Affinage

ADIPOR2

Adiponectin receptor protein 2 · UniProt Q86V24

Length
386 aa
Mass
43.9 kDa
Annotated
2026-04-28
100 papers in source corpus 34 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADIPOR2 encodes an evolutionarily conserved seven-transmembrane receptor that functions as a master regulator of membrane lipid homeostasis, sensing membrane rigidification caused by saturated fatty acids and restoring fluidity by promoting fatty acid desaturation, elongation, and incorporation of polyunsaturated fatty acids into phospholipids (PMID:28886012, PMID:33444761, PMID:37164154, PMID:38485951). This membrane-fluidizing function operates in part through physical recruitment of the fatty acid elongation dehydratase HACD3 and the acyl-CoA synthetase ACSL4, and through transcriptional upregulation of desaturases and ELOVL2, and is subject to autoregulatory feedback via the ER ubiquitin ligase RNF145, which degrades AdipoR2 when membranes are unsaturated-rich and is itself degraded when membranes become saturated (PMID:37164154, PMID:35993436, PMID:38485951). As a receptor for adiponectin (and other C1q-family ligands), AdipoR2 signals through AMPK, PPARα, ERK1/2, and a Ca²⁺–CaM–CaMKII–NOS3 complex to regulate hepatic fatty acid oxidation, anti-fibrotic responses in stellate cells, revascularization, Th17 suppression, and neuronal excitability in the dentate gyrus (PMID:17268472, PMID:18666257, PMID:29237572, PMID:27137743, PMID:39681560). Loss of AdipoR2 in mice causes tissue-specific accumulation of saturated fatty acids with consequent membrane stiffening, leading to meiotic failure in testes, brain lipid remodeling with behavioral abnormalities, and exacerbated metabolic and inflammatory pathology (PMID:38485951, PMID:38989587, PMID:17268472).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2006 High

    Establishing that adiponectin selectively downregulates AdipoR2 expression in adipose tissue revealed a ligand-dependent negative-feedback loop that distinguishes AdipoR2 from AdipoR1 at the transcriptional level.

    Evidence Transgenic adiponectin-overexpressing and adiponectin-null mice with qPCR and adipocyte culture

    PMID:16729974

    Open questions at the time
    • Mechanism of selective transcriptional repression not identified
    • Whether feedback operates in non-adipose tissues unknown
  2. 2007 High

    Knockout mice demonstrated that AdipoR2 is required for adiponectin-mediated PPARα activation in liver and that loss of both AdipoR1 and AdipoR2 abolishes all adiponectin actions, establishing these as the principal adiponectin receptors in vivo.

    Evidence AdipoR2 single and AdipoR1/R2 double KO mice with adenoviral rescue in Lepr⁻/⁻ liver; metabolic phenotyping

    PMID:17268472

    Open questions at the time
    • Receptor-specific downstream effectors not fully delineated
    • Relative contribution to non-hepatic tissues unclear
  3. 2008 High

    Bidirectional manipulation in liver and hepatocytes placed AdipoR2 upstream of PPARα-driven catalase expression and fatty acid oxidation, while parallel work showed AdipoR2 can signal through Src/Ras/ERK1/2 via the adaptor APPL1, broadening the signaling repertoire beyond AMPK/PPARα.

    Evidence Adenoviral KD/OE in MCD-diet mice and TGFβ-treated hepatocytes; siRNA/pharmacological inhibition in HEK293 cells

    PMID:18666257 PMID:18842004

    Open questions at the time
    • Direct physical interaction between AdipoR2 and Src not shown
    • Relative use of ERK vs PPARα pathways in different cell types not resolved
  4. 2010 High

    Receptor-specific knockdown in macrophages, stellate cells, and ischemia models established that AdipoR2 has non-redundant roles distinct from AdipoR1 — particularly in anti-inflammatory SR-AI suppression, anti-fibrotic signaling, and revascularization — while domain-swapping showed the N-terminal cytoplasmic tail controls surface expression and temporal signaling profiles.

    Evidence Lentiviral shRNA in THP-1 macrophages; chimeric/truncated receptor constructs with quantitative surface expression; AdipoR1/R2 KO mice in hindlimb ischemia

    PMID:20074551 PMID:22227293 PMID:23376713 PMID:24742672

    Open questions at the time
    • Structural basis for N-terminal gating of surface expression unknown
    • Whether AdipoR1/R2 heterodimers have distinct signaling outputs not tested
  5. 2013 High

    A forward genetic suppressor screen in C. elegans revealed that the AdipoR2 homolog PAQR-2 controls membrane fluidity by regulating fatty acid desaturation and phospholipid composition, shifting the conceptual framework from pure adiponectin signaling to membrane lipid homeostasis.

    Evidence C. elegans suppressor screen with epistasis analysis and fatty acid composition measurements

    PMID:24068966

    Open questions at the time
    • Whether the mammalian receptor has intrinsic enzymatic activity or acts as a scaffold was unresolved
    • Mechanism of fluidity sensing not yet identified
  6. 2015 High

    Crystal structures of AdipoR2 (2.4 Å) and AdipoR1 revealed a novel seven-transmembrane fold with an internal cavity containing bound lipids, providing the first structural framework for the receptor's lipid-related functions.

    Evidence Lipidic mesophase crystallography with anti-AdipoR1 Fv, SPR ligand binding, thermostability assays

    PMID:25575462

    Open questions at the time
    • Identity of bound lipids not fully characterized
    • No structure with adiponectin or agonist bound
  7. 2016 High

    BiFC and FRAP experiments in C. elegans established that PAQR-2 physically interacts with IGLR-2 at the plasma membrane to form a fluidity-sensing complex, while DG-specific AdipoR2 KO in mice showed the receptor is required for fear extinction and regulation of granule neuron excitability.

