic parameters and substrate specificity of ADIPOR1 ceramidase activity not characterized biochemically with purified protein
    • Whether ceramidase activity is regulated by adiponectin binding or conformational state not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how adiponectin binding couples to the closed-to-open conformational switch and ceramidase activation; the identity of the Ca²⁺ channel mediating ADIPOR1-dependent Ca²⁺ influx; and whether neuronal ADIPOR1 functions are adiponectin-dependent or involve alternative ligands or ligand-independent mechanisms.
  • No ligand-bound ADIPOR1 structure available
  • Ca²⁺ channel identity unknown
  • Neuronal ligand identity uncertain
  • Ceramidase kinetics with purified protein not reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 3 GO:0060089 molecular transducer activity 3 GO:0016787 hydrolase activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-5357801 Programmed Cell Death 3 R-HSA-112316 Neuronal System 2 R-HSA-168256 Immune System 2
Partners
ADIPOQADIPOR2APPL1CAV1CAV3ERP46LKB1
Complex memberships
AdipoR1/Caveolin-1 complexAdipoR1/Caveolin-3 complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 Targeted disruption of AdipoR1 in mice abrogated adiponectin-induced AMPK activation, while simultaneous disruption of AdipoR1 and AdipoR2 abolished adiponectin binding entirely, demonstrating that AdipoR1 and AdipoR2 are the predominant in vivo receptors for adiponectin and that AdipoR1 specifically mediates AMPK activation. Adenovirus-mediated overexpression in Lepr(-/-) mice; targeted gene disruption (knockout mice); in vivo metabolic phenotyping Nature medicine High 17268472
2010 AdipoR1 mediates adiponectin-induced extracellular Ca2+ influx in myocytes, which activates CaMKKβ, AMPK, and SIRT1, leading to increased PGC-1α expression, decreased PGC-1α acetylation, and increased mitochondrial biogenesis; muscle-specific disruption of AdipoR1 suppressed all of these downstream events and caused insulin resistance and decreased exercise endurance. Muscle-specific AdipoR1 knockout mice; intracellular Ca2+ measurements; AMPK/SIRT1/PGC-1α western blotting; mitochondrial content assays; exercise endurance testing Nature High 20357764
2009 AdipoR1 signals through LKB1 and AMPK to suppress hepatic SREBP1c expression, thereby regulating fatty acid synthesis; deletion of LKB1 abolished the adiponectin-mediated suppression of SREBP1c. siRNA knockdown of AdipoR1; LKB1-deleted hepatocytes; SREBP1c expression by western blot/qPCR in db/db mice and cultured hepatocytes Biochemical and biophysical research communications Medium 19254698
2008 AdipoR1, but not AdipoR2, mediates adiponectin-induced anorexigenic signaling in the hypothalamus, activating IRS1/2, ERK, Akt, FOXO1, JAK2, and STAT3 to reduce food intake; inhibition of AdipoR1 completely reversed these effects. ICV adiponectin administration; AdipoR1/R2 receptor inhibition; phosphorylation of downstream signaling molecules by western blot; food intake measurement FEBS letters Medium 18394428
2010 ERp46 (endoplasmic reticulum protein 46) interacts specifically with AdipoR1 (but not AdipoR2) through the cytoplasmic N-terminal residues (1-70) of AdipoR1; ERp46 knockdown increased AdipoR1 surface expression and enhanced adiponectin-stimulated AMPK phosphorylation while reducing p38MAPK phosphorylation. Co-immunoprecipitation followed by mass spectrometry; GST-fusion protein pull-down with truncation constructs; subcellular fractionation; indirect immunofluorescence; siRNA knockdown; AMPK/p38MAPK phosphorylation assays Biochemical and biophysical research communications High 20074551
2011 AdipoR1 mediates adiponectin signaling to suppress TNFα and MCP-1 expression and inhibit macrophage foam cell transformation, while APPL1 knockdown abrogated adiponectin's ability to inhibit lipid accumulation, SR-AI expression, NF-κB, and Akt phosphorylation in foam cells. Overexpression and siRNA knockdown of AdipoR1/AdipoR2; lentiviral shRNA knockdown of APPL1; oxLDL-induced foam cell transformation; cytokine gene expression; lipid accumulation assays Atherosclerosis Medium 22227293
