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대사 및 심혈관계 질환에 대한 아디포넥틴 수용체 활성제, 아디포론의 잠재적 역할

Potential Role of Adiponectin Receptor Agonist, AdipoRon in Cardiometabolic Disease

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PURPOSE: Adiponectin has beneficial effects on metabolic and cardiovascular disease. Adiponectin receptor agonist, AdipoRon was discovered in 2013 and it may play an important role in preventing and ameliorating cardiometabolic disease. However, the physiological function and signal transduction of AdipoRon are still under way, and the potential role of AdipoRon in metabolic and cardiovascular diseases has not been clearly elucidated. The purpose of this review is to provide basic knowledge for the potential role of AdipoRon in cardiometabolic disease. METHODS: In this review, we summarized the previous studies (published between 2013 and 2019) investigating the effect of Adipo- Ron on metabolic and cardiovascular disease. RESULTS: The previous evidences have shown that AdipoRon treatment exerted its pleiotropic actions on metabolism related tissue and organs including adipose tissue, skeletal and cardiac muscles, liver, kidney, and vascular beds. Activation of adiponectin receptors may be effective for the treatment of metabolic and cardiovascular diseases due in part to activation of AMPK and PPARα signaling pathway as adiponectin does. CONCLUSIONS: In conclusion, AdipoRon can be a novel therapeutic agent for the cardiometabolic disease. However, all of previous studies were conducted using experimental animal models and it is needed to investigate the role of AdipoRon in metabolic and cardiovascular disease in human.

Abstract

PURPOSE: Adiponectin has beneficial effects on metabolic and cardiovascular disease. Adiponectin receptor agonist, AdipoRon was discovered in 2013 and it may play an important role in preventing and ameliorating cardiometabolic disease. However, the physiological function and signal transduction of AdipoRon are still under way, and the potential role of AdipoRon in metabolic and cardiovascular diseases has not been clearly elucidated. The purpose of this review is to provide basic knowledge for the potential role of AdipoRon in cardiometabolic disease. METHODS: In this review, we summarized the previous studies (published between 2013 and 2019) investigating the effect of Adipo- Ron on metabolic and cardiovascular disease. RESULTS: The previous evidences have shown that AdipoRon treatment exerted its pleiotropic actions on metabolism related tissue and organs including adipose tissue, skeletal and cardiac muscles, liver, kidney, and vascular beds. Activation of adiponectin receptors may be effective for the treatment of metabolic and cardiovascular diseases due in part to activation of AMPK and PPARα signaling pathway as adiponectin does. CONCLUSIONS: In conclusion, AdipoRon can be a novel therapeutic agent for the cardiometabolic disease. However, all of previous studies were conducted using experimental animal models and it is needed to investigate the role of AdipoRon in metabolic and cardiovascular disease in human.

참고문헌 (52)