    Evidence BiFC for PAQR-2/IGLR-2 interaction, FRAP in C. elegans; DG-specific KO mice with fear conditioning and patch-clamp

    PMID:27082444 PMID:27137743

    Open questions at the time
    • Mammalian homolog of IGLR-2 not identified
    • Whether neuronal AdipoR2 functions involve membrane fluidity sensing not tested
  8. 2017 High

    Direct membrane fluidity measurements in both C. elegans and mammalian cells demonstrated that AdipoR2 is essential to counteract palmitate-induced rigidification, confirming evolutionary conservation of the membrane homeostasis function; muscle-specific OE in mice showed AdipoR2 preferentially activates PPARα/acox1 with systemic metabolic benefits.

    Evidence FRAP and Laurdan GP in AdipoR2-KD mammalian cells and paqr-2 mutant worms; electrotransfer OE in mouse tibialis anterior

    PMID:28145500 PMID:28886012

    Open questions at the time
    • Signal transduction between fluidity sensing and desaturase transcription not mapped
    • Whether muscle AdipoR2 acts via fluidity regulation or canonical signaling unclear
  9. 2018 High

    Tissue-specific rescue and mosaic analysis showed PAQR-2 acts cell-nonautonomously: expression in one tissue restores membrane fluidity organism-wide, a property conserved in human cells where AdipoR2-expressing cells normalize fluidity in neighboring AdipoR2-silenced cells.

    Evidence C. elegans tissue-specific rescue constructs with FRAP; HEK293 co-culture with SCD siRNA

    PMID:29997234

    Open questions at the time
    • Identity of the secreted or transferred lipid signal mediating non-cell-autonomous rescue unknown
    • Whether this operates in intact mammalian tissues not shown
  10. 2019 High

    AdipoR2 sustains desaturase expression and unsaturated fatty acid levels in membrane phospholipids even in the absence of adiponectin, establishing that the core membrane homeostasis function is ligand-independent; in C. elegans, PAQR-2 promotes ω-6 PUFA synthesis linked to autophagy and lifespan extension at low temperature.

    Evidence AdipoR1/R2 KD with FRAP, Laurdan GP, and MS lipidomics in adiponectin-free conditions; C. elegans fatty acid profiling and autophagy assays

    PMID:30890562 PMID:31197136

    Open questions at the time
    • How AdipoR2 activates desaturase transcription without adiponectin not mechanistically resolved
    • Whether autophagy link extends to mammalian cells unknown
  11. 2021 High

    Genome-wide screening in C. elegans confirmed PAQR-2/IGLR-2 as the sole essential pathway for SFA tolerance, FRET showed their interaction is regulated by membrane fluidity itself, and multi-omic analysis in human cells ranked AdipoR2 as the single most important factor for preventing SFA-induced membrane rigidification and transcriptomic collapse.

    Evidence Forward genetic screen, FRET-based interaction monitoring, transcriptomics and lipidomics in AdipoR2-KD HEK293/HUVEC

    PMID:33444759 PMID:33444761

    Open questions at the time
    • Direct biophysical mechanism by which membrane fluidity regulates PAQR-2/IGLR-2 interaction not resolved
    • Downstream transcription factor(s) mediating AdipoR2-dependent desaturase gene activation unidentified
  12. 2022 High

    Identification of RNF145 as an ER-resident E3 ligase that ubiquitinates and degrades AdipoR2 when membranes are unsaturated-rich — and is itself degraded when membranes become saturated — revealed an autoregulatory feedback loop controlling AdipoR2 protein levels in response to membrane lipid composition.

    Evidence Systematic proteomics of cells fed saturated vs unsaturated FAs, ubiquitination assays, RNF145 KO/KD, lipotoxicity assays

    PMID:35993436

    Open questions at the time
    • RNF145 ubiquitination sites on AdipoR2 not mapped
    • Whether RNF145 regulation operates in vivo not shown
  13. 2023 High

    Co-IP/MS in human cells and C. elegans identified HACD3 and ACSL4 as conserved AdipoR2 physical interactors that mediate fatty acid elongation and channeling of unsaturated fatty acids into phospholipids, providing the first direct link between the receptor and the lipid-remodeling enzymatic machinery.

    Evidence 13C-labeled fatty acid tracing, co-IP/MS of tagged AdipoR2/PAQR-2 in HEK293 and C. elegans

    PMID:37164154

    Open questions at the time
    • Whether AdipoR2 has intrinsic ceramidase/hydrolase activity that contributes to HACD3/ACSL4 regulation not resolved
    • Structural basis of AdipoR2–HACD3/ACSL4 interaction unknown
  14. 2024 High

    AdipoR2 KO in mouse testes demonstrated that AdipoR2 promotes ELOVL2 expression to synthesize VLC-PUFAs essential for meiotic membrane integrity, telomere distribution, and homologous recombination; in brain, KO causes saturated FA excess with enlarged cerebrum and behavioral abnormalities; a novel AdipoR2–CaM–CaMKII–NOS3 signaling complex was identified through which AdipoR2 agonists drive Ca²⁺-dependent NO production for liver protection.

