Research progress on the roles and mechanisms of adiponectin and its receptors in cerebral ischemia-reperfusion injury_West China Medical Journal

Authors：

NIU Qingsheng ¹ , SU Shitong ² , HE Yarong ¹ , LIANG Lianjing ¹ ,  YAO Peng ¹

1. Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital / West China School of Medicine, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Department of Pathology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding?author：

YAO Peng, Email: yaopeng2022@wchscu.cn

Keywords：

Adiponectin; adiponectin receptors; cerebral ischemia-reperfusion injury; neuroprotection

DOI：

10.7507/1002-0179.202510007

Video：

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Abstract Full text Figures/Tables Video References Cited by

Effective neuroprotective strategies are still lacking for cerebral ischemia-reperfusion injury secondary to ischemic stroke and cardiac arrest-cardiopulmonary resuscitation. Growing evidence suggests that adiponectin (APN) and its receptors exert pivotal protective effects in these pathological processes. This article summarizes the underlying mechanisms and translational potential of the APN signaling pathway. Exogenous interventions, including recombinant APN, APN peptides, and gene transfection, exert neuroprotective effects through multiple mechanisms such as anti-inflammatory and antioxidant actions, attenuation of excitotoxicity, and inhibition of apoptosis. Endogenous regulatory strategies, such as exercise preconditioning and pharmacological interventions, can upregulate APN and its receptor expression to mitigate injury. In addition, members of the APN homologous CTRP family exhibit synergistic neuroprotective potential. Integrating evidence from basic and clinical studies, targeting the APN pathway provides a promising therapeutic strategy for cerebral ischemia–reperfusion injury.

Citation： NIU Qingsheng, SU Shitong, HE Yarong, LIANG Lianjing, YAO Peng. Research progress on the roles and mechanisms of adiponectin and its receptors in cerebral ischemia-reperfusion injury. West China Medical Journal, 2025, 40(11): 1859-1864. doi: 10.7507/1002-0179.202510007 Copy

