Adiponectin receptor agonist AdipoRon modulates human and mouse platelet function

Xiang-hui Zhou1,2, Zhi-peng Cheng1,2, Meng Lu3, Wen-yi Lin1,2, Li-li Luo1,2, Zhang-yin Ming3,4, Yu Hu1,2,5
1 Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
2 Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan 430030, China
3 Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China
4 Tongji-Rongcheng Center for Biomedicine, Huazhong University of Science and Technology, Wuhan 430030, China
5 Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan 430022, China
Correspondence to: Yu Hu:,
DOI: 10.1038/s41401-022-00943-1
Received: 25 January 2022
Accepted: 14 June 2022
Advance online: 2 August 2022


Adiponectin, an adipokine secreted by adipocytes, has anti-atherosclerotic and antithrombotic activities. AdipoRon is synthetic small molecule adiponectin receptor agonist. In this study, we investigated the effect of AdipoRon on platelet activation and thrombus formation. Washed human platelets were prepared from the peripheral blood of healthy donors. In a series of in vitro platelet functional assays, pre-treatment with AdipoRon (10, 20, 40 μg/mL) dose-dependently inhibited the aggregation, granule secretion and spreading of washed human platelets. We showed that AdipoRon (20, 40 μg/mL) significantly inhibited AMPK, Syk, PLCγ2, PI3K, Akt, p38-MAPK and ERK1/2 signalling pathways in washed human platelets. In addition, we demonstrated that the phosphorylation of CKII at Tyr255 was an important mechanism of the integrin αIIbβ3-mediated platelet activation. Meanwhile, AdipoR1 deficiency impaired the inhibitory effect of AdipoRon on mouse platelets. In ferric chloride-induced carotid injury model, injection of AdipoRon (5 or 12.5 mg/kg, iv) significantly attenuated arterial thrombosis. In conclusion, AdipoRon attenuates platelet function via the AdipoR1/AMPK/CKII/PI3K/AKT signalling pathways, while exerting a protective effect against arterial thrombosis. This study offers new insights into the fields of cardiovascular disease and antiplatelet drug discovery.
Keywords: adiponectin; adipoRon; platelet activation; signalling pathway; thrombosis; antiplatelet drug

Article Options

Download Citation

Cited times in Scopus