    Evidence AdipoR2 KO mice with testes lipidomics, meiotic spreads, EM; brain lipidomics/behavior; site-directed mutagenesis (R335, Y274), co-IP for complex, Ca²⁺ imaging, ALF model

    PMID:38485951 PMID:38989587 PMID:39681560

    Open questions at the time
    • How AdipoR2 regulates ELOVL2 transcription mechanistically not defined
    • Whether Ca²⁺/CaMKII signaling intersects with the membrane fluidity pathway is untested
    • Brain phenotype not yet linked to specific neuronal membrane composition changes at single-cell resolution

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include: (1) the identity of the mammalian IGLR-2 homolog that may partner with AdipoR2 for fluidity sensing; (2) whether AdipoR2 possesses intrinsic ceramidase or hydrolase activity in vivo and how this relates to its scaffold/receptor functions; (3) the transcription factor(s) downstream of AdipoR2 that activate desaturase and elongase gene expression; and (4) the structural basis of adiponectin or agonist binding to AdipoR2 in a full-length context.
  • No full-length AdipoR2 structure with ligand
  • Mammalian IGLR-2 counterpart unidentified
  • Intrinsic enzymatic activity debated but not definitively demonstrated in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0060089 molecular transducer activity 4 GO:0140299 molecular sensor activity 3 GO:0008289 lipid binding 2
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1430728 Metabolism 7 R-HSA-162582 Signal Transduction 6 R-HSA-1474165 Reproduction 1 R-HSA-168256 Immune System 1
Partners
ACSL4ADIPOQADIPOR1APPL1ELOVL2HACD3IGLR-2RNF145
Complex memberships
AdipoR2-CaM-CaMKII-NOS3