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2.	Sekhon MS, Taccone FS, Skrifvars MB, et al. Clinical heterogeneity and phenotyping of post cardiac arrest brain injury: one size may not fit all. Intensive Care Med, 2025, 51(7): 1240-1255.
3.	Sandroni C, Cronberg T, Sekhon M. Brain injury after cardiac arrest: pathophysiology, treatment, and prognosis. Intens Care Med, 2021, 47(12): 1393-1414.
4.	Fisher M, Savitz SI. Pharmacological brain cytoprotection in acute ischaemic stroke - renewed hope in the reperfusion era. Nat Rev Neurol, 2022, 18(4): 193-202.
5.	Lei X, Qiu S, Yang G, et al. Adiponectin and metabolic cardiovascular diseases: therapeutic opportunities and challenges. Genes Dis, 2023, 10(4): 1525-1536.
6.	Zaharia AL, Oprea VD, Coad? CA, et al. Serum adiponectin levels increase in acute ischemic stroke and correlate with patients’ outcomes: a pilot study. Biomedicines, 2024, 12(8): 1828.
7.	Tu WJ, Qiu HC, Liu YK, et al. Elevated levels of adiponectin associated with major adverse cardiovascular and cerebrovascular events and mortality risk in ischemic stroke. Cardiovasc Diabetol, 2020, 19(1): 125.
8.	Khoramipour K, Chamari K, Hekmatikar AA, et al. Adiponectin: structure, physiological functions, role in diseases, and effects of nutrition. Nutrients, 2021, 13(4): 1180.
9.	Sowka A, Dobrzyn P. Role of perivascular adipose tissue-derived adiponectin in vascular homeostasis. Cells, 2021, 10(6): 1485.
10.	Ramakrishnan N, Auger K, Rahimi N, et al. Biochemistry, adiponectin//StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2025.
11.	Zhao SG, Kusminski CM, Scherer PE. Adiponectin, leptin and cardiovascular disorders. Circ Res, 2021, 128(1): 136-149.
12.	Han Y, Sun Q, Chen W, et al. New advances of adiponectin in regulating obesity and related metabolic syndromes. J Pharm Anal, 2024, 14(5): 100913.
13.	Ruiz M, Devkota R, Kaper D, et al. AdipoR2 recruits protein interactors to promote fatty acid elongation and membrane fluidity. J Biol Chem, 2023, 299(6): 104799.
14.	Vasiliauskaité-Brooks I, Sounier R, Rochaix P, et al. Structural insights into adiponectin receptors suggest ceramidase activity. Nature, 2017, 544(7648): 120-123.
15.	Roy B, Palaniyandi SS. Tissue-specific role and associated downstream signaling pathways of adiponectin. Cell Biosci, 2021, 11(1): 77.
16.	Rubina KA, Semina E, Kalinina NI, et al. Revisiting the multiple roles of T-cadherin in health and disease. Eur J Cell Biol, 2021, 100(7/8): 151183.
17.	Nishimura M, Izumiya Y, Higuchi A, et al. Adiponectin prevents cerebral ischemic injury through endothelial nitric oxide synthase-dependent mechanisms. Circulation, 2008, 117(2): 216-223.
18.	Agbaedeng TA, Iroga PE, Rathnasekara VM, et al. Adipokines and stroke: a systematic review and meta-analysis of disease risk and patient outcomes. Obes Rev, 2024, 25(4): e13684.
19.	Yu L, Wang J, Xia Y, et al. Adiponectin promotes neurogenesis after transient cerebral ischemia through STAT3 mediated BDNF upregulation in astrocytes. Neurochem Res, 2023, 48(2): 641-657.
20.	Eskut N, Cetiner M, Akdag G, et al. Effect of adiponectin on acute experimental cerebral ischemia/reperfusion injury. Turk Neurosurg, 2023, 33(2): 296-301.
21.	Zhang C, Zhen L, Fang Z, et al. Adiponectin treatment attenuates cerebral ischemia-reperfusion injury through HIF-1α-mediated antioxidation in mice. Oxid Med Cell Longev, 2021, 2021: 5531048.