  1. Stern JH, "Adiponectin, leptin, and fatty acids in the maintenance of metabolic homeostasis through adipose tissue crosstalk", Cell Metab, 23(5), pp.770~784 (2016)
  2. Deng Y, "Adipokines as novel biomarkers and regulators of the metabolic syndrome", Ann N Y Acad Sci, 1212, pp.E1~E19 (2010)
  3. Hotta K, "Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2diabetic patients", Arterioscler Thromb Vasc Biol, 20(6), pp.1595~1599 (2000)
  4. Fontana L, "Visceral fat adipokine secretion is associated with systemic inflammation in obese humans", Diabetes, 56(4), pp.1010~1013 (2007)
  5. Picchi A, "Tumor necrosis factor-alpha induces endothelial dysfunction in the prediabetic metabolic syndrome", Circ Res, 99(1), pp.69~77 (2006)
  6. Lee S, "Adiponectin abates diabetes-induced endothelial dysfunction by suppressing oxidative stress, adhesion molecules, and inflammation in type 2 diabetic mice", Am J Physiol Heart Circ Physiol, 303(1), pp.H106~H115 (2012)
  7. Halberg N, "Systemic fate of the adipocyte-derived factor adiponectin", Diabetes, 58(9), pp.1961~1970 (2009)
  8. Holland WL, "Cell Biology. Ronning after the adiponectin receptors", Science, 342(6165), pp.1460~1461 (2013)
  9. Okada-Iwabu M, "A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity", Nature, 503(7477), pp.493~499 (2013)
  10. Booth FW, "Role of inactivity in chronic diseases : evolutionary insight and pathophysiological mechanisms", Physiol Rev, 97(4), pp.1351~1402 (2017)
  11. Booth FW, "The erosion of physical activity in Western societies : an economic death march", Diabetologia, 58(8), pp.1730~1734 (2015)
  12. Kusminski CM, "Targeting adipose tissue in the treatment of obesity-associated diabetes", Nat Rev Drug Discov, 15(9), pp.639~660 (2016)
  13. Okamoto Y, "Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice", Circulation, 106(22), pp.2767~2770 (2002)
  14. Ouchi N, "Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocytederived macrophages", Circulation, 103(8), pp.1057~1063 (2001)
  15. Tsubakio-Yamamoto K, "Adiponectin prevents atherosclerosis by increasing cholesterol efflux from macrophages", Biochem Biophys Res Commun, 375(3), pp.390~394 (2008)
  16. Weyer C, "Hypoadiponectinemia in obesity and type 2 diabetes : close association with insulin resistance and hyperinsulinemia", J Clin Endocrinol Metab, 86(5), pp.1930~1935 (2001)
  17. Yamauchi T, "The fatderived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity", Nat Med, 7(8), pp.941~946 (2001)
  18. Berg AH, "The adipocytesecreted protein Acrp30 enhances hepatic insulin action", Nat Med, 7(8), pp.947~953 (2001)
  19. Fruebis J, "Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice", Proc Natl Acad Sci U S A, 98(4), pp.2005~2010 (2001)
  20. Choi KC, "Effect of PPAR-alpha and-gamma agonist on the expression of visfatin, adiponectin, and TNF-alpha in visceral fat of OLETF rats", Biochem Biophys Res Commun, 336(3), pp.747~753 (2005)
  21. Iwaki M, "Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors", Diabetes, 52(7), pp.1655~1663 (2003)
  22. Kubota N, "Pioglitazone ameliorates insulin resistance and diabetes by both adiponectin-dependent and-independent pathways", J Biol Chem, 281(13), pp.8748~8755 (2006)
  23. Pajvani UB, "Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity", J Biol Chem, 279(13), pp.12152~12162 (2004)
  24. 이세원, "Effects of interventions on adiponectin and adiponectin receptors", Journal of exercise rehabilitation, 10(2), pp.60~68 (2014), 한국운동재활학회[DOI]
  25. Bluher M, "Circulating adiponectin and expression of adiponectin receptors in human skeletal muscle : associations with metabolic parameters and insulin resistance and regulation by physical training", J Clin Endocrinol Metab, 91(6), pp.2310~2316 (2006)
  26. Huang H, "The effect of exercise training on adiponectin receptor expression in KKAy obese", diabetic mice, 2006, pp.189(3), 643~653
  27. Christiansen T, "Diet-induced weight loss and exercise alone and in combination enhance the expression of adiponectin receptors in adipose tissue and skeletal muscle, but only diet-induced weight loss enhanced circulating adiponectin", J Clin Endocrinol Metab, 95(2), pp.911~919 (2010)
  28. Farias JM, "Exercise training performed simultaneously to a high-fat diet reduces the degree of insulin resistance and improves adipoR1-2", APPL1 protein levels in mice, 2012, pp.11, 134~