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 Targeted disruption of AdipoR2 in mice abrogates adiponectin binding and results in decreased PPAR-α signaling activity, increased tissue triglyceride content, inflammation, oxidative stress, insulin resistance, and glucose intolerance; simultaneous disruption of both AdipoR1 and AdipoR2 abolishes all adiponectin binding and actions in vivo. Targeted gene disruption (knockout mice), adenovirus-mediated receptor re-expression in liver of Lepr(-/-) mice, metabolic phenotyping Nature medicine High 17268472
2008 Hepatic AdipoR2 signaling promotes PPAR-α activity and catalase expression; knockdown of AdipoR2 diminishes PPAR-α signaling (decreased ACO and catalase), increases lipid peroxidation and ROS accumulation, and worsens NASH pathology; overexpression reverses these effects. Adenovirus-mediated shRNA knockdown and overexpression in mice on MCD diet; primary hepatocyte culture with TGF-β; gene expression and ROS assays Hepatology (Baltimore, Md.) High 18666257
2008 AdipoR2 (along with AdipoR1) mediates adiponectin-stimulated ERK1/2 activation through a Src kinase- and Ras-dependent pathway; downregulation of the adapter protein APPL1 impairs this signaling; simultaneous knockdown of both receptors attenuates ERK1/2 activation, while overexpression of either receptor or adiponectin promotes HEK293 cell growth. RNA interference in HEK293 cells, pharmacological inhibition (PP2, Clostridium difficile toxin B), Ras activation assay, cell growth assay Biochemistry High 18842004
2010 AdipoR2 (but not AdipoR1) serves as the dominant receptor for adiponectin in suppression of scavenger receptor A type 1 (SR-AI) and upregulation of IL-1Ra in macrophage foam cells; the adapter protein APPL1 mediates adiponectin-induced inhibition of lipid accumulation and NF-κB, and Akt phosphorylation through both receptors. Lentiviral-shRNA knockdown of AdipoR1, AdipoR2, and APPL1 in THP-1 monocytes; foam cell transformation with oxLDL; gene expression and protein analysis Atherosclerosis High 22227293
2010 ERp46 interacts specifically with AdipoR1 (not AdipoR2), mediated by the cytoplasmic N-terminal residues (1–70) of AdipoR1; ERp46 knockdown increases surface levels of both AdipoR1 and AdipoR2 and enhances adiponectin-stimulated AMPK phosphorylation, while reducing p38MAPK phosphorylation. Co-immunoprecipitation followed by mass spectrometry, GST-fusion protein pulldown with truncated constructs, indirect immunofluorescence, subcellular fractionation, siRNA knockdown, phosphorylation assays Biochemical and biophysical research communications High 20074551
2010 AdipoR2 expression in the anterior cingulate cortex is regulated by alcohol in a K-ras-dependent manner; AdipoR2 null mice show attenuated withdrawal-associated increased drinking; adiponectin increases excitability of ACC neurons through AdipoR2, an effect enhanced during alcohol withdrawal. Gene expression analysis (ACC), AdipoR2 knockout mice behavioral testing, intracellular electrophysiological recordings in brain slices Brain research Medium 20380822
2010 ATF3, induced by ER stress, transcriptionally represses AdipoR2 by binding a region between nucleotides -94 and -86 of the AdipoR2 promoter, reducing both AdipoR2 mRNA and protein in hepatocytes. Reporter gene assays with 5'-deleted AdipoR2 promoter constructs, EMSA, chromatin immunoprecipitation, siRNA/overexpression of ATF3 in HepG2 cells The FEBS journal High 20423458
2013 C. elegans PAQR-2 (AdipoR2 homolog) regulates fatty acid desaturation and phosphatidylcholine synthesis during cold adaptation to maintain membrane fluidity; genetic suppressors of paqr-2 phenotypes act through fatty acid metabolism genes and Δ9-desaturases. Suppressor screen in C. elegans, genetic epistasis analysis, fatty acid composition measurements PLoS genetics High 24068966
2013 The non-conserved N-terminal region of AdipoR2 (residues 1–81) prevents its constitutive cell-surface expression; AdipoR1 and AdipoR2 can form heterodimers, and co-expression with AdipoR1 promotes cell-surface localization of AdipoR2. Epitope-tagged receptor constructs, indirect immunofluorescence, quantitative plate-based cell-surface expression analysis, chimeric and truncated receptor constructs Biochemical and biophysical research communications High 23376713
2014 In vivo, AdipoR2 (but not AdipoR1) is required for adiponectin-dependent revascularization after hindlimb ischemia; conversely, AdipoR1 (but not AdipoR2) deficiency causes diet-induced metabolic dysfunction, revealing divergent in vivo roles of the two receptors. AdipoR1- and AdipoR2-deficient mice subjected to hindlimb ischemia surgery and diet-induced obesity models; blood flow recovery measurement; metabolic phenotyping The Journal of biological chemistry High 24742672
2015 The non-conserved N-terminal trunks of AdipoR1 and AdipoR2 define differential temporal signaling profiles: AdipoR1 peaks at 15 min and AdipoR2 at 24 h post-adiponectin stimulation; adiponectin also induces internalization of both receptors from the cell surface. Transient expression in HEK293 cells, receptor chimera analysis, temporal phosphorylation profiling of downstream effectors, cell-surface expression quantification Molecular and cellular endocrinology Medium 25892445
2015 Crystal structures of truncated human AdipoR1 (Δ88) and AdipoR2 (Δ99) were obtained at 2.8 Å and 2.4 Å resolution respectively by lipidic mesophase crystallography with anti-AdipoR1 Fv; both proteins bind lipids and show structural integrity by SPR ligand binding and thermostability assays. Protein expression in insect cells, affinity purification, lipidic mesophase crystallization, X-ray crystallography, SPR, thermostability assay, TLC of bound lipids Journal of structural and functional genomics High 25575462