22.	Liu B, Liu J, Wang J, et al. Adiponectin protects against cerebral ischemic injury through adipoR1/AMPK pathways. Front Pharmacol, 2019, 10: 597.
23.	Bai H, Zhao L, Liu H, et al: Adiponectin confers neuroprotection against cerebral ischemia-reperfusion injury through activating the cAMP/PKA-CREB-BDNF signaling. Brain Res Bull, 2018, 143: 145-154.
24.	Wang BD, Guo H, Li X, et al. Adiponectin attenuates oxygen-glucose deprivation-induced mitochondrial oxidative injury and apoptosis in hippocampal HT22 cells via the JAK2/STAT3 pathway. Cell Transplant, 2018, 27(12): 1731-1743.
25.	Xu N, Zhang Y, Doycheva D, et al. Adiponectin attenuates neuronal apoptosis induced by hypoxia-ischemia via the activation of AdipoR1/APPL1/LKB1/AMPK pathway in neonatal rats. Neuropharmacology, 2018, 133: 415-428.
26.	He Y, Liu B, Yao P, et al. Adiponectin inhibits cardiac arrest/cardiopulmonary resuscitation-induced apoptosis in brain by increasing autophagy involved in AdipoR1-AMPK signaling. Mol Med Rep, 2020, 22(2): 870-878.
27.	Lei Y, Sung HK, Burger D, et al. The therapeutic potential of adiponectin and extracellular vesicles for promoting improved healthspan. Ageing Res Rev, 2025, 111: 102823.
28.	Liu H, Wu X, Luo J, et al. Adiponectin peptide alleviates oxidative stress and NLRP3 inflammasome activation after cerebral ischemia-reperfusion injury by regulating AMPK/GSK-3β. Exp Neurol, 2020, 329: 113302.
29.	Li X, Guo H, Zhao L, et al. Adiponectin attenuates NADPH oxidase-mediated oxidative stress and neuronal damage induced by cerebral ischemia-reperfusion injury. Biochim Biophys Acta Mol Basis Dis, 2017, 1863(12): 3265-3276.
30.	Rizzo MR, Fasano R, Paolisso G. Adiponectin and cognitive decline. Int J Mol Sci, 2020, 21(6): 2010.
31.	Hong Y, Yu Q, Kong ZH, et al. Exogenous endothelial progenitor cells reached the deficient region of acute cerebral ischemia rats to improve functional recovery via Bcl-2. Cardiovasc Diagn The, 2020, 10(4): 695-704.
32.	Zhang R, Xie X, Yu Q, et al. Constitutive expression of adiponectin in endothelial progenitor cells protects a rat model of cerebral ischemia. Neural Plast, 2017, 2017: 6809745.
33.	Wang M, Li Y, Zhang R, et al. Adiponectin-transfected endothelial progenitor cells have protective effects after 2-hour middle-cerebral artery occlusion in rats with type 2 diabetes mellitus. Front Neurol, 2021, 12: 630681.
34.	Zheng M, Zhang B, Yau SSY, et al. Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin. Neural Regen Res, 2025, 20(5): 1445-1454.
35.	Hasegawa H, Yatomi K, Mitome-Mishima Y, et al. Pioglitazone prevents hemorrhagic infarction after transient focal ischemia in type 2 diabetes. Neurosci Res, 2021, 170: 314-321.
36.	Ge XL, Wang JL, Liu X, et al. Inhibition of miR-19a protects neurons against ischemic stroke through modulating glucose metabolism and neuronal apoptosis. Cell Mol Biol Lett, 2019, 24: 37.
37.	Duan J, Yin Y, Cui J, et al. Chikusetsu saponin Ⅳa ameliorates cerebral ischemia reperfusion injury in diabetic mice via adiponectin-mediated AMPK/GSK-3β pathway in vivo and in vitro. Mol Neurobiol 2016, 53(1): 728-743.
38.	Guo F, Jiang T, Song W, et al. Electroacupuncture attenuates cerebral ischemia-reperfusion injury in diabetic mice through adiponectin receptor 1-mediated phosphorylation of GSK-3β. Mol Neurobiol, 2015, 51(2): 685-695.