2008 In renal distal tubules, adiponectin acts through luminal AdipoR1 (but not AdipoR2, which was not detected) to activate AMPK, leading to inhibition of glycogen synthase; in diabetic rats this regulation is disrupted, correlating with glycogen accumulation. Western blot of isolated distal tubules; immunohistochemistry; in vitro AICAR and globular adiponectin stimulation; AMPK and glycogen synthase activity assays in normal vs. STZ-diabetic rats American journal of physiology. Renal physiology Medium 18256313
2011 Adiponectin increases MMP-3 expression in chondrocytes through AdipoR1 (not AdipoR2) by activating AMPK and p38, which leads to NF-κB activation on the MMP-3 promoter. AdipoR1/AdipoR2 siRNA knockdown; AMPK inhibitors (araA, compound C); p38 inhibitor (SB203580); NF-κB inhibitor; qPCR, western blot, and ELISA for MMP-3 Journal of cellular biochemistry Medium 21321996
2011 Globular adiponectin protects cardiomyocytes (H9c2) from hypoxia/reoxygenation-induced apoptosis via AdipoR1/APPL1 signaling, reducing ROS production and caspase-3 activation; siRNA knockdown of either AdipoR1 or APPL1 abolished these protective effects. siRNA knockdown of AdipoR1 and APPL1; TUNEL labeling; annexin V; cytochrome c release; caspase-3 activity; ROS measurement PloS one Medium 21552570
2009 Adiponectin inhibits LPS-induced adventitial fibroblast migration and transformation to myofibroblasts via the AdipoR1–AMPK–iNOS pathway; siRNA knockdown of AdipoR1 or AMPK reversed adiponectin's inhibitory effects on NO/ONOO- production and fibroblast migration. AdipoR1 siRNA; AMPK siRNA; AMPK inhibitor; MTT, migration/scratch-wound assays; immunocytochemistry; RT-PCR; western blot; NO/ONOO- assays; adenovirus-adiponectin in ApoE-/- mice Molecular endocrinology (Baltimore, Md.) Medium 19889816
2011 Globular adiponectin activates NF-κB and induces COX-2 overexpression in human aortic endothelial cells through AdipoR1; AdipoR1 siRNA abrogated NF-κB activation and COX-2 expression, while p38MAPK/VCAM-1 activation was AdipoR1-independent. AdipoR1 siRNA; NF-κB activation assay; COX-2/VCAM-1 expression by western blot; monocyte adhesion assay; prostacyclin ELISA American journal of physiology. Endocrinology and metabolism Medium 21900123
2012 Overexpression of AdipoR1 in rat skeletal muscle increased glucose uptake, glycogen accumulation, and AMPK/acetyl-CoA carboxylase phosphorylation, and reduced levels of specific ceramide species and ceramide synthetic enzyme mRNAs, demonstrating that enhanced AdipoR1 signaling is sufficient to improve local insulin sensitivity. In vivo electrotransfer-mediated AdipoR1 overexpression; hyperinsulinemic-euglycemic clamp; glucose uptake measurement; sphingolipid mass spectrometry; western blot of signaling molecules Endocrinology Medium 22989629
2013 miR-221 and the RNA-binding protein PTB cooperatively bind the AdipoR1 3'UTR and inhibit AdipoR1 translation; depletion of PTB or miR-221 increased AdipoR1 protein synthesis, while overexpression decreased it. Both PTB and miR-221 are upregulated in obesity, providing a mechanism for reduced AdipoR1 protein in obese animals. RNA-immunoprecipitation; luciferase reporter assays with 3'UTR constructs; siRNA depletion and overexpression of PTB and miR-221; AdipoR1 protein quantification in muscle and liver cells; mouse models of obesity Diabetes High 24130336
2014 AdipoR1 deficiency in mice led to severe metabolic dysfunction (diet-induced obesity model), while AdipoR2 deficiency was protective from metabolic perturbations; conversely, AdipoR2 (not AdipoR1) was required for ischemia-induced revascularization and for adiponectin's pro-revascularization effects, revealing divergent in vivo roles. AdipoR1-/- and AdipoR2-/- mice; hind limb ischemia model; blood flow measurement; diet-induced obesity; metabolic phenotyping The Journal of biological chemistry High 24742672