2016 AdipoR2 deletion in the dentate gyrus (DG) of the hippocampus results in augmented contextual fear expression, reduced extinction, and intrinsic hyperexcitability of DG granule neurons; adiponectin and AdipoRon fail to suppress fear or neuronal excitability in AdipoR2 knockout mice, placing AdipoR2 as the necessary and sufficient receptor for these effects. DG-specific AdipoR2 knockout mice, contextual fear conditioning/extinction behavioral tests, whole-cell patch-clamp recordings in brain slices, AdipoRon pharmacology Molecular psychiatry High 27137743
2016 C. elegans PAQR-2 (AdipoR2 homolog) and its partner IGLR-2 physically interact at plasma membranes and together function as a membrane fluidity sensor; paqr-2 or iglr-2 mutants are glucose-intolerant and die in the presence of 20 mM glucose due to membrane rigidification; their function is independent of the insulin/FoxO pathway. Bimolecular fluorescence complementation (BiFC) for protein interaction, FRAP for membrane fluidity, genetic epistasis with daf-2 and daf-16, glucose intolerance assays PLoS genetics High 27082444
2017 AdipoR2 (and C. elegans PAQR-2) are essential to counter membrane rigidification caused by exogenously provided saturated fatty acids; mammalian cells with AdipoR2 knocked down by siRNA cannot prevent palmitic acid-induced membrane rigidity; this function is evolutionarily conserved. Dietary supplement experiments in C. elegans paqr-2 mutants, direct membrane fluidity measurement, siRNA KD of AdipoR2 in mammalian cells, lipidomics of phospholipid fatty acid composition PLoS genetics High 28886012
2017 AdipoR2 (but not AdipoR1) in hepatic stellate cells modulates Col1-α1, α-SMA gene expression, HSC migration, and AMPK activity in response to adiponectin, establishing AdipoR2 as the major anti-fibrotic adiponectin receptor on HSCs. AdipoR1 and AdipoR2 knockout mice in CCl4 liver fibrosis model; siRNA knockdown in primary hepatic stellate cells with adiponectin treatment; gene expression, migration assays, AMPK activity measurement Biochimica et biophysica acta. Molecular basis of disease High 29237572
2018 PAQR-2 (AdipoR2 homolog) expression in the hypodermis, gonad sheath cells, or intestine of C. elegans is sufficient to non-cell-autonomously maintain membrane fluidity throughout the organism, including in intestinal cells where PAQR-2 is not expressed; this cell-nonautonomous regulation is conserved in human HEK293 cells where AdipoR2-expressing cells normalize membrane fluidity in neighboring AdipoR2-silenced cells; Δ9 desaturases are essential effectors of this process. Mosaic analysis, tissue-specific rescue expression constructs in C. elegans, FRAP membrane fluidity assay, SCD siRNA in HEK293 cells Genetics High 29997234
2019 AdipoR1 and AdipoR2 are essential for sustaining desaturase expression and high levels of unsaturated fatty acids in membrane phospholipids of many human cell types including primary HUVECs, and for preventing membrane rigidification in cells challenged with exogenous palmitate; this function is independent of adiponectin. AdipoR1/AdipoR2 KD, FRAP, Laurdan dye generalized polarization, mass spectrometry of phospholipid fatty acid composition; experiments performed in absence of adiponectin Journal of lipid research High 30890562
2019 PAQR-2 (AdipoR2 homolog) senses temperature drop in C. elegans and promotes biosynthesis of γ-linolenic acid and arachidonic acid (ω-6 PUFAs), which initiate autophagy in the epidermis, delaying collagen decline and extending lifespan at low temperature. C. elegans genetic analysis, fatty acid profiling, autophagy assays, lifespan measurements at low temperature Nature communications High 31197136
2021 AdipoR2-deficient HEK293 cells challenged with saturated fatty acids show extensive transcriptome dysregulation similar to SREBP-deficient cells; AdipoR2 is the most important factor (among AdipoR2, SCD, FADS2, PEMT, ACSL4) for preventing membrane rigidification and excess saturation in cells challenged with exogenous SFAs; AdipoR2 deficiency impairs growth and respiration. Transcriptomics, lipidomics, growth and respiration assays, membrane property analysis in AdipoR2 KD HEK293 and HUVEC cells; comparative gene KD analysis Biochimica et biophysica acta. Molecular and cell biology of lipids High 33444759
2021 PAQR-2/IGLR-2 (AdipoR2 pathway) is the only pathway specifically essential for tolerance to dietary saturated fatty acids in a whole-organism C. elegans forward genetic screen; SFA-rich diet causes membrane rigidification in paqr-2 mutants; FRET analysis shows that the PAQR-2/IGLR-2 interaction is regulated by membrane fluidity, indicating a fluidity-sensing mechanism; the cytoplasmic N-terminal domain of PAQR-2 is dispensable for function but interaction with IGLR-2 is required. Whole-organism forward genetic screen in C. elegans, fluorescence resonance energy transfer (FRET), phospholipid fatty acid composition by mass spectrometry, FRAP membrane fluidity assay, domain deletion analysis Biochimica et biophysica acta. Molecular and cell biology of lipids High 33444761
2021 CTRP3 suppresses Th17 cell differentiation via AdipoR2 (not AdipoR1); suppression of Rorc and Stat3 expression by CTRP3 is blocked by AdipoR2 antagonist but not AdipoR1 antagonist; AdipoRon also suppresses Th17 differentiation via AdipoR2; CTRP3 deficiency enhances EAE development associated with increased Th17 population. Receptor-specific antagonists, C1qtnf3 knockout mice, Th17 differentiation assays in vitro, EAE model Frontiers in immunology Medium 34925309
2022 RNF145, an ER-resident E3 ubiquitin ligase, is a lipid-sensitive regulator that ubiquitinates and degrades AdipoR2 when membranes are enriched in unsaturated fatty acids; when membranes become saturated, RNF145 undergoes auto-ubiquitination and is degraded, stabilizing AdipoR2 whose hydrolase activity restores lipid homeostasis; this defines an autoregulatory loop controlling membrane lipid composition. Systematic proteomics of cells fed saturated vs unsaturated FAs, RNF145 and AdipoR2 interaction biochemistry, ubiquitination assays, RNF145 KO/KD, membrane fluidity and lipid composition measurements, lipotoxicity assays The EMBO journal High 35993436