39.	Wu MH, Chio CC, Tsai KJ, et al. Obesity exacerbates rat cerebral ischemic injury through enhancing ischemic adiponectin-containing neuronal apoptosis. Mol Neurobiol, 2016, 53(6): 3702-3713.
40.	Romanauska A, Stankunas E, Schuldiner M, et al. Seipin governs phosphatidic acid homeostasis at the inner nuclear membrane. Nat Commun, 2024, 15(1): 10486.
41.	Chen Y, Wei LL, Tian J, et al. Seinpin knockout exacerbates cerebral ischemia/reperfusion damage in mice. Biochem Biophys Res Commun, 2016, 474(2): 377-383.
42.	Holland WL, Scherer PE. Cell biology. Ronning after the adiponectin receptors. Sci, 2013, 342(6165): 1460-1461.
43.	Okada-Iwabu M, Yamauchi T, Iwabu M, et al. A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature, 2013, 503(7477): 493-499.
44.	Barbalho SM, Laurindo LF, Zanuso BD, et al. AdipoRon’s impact on Alzheimer’s disease-a systematic review and meta-analysis. Int J Mol Sci, 2025, 26(2): 484.
45.	Ge YF, Wang T, Hu Q, et al. Adiponectin ameliorates traumatic brain injury-induced ferroptosis through AMPK-ACC1 signaling pathway. Brain Behav Immun, 2025, 126: 160-175.
46.	Fang Q, Li J, Wang Y, et al. AdipoRon engages microglia to antinociception through the adipoR1/AMPK pathway in SNI mice. Mediators Inflamm, 2023, 2023: 7661791.
47.	Bai GY, Ling J, Lu J, et al Adiponectin receptor agonist AdipoRon alleviates memory impairment in the hippocampus of septic mice. Behav Brain Res, 2024, 472: 115174.
48.	Clain J, Couret D, Planesse C, et al. Distribution of adiponectin receptors in the brain of adult mouse: effect of a single dose of the adiponectin receptor agonist, adipoRON, on ischemic stroke. Brain Sci, 2022, 12(5): 680.
49.	Zhang H, Zhang-Sun ZY, Xue CX, et al. CTRP family in diseases associated with inflammation and metabolism: molecular mechanisms and clinical implication. Acta Pharmacol Sin, 2023, 44(4): 710-725.
50.	Guan H, Wang Y, Li X, et al. C1q/tumor necrosis factor-related protein 9: basics and therapeutic potentials. Front Physiol, 2022, 13: 816218.
51.	Wang J, Ren B, Yang Y, et al. C1q/tumor necrosis factor-related protein-9 exerts antioxidant and anti-inflammatory effects on oxygen-glucose deprivation/reoxygenation-stimulated neurons by modulating the Akt-GSK-3β-Nrf2 cascade via AdipoR1. Int Immunopharmacol, 2023: 110045.
52.	Zhao W, Kong FP, Gong X, et al. Activation of adipoR1 with rCTRP9 preserves BBB integrity through the APPL1/AMPK/Nrf2 signaling pathway in ICH mice. Oxid Med Cell Longev, 2021, 2021: 2801263.
53.	Yang C, Xin JY, Liu ZL, et al. Association between serum C1q tumor necrosis factor-related protein 9 and the clinical characteristics and prognosis of ischemic stroke. Neurol Ther, 2022, 11(1): 87-101.
54.	Zhang YQ, Zhang HF, Liu XG, et al. Predictive and prognostic values of serum C1q/tumor necrosis factor-related protein 9 for first-ever ischemic stroke. Front Neurol, 2025, 16: 1526853.
55.	Fei H, Xiang P, Luo W, et al. CTRP1 attenuates cerebral ischemia/reperfusion injury via the PERK signaling pathway. Front Cell Dev Biol, 2021, 9: 700854.
56.	Niu Q, Zhu Z, Jiang Y, et al. Association between circulating plasma CTRP3 levels and acute ischemic stroke: a systematic review and meta-analysis. Front Neurosci, 2025, 19: 1582743.
57.	Li Y, Sun J, Gu L, et al. Protective effect of CTRP6 on cerebral ischemia/reperfusion injury by attenuating inflammation, oxidative stress and apoptosis in PC12 cells. Mol Med Rep, 2020, 22(1): 344-352.