2015 AdipoR1 (but not AdipoR2) depletion abolished the protective effects of the AdipoR1 agonist GTDF on osteoblasts, and AdipoR1 agonism restored osteopenia in diabetic mice by upregulating PGC-1α in osteoblasts; AdipoR1 deficiency in bone is a key mediator of diabetes-associated skeletal pathology. AdipoR1 siRNA; AdipoR1 agonist GTDF treatment; PGC-1α expression; db/db mouse model; bone mass measurements (µCT); osteoblast apoptosis assays Diabetes Medium 25633418
2015 IPo (ischemic postconditioning) activates mitochondrial STAT3 through APN/AdipoR1/Caveolin-3 pathway to confer cardioprotection; specific AdipoR1 gene knockdown or Cav3 disruption abolished hypoxic postconditioning-induced protection, demonstrating that AdipoR1 forms a functional complex with Cav3 to transduce adiponectin cardioprotective signaling. AdipoR1 siRNA knockdown; Cav3 disruption; APN knockout mice; coronary occlusion/reperfusion model; mitochondrial STAT3 activation; mitochondrial function assays 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, and morpholino knockdown of adipor1 in zebrafish specifically reduced rod photoreceptor numbers, a phenotype partially rescued by wild-type but not mutant human ADIPOR1 mRNA. Exome sequencing; in vitro protein folding/localization assays; zebrafish morpholino knockdown; morphant rescue with wild-type vs. mutant ADIPOR1 mRNA Human genetics High 27655171
2016 ADIPOR1 is mutated (frameshift c.31delC) in a syndromic retinitis pigmentosa case, and ADIPOR1 protein is expressed in the retina; Adipor1-null mice exhibit retinal dystrophy, supporting ADIPOR1 as a disease-causing gene for syndromic RP. Whole-exome sequencing; immunohistochemistry of retinal tissue; Adipor1-null mouse phenotype Human mutation Medium 26662040
2018 AdipoR1 is expressed in dorsal raphe nucleus serotonin (5-HT) neurons; selective deletion of AdipoR1 in 5-HT neurons decreased TPH2 expression and 5-HT immunoreactivity, upregulated SERT, and induced anhedonia and behavioral despair in a sex-dependent manner, establishing AdipoR1 as a regulator of serotonergic neurotransmission and depression-related behavior. Conditional (cell-type-specific) AdipoR1 knockout in 5-HT neurons; immunofluorescence for TPH2/SERT; behavioral tests (sucrose preference, saccharin preference, FST); fluoxetine vs. desipramine pharmacological dissection Molecular psychiatry High 31980728
2018 AdipoR1 is expressed on VTA dopamine neurons; intra-VTA infusion of adiponectin decreases basal dopamine neuron firing and reverses stress-induced dopamine activity and anxiety, and these effects are abolished in mice lacking AdipoR1 specifically in dopamine neurons. Conditional AdipoR1 knockout in dopamine neurons; electrophysiology (population activity, firing rate); intra-VTA infusion; anxiety behavioral tests; adiponectin haploinsufficiency Molecular psychiatry High 29988086
2018 Adiponectin attenuates neuronal apoptosis after neonatal hypoxia-ischemia via sequential activation of AdipoR1→APPL1→LKB1→AMPK; siRNA knockdown of any component (AdipoR1, APPL1, or LKB1) abolished the anti-apoptotic effects of recombinant adiponectin. AdipoR1, APPL1, and LKB1 siRNA (intracerebroventricular); intranasal rh-Adiponectin administration; brain infarct measurement; TUNEL; western blot of pathway components; neurological function testing Neuropharmacology Medium 29486166
2019 AdipoR1 and AdipoR2 are essential for maintaining membrane phospholipid unsaturation and membrane fluidity in most human cell types, independently of adiponectin; loss of AdipoRs causes membrane rigidification when cells are challenged with saturated fatty acids, demonstrating a ligand-independent membrane homeostasis function. AdipoR1/AdipoR2 double knockout; FRAP; Laurdan dye generalized polarization; phospholipid fatty acid composition by mass spectrometry; palmitate challenge; primary HUVECs and multiple human cell lines Journal of lipid research High 30890562