2023 AdipoR2 promotes elongation of membrane-fluidizing polyunsaturated fatty acids and their incorporation into phospholipids by recruiting protein interactors; co-immunoprecipitation with MS identified HACD3 (dehydratase, third step in long-chain fatty acid elongation) and ACSL4 (activates unsaturated fatty acids for phospholipid channeling) as conserved AdipoR2/PAQR-2 interactors essential for membrane fluidity. 13C-labeled fatty acid tracing, co-immunoprecipitation of tagged AdipoR2/PAQR-2 in HEK293 cells and C. elegans followed by mass spectrometry, functional verification of interactions The Journal of biological chemistry High 37164154
2024 AdipoR2 regulates the meiosis-specific lipidome in mouse testes by promoting ELOVL2 expression (both transcriptionally and post-transcriptionally) to synthesize very-long-chain polyunsaturated fatty acids (VLC-PUFAs); AdipoR2 knockout causes depletion of VLC-PUFAs and palmitic acid accumulation, stiffening the cellular membrane, causing nuclear envelope invagination, impairing meiotic telomere distribution, and disrupting homologous synapsis, recombination, and intercellular bridge formation. AdipoR2 knockout mice, lipidomics of testes, transcriptional and protein analysis of ELOVL2, membrane fluidity assays, meiosis chromosome spread analysis, electron microscopy of nuclear envelope Nature communications High 38485951
2024 SCM-198 binds selectively to AdipoR2, with AdipoR2 R335 critical for binding/signaling and Y274 serving as a molecular switch for Ca2+ influx; SCM-198-AdipoR2 interaction causes Ca2+ influx, elevates phosphorylation of CaMKII and NOS3 in an AdipoR2-CaM-CaMKII-NOS3 complex, rapidly inducing nitric oxide production for liver protection. Molecular docking, site-directed mutagenesis (R335, Y274), co-immunoprecipitation identifying AdipoR2-CaM-CaMKII-NOS3 complex, Ca2+ influx measurement, NOS3 phosphorylation assay, ALF mouse model Nature communications High 39681560
2018 miR-449a targets AdipoR2 (confirmed by luciferase reporter assay) and suppresses its expression; loss of AdipoR2 reduces its interaction with E-cadherin in lipid rafts, promoting endothelial-to-mesenchymal transition (EndMT) and atherosclerosis in endothelial cells. Luciferase reporter assay, miR-449a mimic/inhibitor transfection, lipid raft isolation, co-immunoprecipitation of AdipoR2 and E-cadherin, ApoE KO diabetic mouse atherosclerosis model Biomedicine & pharmacotherapy Medium 30551487
2006 Adiponectin downregulates AdipoR2 expression (but not AdipoR1) in adipose tissue via a feedback loop; this was shown both in transgenic mice overexpressing adiponectin (which showed decreased AdipoR2 mRNA) and in adipocytes treated with recombinant adiponectin in vitro; conversely, AdipoR2 is upregulated in adipose tissue of adiponectin-null mice. Transgenic mice with adipose-specific adiponectin overexpression, adiponectin-null mice, 3T3-F442A adipocyte culture with recombinant adiponectin, qPCR Biochemical and biophysical research communications High 16729974
2017 Muscle-specific overexpression of AdipoR2 (but not AdipoR1) increases PPARα and its target gene acox1 in skeletal muscle, and in obese mice promotes systemic effects including decreased weight gain, reduced epididymal fat inflammation, and increased circulating adiponectin; both AdipoR1 and AdipoR2 overexpression increase AMPK, AKT, ERK phosphorylation and GLUT4 expression. In vivo electrotransfer-mediated gene overexpression in tibialis anterior muscle of lean and obese mice; phosphorylation assays; metabolic phenotyping Scientific reports Medium 28145500
2021 AdipoR2 silencing in the presence of exogenous palmitic acid causes increased dihydroceramide levels (ceramide precursor in the de novo synthesis pathway); conversely, AdipoR2 overexpression depletes dihydroceramides; the mechanism is consistent with AdipoR2 limiting intracellular palmitic acid supply to the rate-limiting serine palmitoyl transferase step. siRNA knockdown and overexpression of AdipoR2 in cultured cells, sphingolipid profiling by mass spectrometry Lipids in health and disease Medium 34839823
2023 AdipoR2 activation by ESME (emodin succinate monoethyl ester) in hepatocytes activates CaMKK2 and LKB1 to activate AMPK, reducing lipogenesis; suppression of AdipoR2 expression or AMPK activation completely eliminates the lipid-reducing effect of ESME; AdipoR2 on the cytomembrane of HepG2 cells can be labeled by fluorescent ESME-Cy5. Molecular docking, fluorescent ligand labeling, AdipoR2 siRNA KD, AMPK inhibition, in vivo hamster/mouse hepatic steatosis models Free radical biology & medicine Medium 37044149
2024 AdipoR2-knockout mouse brains are enlarged with ~12% excess saturated fatty acids (primarily palmitic acid at the expense of oleic acid) in phosphatidylcholines across cerebrum, cerebellum, and myelin sheaths; aging AdipoR2 KO mice exhibit hyperactivity and anxiety; cell density is lower in the cerebrum of KO mice. AdipoR2 KO mouse model, lipidomics at multiple ages, histology, electron microscopy, proteomics of cerebellum, behavioral tests FASEB journal Medium 38989587
2024 AdipoR2 mediates adiponectin-induced inhibition of goat luteal steroidogenesis via AMPK; siRNA knockdown of AdipoR2 (but not AdipoR1 or T-cadherin) abolishes APN-induced AMPK phosphorylation, CYP11A1 suppression, and progesterone reduction in luteal steroidogenic cells. siRNA knockdown of AdipoR1, AdipoR2, and T-cadherin in primary goat luteal steroidogenic cells; P-AMPK measurement; steroidogenic protein and progesterone assays Cells Medium 37408227
2025 Transmission electron microscopy reveals that AdipoR2 silencing combined with palmitic acid exposure causes disruption of cytoplasmic membrane ultrastructure, mitochondrial cristae damage, and nuclear envelope blebbing; these defects are partially rescued by oleic acid supplementation; ectopic localization of PINK1 and ACSL1 to ER-apposed membranes occurs specifically in palmitate-treated cells. Transmission electron microscopy of AdipoR2 siRNA-silenced human cells challenged with palmitic acid; immunofluorescence for PINK1 and ACSL1 localization Lipids in health and disease Medium 41327238