  29. Marinho R, "Endurance exercise training increases APPL1 expression and improves insulin signaling in the hepatic tissue of diet-induced obese mice, independently of weight loss", J Cell Physiol, 227(7), pp.2917~2926 (2012)
  30. Miki Okada-Iwabu, "Perspective of Small-Molecule AdipoR Agonist for Type 2 Diabetes and Short Life in Obesity", Diabetes and Metabolism Journal, 39(5), pp.363~372 (2015), 대한당뇨병학회[DOI]
  31. Zhang BB, "AMPK : an emerging drug target for diabetes and the metabolic syndrome", Cell Metab, 9(5), pp.407~416 (2009)
  32. Zhang Y, "AdipoRon, the first orally active adiponectin receptor activator, attenuates postischemic myocardial apoptosis through both AMPK-mediated and AMPK-independent signalings", Am J Physiol Endocrinol Metab, 309(3), pp.E275~E282 (2015)
  33. Viollet B, "Targeting the AMPK pathway for the treatment of type 2 diabetes", Front Biosci(Landmark Ed), 14, pp.3380~3400 (2009)
  34. Lefebvre P, "Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis", J Clin Invest, 116(3), pp.571~580 (2006)
  35. Wang SJ, "Adiponectin receptor agonist AdipoRon suppresses adipogenesis in C3H10T1", 2 cells through the adenosine monophosphateactivated protein kinase signaling pathway, 2017, pp.16(5), 7163~7169
  36. Zhu P, "Design, synthesis chalcone derivatives as AdipoR agonist for type 2 diabetes", Chem Biol Drug Des, 92(2), pp.1525~1536 (2018)
  37. Kim Y, "The adiponectin receptor agonist AdipoRon ameliorates diabetic nephropathy in a model of type 2 diabetes", J Am Soc Nephrol, 29(4), pp.1108~1127 (2018)
  38. Choi SR, "Adiponectin receptor agonist AdipoRon decreased ceramide, and lipotoxicity, and ameliorated diabetic nephropathy", Metabolism, 85, pp.348~360 (2018)
  39. Sciarretta S, "Boosting autophagy in the diabetic heart : a translational perspective", Cardiovasc Diagn Ther, 5(5), pp.394~402 (2015)
  40. Munasinghe PE, "Type-2diabetes increases autophagy in the human heart through promotion of Beclin-1 mediated pathway", Int J Cardiol, 202, pp.13~20 (2016)
  41. Goldstein BJ, "Protective vascular and myocardial effects of adiponectin", Nat Clin Pract Cardiovasc Med, 6(1), pp.27~35 (2009)
  42. Wang Y, "Restoring diabetes-induced autophagic flux arrest in ischemic", reperfused heart by ADIPOR(adiponectin receptor)activation involves both AMPK-dependent and AMPK-independent signaling, 2017, pp.13(11), 1855~1869
  43. Wang Y, "Hepatoprotective effects of AdipoRon against d-galactosamine-induced liver injury in mice", Eur J Pharm Sci, 93, pp.123~131 (2016)
  44. Wu X, "An adiponectin receptor agonist reduces type 2 diabetic periodontitis", J Dent Res, 98, pp.313~321 (2019)
  45. Holland WL, "Inducible overexpression of adiponectin receptors highlight the roles of adiponectin-induced ceramidase signaling in lipid and glucose homeostasis", Mol Metab, 6(3), pp.267~275 (2017)
  46. Zhang N, "AdipoRon, an adiponectin receptor agonist, attenuates cardiac remodeling induced by pressure overload", J Mol Med(Berl), 96(12), pp.1345~1357 (2018)
  47. Hu X, "AdipoRon prevents l-thyroxine or isoproterenol-induced cardiac hypertrophy through regulating the AMPK-related pathway", Acta Biochim Biophys Sin (Shanghai), 51, pp.20~30 (2019)
  48. Hong K, "Adiponectin receptor agonist, AdipoRon, causes vasorelaxation predominantly via a direct smooth muscle action", Microcirculation, 23(3), pp.207~220 (2016)
  49. Fairaq A, "AdipoRon, an adiponectin receptor agonist, attenuates PDGF-induced VSMC proliferation through inhibition of mTOR signaling independent of AMPK : Implications toward suppression of neointimal hyperplasia", Pharmacol Res, 119, pp.289~302 (2017)
  50. Malih S, "Promigratory and proangiogenic effects of AdipoRon on bone marrowderived mesenchymal stem cells : an in vitro study", Biotechnol Lett, 39(1), pp.39~44 (2017)
  51. Guo R, "Adiponectin and its receptors are involved in hypertensive vascular injury", Mol Med Rep, 17(1), pp.209~215 (2018)
  52. Yamashita T, "An orally-active adiponectin receptor agonist mitigates cutaneous fibrosis, inflammation and microvascular pathology in a murine model of systemic sclerosis", Sci Rep, 8(1), pp.11843~ (2018)

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