2019 AdipoR1 knockdown in BV2 microglia abolished adiponectin's ability to suppress AβO-induced TNFα and IL-1β release and AMPK phosphorylation, and prevented NF-κB nuclear translocation, placing AdipoR1 upstream of AMPK→NF-κB in the anti-neuroinflammatory pathway. AdipoR1/AdipoR2 siRNA in BV2 cells; AMPK inhibitor (Compound C); cytokine ELISA; AMPK phosphorylation by western blot; NF-κB nuclear translocation; APN-/-5xFAD mice neuroinflammation assessment Journal of neuroinflammation Medium 31128596
2020 Crystal structure of a D208A variant AdipoR1 revealed both 'closed' and 'open' conformations, with helices IV and V shifting ~4-11 Å at intracellular ends between states; reanalysis of wild-type AdipoR1 diffraction data also showed a 44:56 mixture of closed and open forms, suggesting conformational switching is relevant to receptor function. X-ray crystallography of D208A AdipoR1 variant; structural comparison with wild-type; reanalysis of wild-type diffraction data Communications biology High 32796916
2022 AdipoR1 possesses intrinsic ceramidase activity; AdipoR1 knockout in mice causes ceramide accumulation in the retina leading to photoreceptor degeneration, and pharmacological inhibition of ceramide generation (desipramine/L-cycloserine) rescued photoreceptor survival and improved visual function in AdipoR1-/- mice. AdipoR1-/- mice; single-cell RNA-seq; ceramide quantification by lipidomics; ERG; pharmacological rescue with desipramine/L-cycloserine; primary visual cortex electrophysiology JCI insight High 35015730
2021 ADIPOR1 deficiency in mice suppresses retinal ELOVL2 expression and reduces docosahexaenoic acid (DHA) levels in photoreceptor outer segment membranes prior to cell death, and this causal relationship between ADIPOR1 and ELOVL2 repression was confirmed in vitro, establishing ADIPOR1 as required for DHA supply to photoreceptors. Adipor1 KO mice; ERG; lipid composition analysis; gene expression (RT-qPCR, microarray); in vitro ADIPOR1 depletion confirming ELOVL2 regulation; electron microscopy of outer segments Cell death & disease Medium 33963174
2018 Post-developmental conditional knockout of AdipoR1 specifically in photoreceptors or the RPE caused decreased retinal protein expression and visual dysfunction, and loss of AdipoR1 in the RPE alone (as in the Mfrprd6 mouse) is sufficient to drive retinal degeneration. Conditional (photoreceptor- and RPE-specific) AdipoR1 knockout; ERG; immunohistochemistry; Mfrprd6 mouse ADIPOR1 expression analysis Scientific reports High 30254279
2020 AdipoR1 is required for adiponectin receptor agonist (AdipoRon) signaling to AMPK in the context of Alzheimer's disease; both AdipoR1 silencing and AMPK inhibition (compound C) reversed AdipoRon-mediated neural stem cell proliferation and cognitive improvement in APP/PS1 mice. AdipoR1 siRNA; AMPK inhibitor; in vivo APP/PS1 transgenic mice; Morris water maze; BrdU/Ki67 staining for NSC proliferation; BACE1/Aβ quantification Experimental neurology Medium 32070713
2015 High glucose/high lipid conditions dissociate the AdipoR1/Caveolin-1 (Cav1) signaling complex in endothelial cells by reducing Cav1 expression; Cav1 knockdown impaired adiponectin's anti-oxidative and anti-inflammatory actions, while Cav1 overexpression preserved APN signaling. A mutated Cav1 scaffolding domain restored caveolae structure but not APN signaling, demonstrating the AdipoR1/Cav1 interaction is critical for adiponectin vascular signaling. Co-immunoprecipitation; Cav1 siRNA and overexpression; mutant Cav1 knock-in; eNOS/AMPK/Akt phosphorylation; NO measurement; diabetic vascular tissue analysis Free radical biology & medicine Medium 26453924