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
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 Hepatic AdipoR2 signaling plays a protective role against progression of nonalcoholic steatohepatitis in mice. Hepatology (Baltimore, Md.) 105 18666257
2008 The adiponectin receptors AdipoR1 and AdipoR2 activate ERK1/2 through a Src/Ras-dependent pathway and stimulate cell growth. Biochemistry 105 18842004
2013 PAQR-2 regulates fatty acid desaturation during cold adaptation in C. elegans. PLoS genetics 102 24068966
2016 Adiponectin regulates contextual fear extinction and intrinsic excitability of dentate gyrus granule neurons through AdipoR2 receptors. Molecular psychiatry 94 27137743
2016 Resveratrol increases AdipoR1 and AdipoR2 expression in type 2 diabetic nephropathy. Journal of translational medicine 93 27286657
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
2019 Adiponectin receptor PAQR-2 signaling senses low temperature to promote C. elegans longevity by regulating autophagy. Nature communications 72 31197136
2006 Adiponectin downregulates its own production and the expression of its AdipoR2 receptor in transgenic mice. Biochemical and biophysical research communications 71 16729974
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
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
2009 Genetic variation in the ADIPOR2 gene is associated with liver fat content and its surrogate markers in three independent cohorts. European journal of endocrinology 60 19208777
2006 Molecular cloning and tissue expression of chicken AdipoR1 and AdipoR2 complementary deoxyribonucleic acids. Domestic animal endocrinology 60 16697136
2016 Caenorhabditis elegans PAQR-2 and IGLR-2 Protect against Glucose Toxicity by Modulating Membrane Lipid Composition. PLoS genetics 59 27082444
2010 ERp46 binds to AdipoR1, but not AdipoR2, and modulates adiponectin signalling. Biochemical and biophysical research communications 56 20074551
2008 Expression of adiponectin receptors, AdipoR1 and AdipoR2, in normal colon epithelium and colon cancer tissue. Oncology reports 56 18695895
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
2018 Down-regulation of microRNA-375 regulates adipokines and inhibits inflammatory cytokines by targeting AdipoR2 in non-alcoholic fatty liver disease. Clinical and experimental pharmacology & physiology 44 29569260
2017 The adiponectin receptor AdipoR2 and its Caenorhabditis elegans homolog PAQR-2 prevent membrane rigidification by exogenous saturated fatty acids. PLoS genetics 44 28886012
2014 microRNA-423-3p promotes tumor progression via modulation of AdipoR2 in laryngeal carcinoma. International journal of clinical and experimental pathology 42 25337209
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
2017 Wogonin mitigates nonalcoholic fatty liver disease via enhancing PPARα/AdipoR2, in vivo and in vitro. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 38 28486193
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
2010 Genetic variation in the adiponectin receptor 2 (ADIPOR2) gene is associated with coronary artery disease and increased ADIPOR2 expression in peripheral monocytes. Cardiovascular diabetology 36 20178558
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
2018 Membrane Fluidity Is Regulated Cell Nonautonomously by Caenorhabditiselegans PAQR-2 and Its Mammalian Homolog AdipoR2. Genetics 35 29997234
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
2010 AdipoR2 is transcriptionally regulated by ER stress-inducible ATF3 in HepG2 human hepatocyte cells. The FEBS journal 35 20423458
2018 miR-449a induces EndMT, promotes the development of atherosclerosis by targeting the interaction between AdipoR2 and E-cadherin in Lipid Rafts. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 32 30551487
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
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
2009 Downregulation of adiponectin/AdipoR2 is associated with steatohepatitis in obese mice. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 28 19763702
2017 Decreased Adiponectin-Mediated Signaling Through the AdipoR2 Pathway Is Associated With Carotid Plaque Instability. Stroke 25 28258256
2011 Association of ADIPOR2 gene variants with cardiovascular disease and type 2 diabetes risk in individuals with impaired glucose tolerance: the Finnish Diabetes Prevention Study. Cardiovascular diabetology 24 21943112
2014 Ginsenoside Rb1 stimulates adiponectin signaling in C2C12 muscle cells through up-regulation of AdipoR1 and AdipoR2 proteins. Pharmaceutical biology 23 25311947
2022 Regulation of membrane fluidity by RNF145-triggered degradation of the lipid hydrolase ADIPOR2. The EMBO journal 22 35993436
2021 Extensive transcription mis-regulation and membrane defects in AdipoR2-deficient cells challenged with saturated fatty acids. Biochimica et biophysica acta. Molecular and cell biology of lipids 20 33444759
2021 The C. elegans PAQR-2 and IGLR-2 membrane homeostasis proteins are uniquely essential for tolerating dietary saturated fats. Biochimica et biophysica acta. Molecular and cell biology of lipids 19 33444761
2017 In silico analysis of nonsynonymous single nucleotide polymorphisms of the human adiponectin receptor 2 (ADIPOR2) gene. Computational biology and chemistry 19 28359874
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
2010 A potential role for adiponectin receptor 2 (AdipoR2) in the regulation of alcohol intake. Brain research 18 20380822
2021 AdipoRon, an Orally Active, Synthetic Agonist of AdipoR1 and AdipoR2 Receptors Has Gastroprotective Effect in Experimentally Induced Gastric Ulcers in Mice. Molecules (Basel, Switzerland) 17 34063466
2021 The CTRP3-AdipoR2 Axis Regulates the Development of Experimental Autoimmune Encephalomyelitis by Suppressing Th17 Cell Differentiation. Frontiers in immunology 17 34925309
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
2023 AdipoR2 recruits protein interactors to promote fatty acid elongation and membrane fluidity. The Journal of biological chemistry 16 37164154
2012 Pioglitazone prevents hyperglycemia induced decrease of AdipoR1 and AdipoR2 in coronary arteries and coronary VSMCs. Molecular and cellular endocrinology 16 22820128
2012 Nutritional and hormonal modulation of adiponectin and its receptors adipoR1 and adipoR2. Vitamins and hormones 16 23017712
2020 Expression and localization of adiponectin and its receptors (AdipoR1 and AdipoR2) in the hypothalamic-pituitary-ovarian axis of laying hens. Theriogenology 15 33113442
2018 Association of Native American ancestry and common variants in ACE, ADIPOR2, MTNR1B, GCK, TCF7L2 and FTO genes with glycemic traits in Colombian population. Gene 15 30063936
2017 Muscle-specific overexpression of AdipoR1 or AdipoR2 gives rise to common and discrete local effects whilst AdipoR2 promotes additional systemic effects. Scientific reports 15 28145500