1. Sharma R, Lee K. Advances in treatments for acute ischemic stroke. BMJ, 2025, 389: e076161.
2. Sekhon MS, Taccone FS, Skrifvars MB, et al. Clinical heterogeneity and phenotyping of post cardiac arrest brain injury: one size may not fit all. Intensive Care Med, 2025, 51(7): 1240-1255.
3. Sandroni C, Cronberg T, Sekhon M. Brain injury after cardiac arrest: pathophysiology, treatment, and prognosis. Intens Care Med, 2021, 47(12): 1393-1414.
4. Fisher M, Savitz SI. Pharmacological brain cytoprotection in acute ischaemic stroke - renewed hope in the reperfusion era. Nat Rev Neurol, 2022, 18(4): 193-202.
5. Lei X, Qiu S, Yang G, et al. Adiponectin and metabolic cardiovascular diseases: therapeutic opportunities and challenges. Genes Dis, 2023, 10(4): 1525-1536.
6. Zaharia AL, Oprea VD, Coad? CA, et al. Serum adiponectin levels increase in acute ischemic stroke and correlate with patients’ outcomes: a pilot study. Biomedicines, 2024, 12(8): 1828.
7. Tu WJ, Qiu HC, Liu YK, et al. Elevated levels of adiponectin associated with major adverse cardiovascular and cerebrovascular events and mortality risk in ischemic stroke. Cardiovasc Diabetol, 2020, 19(1): 125.
8. Khoramipour K, Chamari K, Hekmatikar AA, et al. Adiponectin: structure, physiological functions, role in diseases, and effects of nutrition. Nutrients, 2021, 13(4): 1180.
9. Sowka A, Dobrzyn P. Role of perivascular adipose tissue-derived adiponectin in vascular homeostasis. Cells, 2021, 10(6): 1485.
10. Ramakrishnan N, Auger K, Rahimi N, et al. Biochemistry, adiponectin//StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2025.
11. Zhao SG, Kusminski CM, Scherer PE. Adiponectin, leptin and cardiovascular disorders. Circ Res, 2021, 128(1): 136-149.
12. Han Y, Sun Q, Chen W, et al. New advances of adiponectin in regulating obesity and related metabolic syndromes. J Pharm Anal, 2024, 14(5): 100913.
13. Ruiz M, Devkota R, Kaper D, et al. AdipoR2 recruits protein interactors to promote fatty acid elongation and membrane fluidity. J Biol Chem, 2023, 299(6): 104799.
14. Vasiliauskaité-Brooks I, Sounier R, Rochaix P, et al. Structural insights into adiponectin receptors suggest ceramidase activity. Nature, 2017, 544(7648): 120-123.
15. Roy B, Palaniyandi SS. Tissue-specific role and associated downstream signaling pathways of adiponectin. Cell Biosci, 2021, 11(1): 77.
16. Rubina KA, Semina E, Kalinina NI, et al. Revisiting the multiple roles of T-cadherin in health and disease. Eur J Cell Biol, 2021, 100(7/8): 151183.
17. Nishimura M, Izumiya Y, Higuchi A, et al. Adiponectin prevents cerebral ischemic injury through endothelial nitric oxide synthase-dependent mechanisms. Circulation, 2008, 117(2): 216-223.
18. Agbaedeng TA, Iroga PE, Rathnasekara VM, et al. Adipokines and stroke: a systematic review and meta-analysis of disease risk and patient outcomes. Obes Rev, 2024, 25(4): e13684.
19. Yu L, Wang J, Xia Y, et al. Adiponectin promotes neurogenesis after transient cerebral ischemia through STAT3 mediated BDNF upregulation in astrocytes. Neurochem Res, 2023, 48(2): 641-657.
20. Eskut N, Cetiner M, Akdag G, et al. Effect of adiponectin on acute experimental cerebral ischemia/reperfusion injury. Turk Neurosurg, 2023, 33(2): 296-301.
21. Zhang C, Zhen L, Fang Z, et al. Adiponectin treatment attenuates cerebral ischemia-reperfusion injury through HIF-1α-mediated antioxidation in mice. Oxid Med Cell Longev, 2021, 2021: 5531048.