2020 AdipoR1 conditional knockout in CD4+ T cells inhibited Th17 cell differentiation by reducing HIF-1α expression and glycolysis, and AdipoR1-deficient mice showed ameliorated joint inflammation in antigen-induced arthritis, identifying AdipoR1 as a regulator of Th17 differentiation via HIF-1α-dependent metabolic reprogramming. T cell lineage AdipoR1 conditional KO; RNA-seq; Th17 differentiation assay in vitro; antigen-induced arthritis mouse model; HIF-1α/glycolysis metabolic measurements Frontiers in immunology Medium 32973810
2022 AdipoR1 directly targets and stabilizes Nrf2 protein in hepatocellular carcinoma cells after ionizing radiation; AdipoR1 knockdown suppressed Nrf2 and its target xCT, increasing ferroptosis after radiation, while rescue of Nrf2 or xCT reversed this effect, establishing an AdipoR1-Nrf2-xCT axis in radiation-induced ferroptosis. AdipoR1 siRNA knockdown; Nrf2/xCT western blot; ChIP for Nrf2 on xCT promoter; ferroptosis/cell death assays; erastin treatment; Nrf2/xCT rescue overexpression Oxidative medicine and cellular longevity Medium 35733794
2022 AdipoR1 ubiquitination is induced by LPS+ATP in vitro, and Schisandrin A directly targets AdipoR1 protein to reduce this ubiquitination and activate AdipoR1/AMPK signaling, suppressing ferroptosis and NLRP3-mediated pyroptosis in diabetic nephropathy models. Direct binding assay; ubiquitination assay; AdipoR1/AMPK/TXNIP/NLRP3 pathway western blot; in vivo STZ/high-fat diabetic model Oxidative medicine and cellular longevity Low 35996380

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 1111 17268472
2010 Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1. Nature 834 20357764
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 171 27001618
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 141 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 116 33199780
2007 Adiponectin inhibits the growth and peritoneal metastasis of gastric cancer through its specific membrane receptors AdipoR1 and AdipoR2. Cancer science 114 17459059
2006 Expression of adiponectin and its receptors (AdipoR1 and AdipoR2) in chicken ovary: potential role in ovarian steroidogenesis. Domestic animal endocrinology 111 17010558
2008 Variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes and colorectal cancer risk. JAMA 109 18827209
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 93 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 87 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 74 27897419
2004 Adiponectin receptor 1 gene (ADIPOR1) as a candidate for type 2 diabetes and insulin resistance. Diabetes 74 15277397
2011 Globular adiponectin, acting via AdipoR1/APPL1, protects H9c2 cells from hypoxia/reoxygenation-induced apoptosis. PloS one 70 21552570
2009 Role of adiponectin receptors, AdipoR1 and AdipoR2, in the steroidogenesis of the human granulosa tumor cell line, KGN. Human reproduction (Oxford, England) 70 19671624
2009 Gene-nutrient interactions in the metabolic syndrome: single nucleotide polymorphisms in ADIPOQ and ADIPOR1 interact with plasma saturated fatty acids to modulate insulin resistance. The American journal of clinical nutrition 70 20032495
2020 Modulation of depression-related behaviors by adiponectin AdipoR1 receptors in 5-HT neurons. Molecular psychiatry 66 31980728
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
2018 Adiponectin modulates ventral tegmental area dopamine neuron activity and anxiety-related behavior through AdipoR1. Molecular psychiatry 63 29988086
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
2006 Genetic analysis of ADIPOR1 and ADIPOR2 candidate polymorphisms for type 2 diabetes in the Caucasian population. Diabetes 62 16505255
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
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 59 38361125
2012 Overexpression of the adiponectin receptor AdipoR1 in rat skeletal muscle amplifies local insulin sensitivity. Endocrinology 58 22989629
2009 Adiponectin inhibits lipopolysaccharide-induced adventitial fibroblast migration and transition to myofibroblasts via AdipoR1-AMPK-iNOS pathway. Molecular endocrinology (Baltimore, Md.) 57 19889816
