Adiponectin receptor 1

The adiponectin receptors, AdipoR1 and AdipoR2, serve as receptors for globular and full-length adiponectin and mediate increased AMPK and PPAR-α ligand activities, as well as fatty acid oxidation and glucose uptake by adiponectin.

In 2016, the University of Tokyo announced it was launching an investigation into anonymously made claims of fabricated and falsified data on the identification of AdipoR1 and AdipoR2.

A study first showed that activation of adiponectin receptor 1 (AdipoR1) by AdipoRon could attenuate mitochondrial dysfunction after ICH. In vivo, experimental ICH model was established by autologous blood injection in mice. AdipoRon was injected intraperitoneally (50 mg/kg). Immunofluorescence staining were performed to explicit the location of AdipoR1, AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-γ coactivator-1a (PGC1α). The PI staining was used to quantify neuronal survival. The expression of AdipoR1 and its downstream signaling molecules were detected by Western blotting. In vitro, 10 μM oxyhemoglobin (OxyHb) was used to induce the neuronal injury in SH-SY5Y cells. Annexin V-FITC/PI staining was used to detect the neuronal apoptosis and necrosis. Mitochondrial membrane potential (Δψm) was measured by a JC-1 kit and mitochondrial mass was quantified by mitochondrial fluorescent probe. In vivo, PI staining showed that the administration of AdipoRon could reduce neuronal death at 72 h after ICH in mice. AdipoRon treatment enhanced ATP levels and reduced ROS levels in perihematoma tissues, and increased the protein expression of AdipoR1, P-AMPK, PGC1α, NRF1 and TFAM. In vitro, the JC-1 staining and Mito-tracker™ Green showed that AdipoRon significantly alleviated OxyHb-induced collapse of Δψm and enhanced mitochondrial mass. Moreover, flow cytometry analysis indicated that the neurons treated with AdipoRon showed low necrotic and apoptotic rate. AdipoRon alleviates mitochondrial dysfunction after intracerebral hemorrhage via the AdipoR1-AMPK-PGC1α pathway ¹⁾.

2: Zhao L, Zhang JH, Sherchan P, Krafft PR, Zhao W, Wang S, Chen S, Guo Z, Tang J. Administration of rCTRP9 Attenuates Neuronal Apoptosis Through AdipoR1/PI3K/Akt Signaling Pathway after ICH in Mice. Cell Transplant. 2019 Jan 14:963689718822809. doi: 10.1177/0963689718822809. [Epub ahead of print] PubMed PMID: 30642187.

3: Zhao L, Chen S, Sherchan P, Ding Y, Zhao W, Guo Z, Yu J, Tang J, Zhang JH. Recombinant CTRP9 administration attenuates neuroinflammation via activating adiponectin receptor 1 after intracerebral hemorrhage in mice. J Neuroinflammation. 2018 Jul 30;15(1):215. doi: 10.1186/s12974-018-1256-8. PubMed PMID: 30060752; PubMed Central PMCID: PMC6066941.

4: Li Q, Zhu Z, Wang C, Cai L, Lu J, Wang Y, Xu J, Su Z, Zheng W, Chen X. CTRP9 ameliorates cellular senescence via PGC‑1α/AMPK signaling in mesenchymal stem cells. Int J Mol Med. 2018 Aug;42(2):1054-1063. doi: 10.3892/ijmm.2018.3666. Epub 2018 May 9. PubMed PMID: 29749459.

5: Xu N, Zhang Y, Doycheva DM, Ding Y, Zhang Y, Tang J, Guo H, Zhang JH. Adiponectin attenuates neuronal apoptosis induced by hypoxia-ischemia via the activation of AdipoR1/APPL1/LKB1/AMPK pathway in neonatal rats. Neuropharmacology. 2018 May 1;133:415-428. doi: 10.1016/j.neuropharm.2018.02.024. Epub 2018 Feb 24. PubMed PMID: 29486166.

6: Wang L, Collings CK, Zhao Z, Cozzolino KA, Ma Q, Liang K, Marshall SA, Sze CC, Hashizume R, Savas JN, Shilatifard A. A cytoplasmic COMPASS is necessary for cell survival and triple-negative breast cancer pathogenesis by regulating metabolism. Genes Dev. 2017 Oct 15;31(20):2056-2066. doi: 10.1101/gad.306092.117. Epub 2017 Nov 14. PubMed PMID: 29138278; PubMed Central PMCID: PMC5733497.