2024 Regulation of meiotic telomere dynamics through membrane fluidity promoted by AdipoR2-ELOVL2. Nature communications 13 38485951
2023 A novel small molecule AdipoR2 agonist ameliorates experimental hepatic steatosis in hamsters and mice. Free radical biology & medicine 13 37044149
2015 Expression, purification, crystallization, and preliminary X-ray crystallographic studies of the human adiponectin receptors, AdipoR1 and AdipoR2. Journal of structural and functional genomics 13 25575462
2008 Polymorphisms of ADIPOR1 and ADIPOR2 are associated with phenotypes of type 2 diabetes in Koreans. Clinical endocrinology 13 18466348
2015 ADIPOQ and ADIPOR2 gene polymorphisms: association with overweight/obesity in Mexican children. Boletin medico del Hospital Infantil de Mexico 12 29421176
2020 Expression of AdipoR1 and AdipoR2 and Serum Level of Adiponectin in Gastric Cancer. Gastrointestinal tumors 11 33173773
2020 A Potential Theragnostic Regulatory Axis for Arthrofibrosis Involving Adiponectin (ADIPOQ) Receptor 1 and 2 (ADIPOR1 and ADIPOR2), TGFβ1, and Smooth Muscle α-Actin (ACTA2). Journal of clinical medicine 11 33213041
2017 Telmisartan ameliorates adipoR1 and adipoR2 expression via PPAR-γ activation in the coronary artery and VSMCs. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 11 28837879
2017 Expression of AdipoR1 and AdipoR2 Receptors as Leptin-Breast Cancer Regulation Mechanisms. Disease markers 11 29311755
2015 Characterisation of the adiponectin receptors: Differential cell-surface expression and temporal signalling profiles of AdipoR1 and AdipoR2 are regulated by the non-conserved N-terminal trunks. Molecular and cellular endocrinology 11 25892445
2020 Sex- and season-dependent differences in the expression of adiponectin and adiponectin receptors (AdipoR1 and AdipoR2) in the hypothalamic-pituitary-adrenal axis of the Eurasian beaver (Castor fiber L.). General and comparative endocrinology 10 32739435
2008 Association of ADIPOR2 with liver function tests in type 2 diabetic subjects. Obesity (Silver Spring, Md.) 10 18719649
2018 Susceptibility of multiple polymorphisms in ADIPOQ, ADIPOR1 and ADIPOR2 genes to myocardial infarction in Han Chinese. Gene 9 29524572
2013 Characterisation of the adiponectin receptors: the non-conserved N-terminal region of AdipoR2 prevents its expression at the cell-surface. Biochemical and biophysical research communications 9 23376713
2024 Uncovering the connection between obesity and thyroid cancer: the therapeutic potential of adiponectin receptor agonist in the AdipoR2-ULK axis. Cell death & disease 8 39349421
2023 Distinct roles of ADIPOR1 and ADIPOR2: A pan-cancer analysis. Frontiers in endocrinology 8 36896172
2022 Propofol postconditioning alleviates diabetic myocardial ischemia‑reperfusion injury via the miR‑200c‑3p/AdipoR2/STAT3 signaling pathway. Molecular medicine reports 8 35211763
2021 Palmitic acid causes increased dihydroceramide levels when desaturase expression is directly silenced or indirectly lowered by silencing AdipoR2. Lipids in health and disease 8 34839823
2015 in vitro Anti-Proliferative Effect of Adiponectin on Human Endometriotic Stromal Cells through AdipoR1 and AdipoR2 Gene Receptor Expression. Iranian biomedical journal 8 26459399
2023 Overexpression of salusin‑α upregulates AdipoR2 and activates the PPARα/ApoA5/SREBP‑1c pathway to inhibit lipid synthesis in HepG2 cells. International journal of molecular medicine 7 37026514
2024 Novel role of Quercetin in ameliorating metabolic syndrome via VDR mediated activation of adiponectin/AdipoR2 signaling. Biochemistry and biophysics reports 6 39006943
2023 APN Expression in Serum and Corpus Luteum: Regulation of Luteal Steroidogenesis Is Possibly Dependent on the AdipoR2/AMPK Pathway in Goats. Cells 6 37408227
2021 AdipoR2 inhibits human glioblastoma cell growth through the AMPK/mTOR pathway. European journal of medical research 6 33752745
2015 Revealing the Strong Functional Association of adipor2 and cdh13 with adipoq: A Gene Network Study. Cell biochemistry and biophysics 5 25388841
2015 Adipo-R1 and adipo-R2 expression in colorectal adenomas and carcinomas. Asian Pacific journal of cancer prevention : APJCP 5 25640382
2024 Aging AdipoR2-deficient mice are hyperactive with enlarged brains excessively rich in saturated fatty acids. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 4 38989587
2021 Crosstalk between AdipoR1/AdipoR2 and Nrf2/HO-1 signal pathways activated by β-caryophyllene suppressed the compound 48/80 induced pseudo-allergic reactions. Clinical and experimental pharmacology & physiology 4 34314522
2024 Efficacy of ADIPOR1 and ADIPOR2 peptide-agonist AdipoRon in preventing contracture in a rabbit model of arthrofibrosis. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 3 38605593
2024 Selectively targeting the AdipoR2-CaM-CaMKII-NOS3 axis by SCM-198 as a rapid-acting therapy for advanced acute liver failure. Nature communications 3 39681560
2020 Age Associated Changes in Transcription of Adiponectin, AdipoR1 and AdipoR2 Genes in Pancreas of Rats. Cell journal 3 32779434
2016 A Variant in ADIPOR2 Is Associated with Increased Free Fatty Acid Levels in Chinese Population. Metabolic syndrome and related disorders 3 27348122
2022 A small molecule screen for paqr-2 suppressors identifies Tyloxapol as a membrane fluidizer for C. elegans and mammalian cells. Biochimica et biophysica acta. Biomembranes 2 35588889
2016 [Effects of lotus leaf on inflammatory factors and liver AdipoR2 expressions in rats with NAFLD induced by high fat diet and high glucose]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 2 28925124
2024 Reduced hepatic AdipoR2 by increased glucocorticoid mediates effect of psychosocial stress to elevate serum cholesterol. Molecular and cellular endocrinology 1 38815796
2020 Modulation of adiponectin receptors AdipoR1 and AdipoR2 by phage display-derived peptides in in vitro and in vivo models. Journal of drug targeting 1 31888393
2016 [Mechanism of action of the SIRT1-FoxO1-AdipoR2 signaling pathway in alcoholic fatty liver disease]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 1 27978938
2025 Adiponectin Signaling Ameliorates Cognitive Dysfunction in Type 2 Diabetic Mice by Activating the Hippocampal AdipoR2-PPARα/CREB Pathway. Molecular neurobiology 0 41254427
2025 Placental mitochondrial respiration is inhibited in mice with trophoblast specific AdipoR2 overexpression. Free radical biology & medicine 0 41265498
2025 Serum cortisol and AdipoR2 rs12342 were involved in the correlation between stress and serum cholesterol in a gender-specific manner. Metabolic brain disease 0 41317243
2025 Electron microscopy reveals saturated fatty acid-induced membrane defects in AdipoR2-depleted cells. Lipids in health and disease 0 41327238
2023 [Cloning of adipor1 and adipor2 genes in Rana dybowskii and its expression pattern upon infection]. Sheng wu gong cheng xue bao = Chinese journal of biotechnology 0 37154335