22. Liu B, Liu J, Wang J, et al. Adiponectin protects against cerebral ischemic injury through adipoR1/AMPK pathways. Front Pharmacol, 2019, 10: 597.
23. Bai H, Zhao L, Liu H, et al: Adiponectin confers neuroprotection against cerebral ischemia-reperfusion injury through activating the cAMP/PKA-CREB-BDNF signaling. Brain Res Bull, 2018, 143: 145-154.
24. Wang BD, Guo H, Li X, et al. Adiponectin attenuates oxygen-glucose deprivation-induced mitochondrial oxidative injury and apoptosis in hippocampal HT22 cells via the JAK2/STAT3 pathway. Cell Transplant, 2018, 27(12): 1731-1743.
25. Xu N, Zhang Y, Doycheva D, et al. Adiponectin attenuates neuronal apoptosis induced by hypoxia-ischemia via the activation of AdipoR1/APPL1/LKB1/AMPK pathway in neonatal rats. Neuropharmacology, 2018, 133: 415-428.
26. He Y, Liu B, Yao P, et al. Adiponectin inhibits cardiac arrest/cardiopulmonary resuscitation-induced apoptosis in brain by increasing autophagy involved in AdipoR1-AMPK signaling. Mol Med Rep, 2020, 22(2): 870-878.
27. Lei Y, Sung HK, Burger D, et al. The therapeutic potential of adiponectin and extracellular vesicles for promoting improved healthspan. Ageing Res Rev, 2025, 111: 102823.
28. Liu H, Wu X, Luo J, et al. Adiponectin peptide alleviates oxidative stress and NLRP3 inflammasome activation after cerebral ischemia-reperfusion injury by regulating AMPK/GSK-3β. Exp Neurol, 2020, 329: 113302.
29. Li X, Guo H, Zhao L, et al. Adiponectin attenuates NADPH oxidase-mediated oxidative stress and neuronal damage induced by cerebral ischemia-reperfusion injury. Biochim Biophys Acta Mol Basis Dis, 2017, 1863(12): 3265-3276.
30. Rizzo MR, Fasano R, Paolisso G. Adiponectin and cognitive decline. Int J Mol Sci, 2020, 21(6): 2010.
31. Hong Y, Yu Q, Kong ZH, et al. Exogenous endothelial progenitor cells reached the deficient region of acute cerebral ischemia rats to improve functional recovery via Bcl-2. Cardiovasc Diagn The, 2020, 10(4): 695-704.
32. Zhang R, Xie X, Yu Q, et al. Constitutive expression of adiponectin in endothelial progenitor cells protects a rat model of cerebral ischemia. Neural Plast, 2017, 2017: 6809745.
33. Wang M, Li Y, Zhang R, et al. Adiponectin-transfected endothelial progenitor cells have protective effects after 2-hour middle-cerebral artery occlusion in rats with type 2 diabetes mellitus. Front Neurol, 2021, 12: 630681.
34. Zheng M, Zhang B, Yau SSY, et al. Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin. Neural Regen Res, 2025, 20(5): 1445-1454.
35. Hasegawa H, Yatomi K, Mitome-Mishima Y, et al. Pioglitazone prevents hemorrhagic infarction after transient focal ischemia in type 2 diabetes. Neurosci Res, 2021, 170: 314-321.
36. Ge XL, Wang JL, Liu X, et al. Inhibition of miR-19a protects neurons against ischemic stroke through modulating glucose metabolism and neuronal apoptosis. Cell Mol Biol Lett, 2019, 24: 37.
37. Duan J, Yin Y, Cui J, et al. Chikusetsu saponin Ⅳa ameliorates cerebral ischemia reperfusion injury in diabetic mice via adiponectin-mediated AMPK/GSK-3β pathway in vivo and in vitro. Mol Neurobiol 2016, 53(1): 728-743.
38. Guo F, Jiang T, Song W, et al. Electroacupuncture attenuates cerebral ischemia-reperfusion injury in diabetic mice through adiponectin receptor 1-mediated phosphorylation of GSK-3β. Mol Neurobiol, 2015, 51(2): 685-695.
39. Wu MH, Chio CC, Tsai KJ, et al. Obesity exacerbates rat cerebral ischemic injury through enhancing ischemic adiponectin-containing neuronal apoptosis. Mol Neurobiol, 2016, 53(6): 3702-3713.