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 56 29022894
2010 ERp46 binds to AdipoR1, but not AdipoR2, and modulates adiponectin signalling. Biochemical and biophysical research communications 56 20074551
2017 CTRP6 Regulates Porcine Adipocyte Proliferation and Differentiation by the AdipoR1/MAPK Signaling Pathway. Journal of agricultural and food chemistry 55 28535682
2020 Tectorigenin attenuates diabetic nephropathy by improving vascular endothelium dysfunction through activating AdipoR1/2 pathway. Pharmacological research 54 32014572
2020 AdipoRon improves cognitive dysfunction of Alzheimer's disease and rescues impaired neural stem cell proliferation through AdipoR1/AMPK pathway. Experimental neurology 54 32070713
2017 Globular Adiponectin Limits Microglia Pro-Inflammatory Phenotype through an AdipoR1/NF-κB Signaling Pathway. Frontiers in cellular neuroscience 52 29184485
2015 Pathophysiological Mechanism of Bone Loss in Type 2 Diabetes Involves Inverse Regulation of Osteoblast Function by PGC-1α and Skeletal Muscle Atrogenes: AdipoR1 as a Potential Target for Reversing Diabetes-Induced Osteopenia. Diabetes 52 25633418
2019 Resveratrol regulates skeletal muscle fibers switching through the AdipoR1-AMPK-PGC-1α pathway. Food & function 50 31095141
2020 Genistein inhibits high fat diet-induced obesity through miR-222 by targeting BTG2 and adipor1. Food & function 49 32129363
2009 No association between polymorphisms in LEP, LEPR, ADIPOQ, ADIPOR1, or ADIPOR2 and postmenopausal breast cancer risk. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 49 19723917
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 44 31176703
2016 A mutation in ADIPOR1 causes nonsyndromic autosomal dominant retinitis pigmentosa. Human genetics 44 27655171
2016 CTRP9 induces mitochondrial biogenesis and protects high glucose-induced endothelial oxidative damage via AdipoR1 -SIRT1- PGC-1α activation. Biochemical and biophysical research communications 43 27349872
2023 Neuroprotective effects of osmotin in Parkinson's disease-associated pathology via the AdipoR1/MAPK/AMPK/mTOR signaling pathways. Journal of biomedical science 41 37568205
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
2016 ADIPOR1 Is Mutated in Syndromic Retinitis Pigmentosa. Human mutation 40 26662040
2006 Expression of the adiponectin receptors AdipoR1 and AdipoR2 in lean rats and in obese Zucker rats. Metabolism: clinical and experimental 39 16483885
2018 ADIPOR1 is essential for vision and its RPE expression is lost in the Mfrprd6 mouse. Scientific reports 38 30254279
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
2012 Adiponectin receptor 1 gene (ADIPOR1) variant is associated with advanced age-related macular degeneration in Finnish population. Neuroscience letters 38 22387454
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 37 35720361
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
2014 Orally active osteoanabolic agent GTDF binds to adiponectin receptors, with a preference for AdipoR1, induces adiponectin-associated signaling, and improves metabolic health in a rodent model of diabetes. Diabetes 36 24848063
2008 The association of SNPs in ADIPOQ, ADIPOR1, and ADIPOR2 with insulin sensitivity in a cohort of adolescents and their parents. Human genetics 36 19037660
2006 Common haplotypes at the adiponectin receptor 1 (ADIPOR1) locus are associated with increased risk of coronary artery disease in type 2 diabetes. Diabetes 36 17003341
2013 Expression of adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) in the porcine pituitary during the oestrous cycle. Reproductive biology and endocrinology : RB&E 35 23497348
2021 Adiponectin/AdipoR1 Axis Promotes IL-10 Release by Human Regulatory T Cells. Frontiers in immunology 34 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 34 33096235