7: Liu X, Chen J, Zhang J. AdipoR1-mediated miR-3908 inhibits glioblastoma tumorigenicity through downregulation of STAT2 associated with the AMPK/SIRT1 pathway. Oncol Rep. 2017 Jun;37(6):3387-3396. doi: 10.3892/or.2017.5589. Epub 2017 Apr 20. PubMed PMID: 28440504.

8: Yue L, Zhao L, Liu H, Li X, Wang B, Guo H, Gao L, Feng D, Qu Y. Adiponectin Protects against Glutamate-Induced Excitotoxicity via Activating SIRT1-Dependent PGC-1α Expression in HT22 Hippocampal Neurons. Oxid Med Cell Longev. 2016;2016:2957354. doi: 10.1155/2016/2957354. Epub 2016 Nov 30. PubMed PMID: 28042384; PubMed Central PMCID: PMC5155107.

9: Han Q, Shu Z, Liang X, Mi R, Yang L, Li P. Relationship between adiponectin receptor 1 gene polymorphisms and ischemic stroke. Int J Clin Exp Med. 2015 Sep 15;8(9):16719-23. eCollection 2015. PubMed PMID: 26629210; PubMed Central PMCID: PMC4659098.

10: Yang Y, Hu W, Jiang S, Wang B, Li Y, Fan C, Di S, Ma Z, Lau WB, Qu Y. The emerging role of adiponectin in cerebrovascular and neurodegenerative diseases. Biochim Biophys Acta. 2015 Sep;1852(9):1887-94. doi: 10.1016/j.bbadis.2015.06.019. Epub 2015 Jun 26. Review. PubMed PMID: 26118345.

11: Tada Y, Yagi K, Uno M, Matsushita N, Kanematsu Y, Kuwayama K, Shimada K, Nishi K, Hirasawa M, Satomi J, Kitazato KT, Kageji T, Matsuura E, Nagahiro S. Improvement of Plasma Biomarkers after Switching Stroke Patients from Other Angiotensin II Type I Receptor Blockers to Olmesartan. J Stroke Cerebrovasc Dis. 2015 Jul;24(7):1487-92. doi: 10.1016/j.jstrokecerebrovasdis.2015.03.015. Epub 2015 Apr 16. PubMed PMID: 25891757.

12: Lee YH, Petkova AP, Konkar AA, Granneman JG. Cellular origins of cold-induced brown adipocytes in adult mice. FASEB J. 2015 Jan;29(1):286-99. doi: 10.1096/fj.14-263038. Epub 2014 Nov 12. PubMed PMID: 25392270; PubMed Central PMCID: PMC4285542.

13: Contreras GA, Lee YH, Mottillo EP, Granneman JG. Inducible brown adipocytes in subcutaneous inguinal white fat: the role of continuous sympathetic stimulation. Am J Physiol Endocrinol Metab. 2014 Nov 1;307(9):E793-9. doi: 10.1152/ajpendo.00033.2014. Epub 2014 Sep 2. PubMed PMID: 25184993; PubMed Central PMCID: PMC4216946.

14: Yan W, Zhang F, Zhang R, Zhang X, Wang Y, Zhou F, Xia Y, Liu P, Gao C, Wang H, Zhang L, Zhou J, Gao F, Gao E, Koch WJ, Wang H, Cheng H, Qu Y, Tao L. Adiponectin regulates SR Ca(2+) cycling following ischemia/reperfusion via sphingosine 1-phosphate-CaMKII signaling in mice. J Mol Cell Cardiol. 2014 Sep;74:183-92. doi: 10.1016/j.yjmcc.2014.05.010. Epub 2014 May 20. PubMed PMID: 24852843.

15: Takeuchi S, Wada K, Uozumi Y, Otani N, Osada H, Nagatani K, Mori K. Adiponectin receptor 1 expression is associated with carotid plaque stability. Neurol India. 2013 May-Jun;61(3):249-53. doi: 10.4103/0028-3886.115063. PubMed PMID: 23860143.

16: Libè R, Morpurgo PS, Cappiello V, Maffini A, Bondioni S, Locatelli M, Zavanone M, Beck-Peccoz P, Spada A. Ghrelin and adiponectin in patients with Cushing's disease before and after successful transsphenoidal surgery. Clin Endocrinol (Oxf). 2005 Jan;62(1):30-6. PubMed PMID: 15638867.