40. Romanauska A, Stankunas E, Schuldiner M, et al. Seipin governs phosphatidic acid homeostasis at the inner nuclear membrane. Nat Commun, 2024, 15(1): 10486.
41. Chen Y, Wei LL, Tian J, et al. Seinpin knockout exacerbates cerebral ischemia/reperfusion damage in mice. Biochem Biophys Res Commun, 2016, 474(2): 377-383.
42. Holland WL, Scherer PE. Cell biology. Ronning after the adiponectin receptors. Sci, 2013, 342(6165): 1460-1461.
43. Okada-Iwabu M, Yamauchi T, Iwabu M, et al. A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature, 2013, 503(7477): 493-499.
44. Barbalho SM, Laurindo LF, Zanuso BD, et al. AdipoRon’s impact on Alzheimer’s disease-a systematic review and meta-analysis. Int J Mol Sci, 2025, 26(2): 484.
45. Ge YF, Wang T, Hu Q, et al. Adiponectin ameliorates traumatic brain injury-induced ferroptosis through AMPK-ACC1 signaling pathway. Brain Behav Immun, 2025, 126: 160-175.
46. Fang Q, Li J, Wang Y, et al. AdipoRon engages microglia to antinociception through the adipoR1/AMPK pathway in SNI mice. Mediators Inflamm, 2023, 2023: 7661791.
47. Bai GY, Ling J, Lu J, et al Adiponectin receptor agonist AdipoRon alleviates memory impairment in the hippocampus of septic mice. Behav Brain Res, 2024, 472: 115174.
48. Clain J, Couret D, Planesse C, et al. Distribution of adiponectin receptors in the brain of adult mouse: effect of a single dose of the adiponectin receptor agonist, adipoRON, on ischemic stroke. Brain Sci, 2022, 12(5): 680.
49. Zhang H, Zhang-Sun ZY, Xue CX, et al. CTRP family in diseases associated with inflammation and metabolism: molecular mechanisms and clinical implication. Acta Pharmacol Sin, 2023, 44(4): 710-725.
50. Guan H, Wang Y, Li X, et al. C1q/tumor necrosis factor-related protein 9: basics and therapeutic potentials. Front Physiol, 2022, 13: 816218.
51. Wang J, Ren B, Yang Y, et al. C1q/tumor necrosis factor-related protein-9 exerts antioxidant and anti-inflammatory effects on oxygen-glucose deprivation/reoxygenation-stimulated neurons by modulating the Akt-GSK-3β-Nrf2 cascade via AdipoR1. Int Immunopharmacol, 2023: 110045.
52. Zhao W, Kong FP, Gong X, et al. Activation of adipoR1 with rCTRP9 preserves BBB integrity through the APPL1/AMPK/Nrf2 signaling pathway in ICH mice. Oxid Med Cell Longev, 2021, 2021: 2801263.
53. Yang C, Xin JY, Liu ZL, et al. Association between serum C1q tumor necrosis factor-related protein 9 and the clinical characteristics and prognosis of ischemic stroke. Neurol Ther, 2022, 11(1): 87-101.
54. Zhang YQ, Zhang HF, Liu XG, et al. Predictive and prognostic values of serum C1q/tumor necrosis factor-related protein 9 for first-ever ischemic stroke. Front Neurol, 2025, 16: 1526853.
55. Fei H, Xiang P, Luo W, et al. CTRP1 attenuates cerebral ischemia/reperfusion injury via the PERK signaling pathway. Front Cell Dev Biol, 2021, 9: 700854.
56. Niu Q, Zhu Z, Jiang Y, et al. Association between circulating plasma CTRP3 levels and acute ischemic stroke: a systematic review and meta-analysis. Front Neurosci, 2025, 19: 1582743.
57. Li Y, Sun J, Gu L, et al. Protective effect of CTRP6 on cerebral ischemia/reperfusion injury by attenuating inflammation, oxidative stress and apoptosis in PC12 cells. Mol Med Rep, 2020, 22(1): 344-352.

West China Medical Journal

Research progress on the roles and mechanisms of adiponectin and its receptors in cerebral ischemia-reperfusion injury

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