2019 AdipoRon Protects Against Secondary Brain Injury After Intracerebral Hemorrhage via Alleviating Mitochondrial Dysfunction: Possible Involvement of AdipoR1-AMPK-PGC1α Pathway. Neurochemical research 33 30982205
2019 Adiponectin Protects Against Cerebral Ischemic Injury Through AdipoR1/AMPK Pathways. Frontiers in pharmacology 33 31231213
2022 Inhibition of ceramide accumulation in AdipoR1-/- mice increases photoreceptor survival and improves vision. JCI insight 32 35015730
2017 Osmotin Protects H9c2 Cells from Simulated Ischemia-Reperfusion Injury through AdipoR1/PI3K/AKT Signaling Pathway. Frontiers in physiology 32 28993734
2021 ADIPOR1 deficiency-induced suppression of retinal ELOVL2 and docosahexaenoic acid levels during photoreceptor degeneration and visual loss. Cell death & disease 31 33963174
2014 Expression of adiponectin and adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) in the porcine uterus during the oestrous cycle. Animal reproduction science 31 24598213
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
2017 The role of AdipoR1 and AdipoR2 in liver fibrosis. Biochimica et biophysica acta. Molecular basis of disease 29 29237572
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 28 33500643
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
2009 The expression of adiponectin receptors Adipo-R1 and Adipo-R2 is associated with an intestinal histotype and longer survival in gastric carcinoma. Journal of clinical pathology 28 19638541
2020 Critical Role of AdipoR1 in Regulating Th17 Cell Differentiation Through Modulation of HIF-1α-Dependent Glycolysis. Frontiers in immunology 26 32973810
2022 Aerobic Exercise Alleviates Abnormal Autophagy in Brain Cells of APP/PS1 Mice by Upregulating AdipoR1 Levels. International journal of molecular sciences 25 36077318
2021 CTRP9 Enhances Efferocytosis in Macrophages via MAPK/Drp1-Mediated Mitochondrial Fission and AdipoR1-Induced Immunometabolism. Journal of inflammation research 25 33790616
2017 MiR-221 mediates the epithelial-mesenchymal transition of hepatocellular carcinoma by targeting AdipoR1. International journal of biological macromolecules 25 28539268
2022 AdipoR1 Regulates Ionizing Radiation-Induced Ferroptosis in HCC cells through Nrf2/xCT Pathway. Oxidative medicine and cellular longevity 24 35733794
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
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) 24 34066039
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
2014 Ginsenoside Rb1 stimulates adiponectin signaling in C2C12 muscle cells through up-regulation of AdipoR1 and AdipoR2 proteins. Pharmaceutical biology 23 25311947
2019 Administration of rCTRP9 Attenuates Neuronal Apoptosis Through AdipoR1/PI3K/Akt Signaling Pathway after ICH in Mice. Cell transplantation 21 30642187
2015 High glucose/High Lipids impair vascular adiponectin function via inhibition of caveolin-1/AdipoR1 signalsome formation. Free radical biology & medicine 21 26453924
2020 Human adiponectin receptor AdipoR1 assumes closed and open structures. Communications biology 20 32796916
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
2020 LncRNA loc105377478 promotes NPs-Nd2O3-induced inflammation in human bronchial epithelial cells through the ADIPOR1/NF-κB axis. Ecotoxicology and environmental safety 19 33396129
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 Activation of AdipoR1 with rCTRP9 Preserves BBB Integrity through the APPL1/AMPK/Nrf2 Signaling Pathway in ICH Mice. Oxidative medicine and cellular longevity 17 34925690
2018 miR-320 mediates diabetes amelioration after duodenal-jejunal bypass via targeting adipoR1. Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery 17 29960867
2017 AdipoR1-mediated miR-3908 inhibits glioblastoma tumorigenicity through downregulation of STAT2 associated with the AMPK/SIRT1 pathway. Oncology reports 17 28440504
2009 Adiponectin induced placental cell apoptosis could be mediated via the ADIPOR1-receptor in pre-eclampsia with IUGR. Journal of perinatal medicine 17 19196212