Skip to main content

Advertisement

SpringerLink
Log in

Adiponectin: Protection of the endothelium

  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Low levels of adiponectin, a fat-derived hormone, are found in coronary heart disease, type 2 diabetes, obesity, and other insulin-resistant states. Conversely, high adiponectin levels are predictive of reduced coronary risk in long-term epidemiologic studies. A close association between hypoadiponectinemia and endothelial dysfunction has also been demonstrated. The various mechanisms through which adiponectin may protect the endothelium, via its insulin-sensitizing, antiatherogenic, anti-inflammatory, and antioxidant properties, are reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Rimm EB, Stampfer MJ, Giovannucci E, et al.: Body size and fat distribution as predictors of coronary heart disease among middle-aged and older US men. Am J Epidmiol 1995, 141:1171–1127.

    Google Scholar 

  2. Rexrode KM, Carey VJ, Hennekens CH, et al.: Abdominal adiposity and coronary heart disease in women. JAMA 1998, 280:2284–2285.

    Article  Google Scholar 

  3. Thomas GN, Ho SY, Lam KSL, et al.: Impact of obesity and body fat distribution on cardiovascular risk factors in Hong Kong Chinese. Obes Res 2004, 12:1805–1813.

    Article  PubMed  Google Scholar 

  4. Furukawa S, Fujita T, Shimabukuro M, et al.: Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004, 14:1752–1761.

    Article  CAS  Google Scholar 

  5. Kubota N, Terauchi Y, Yamauchi T, et al.: Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem 2002, 277:25863–25866.

    Article  PubMed  CAS  Google Scholar 

  6. Matsuda M, Shimomura I, Sata M, et al.: Role of adiponectin in preventing vascular stenosis: the missing link of adipovascular axis. J Biol Chem 2002, 277:37487–37491.

    Article  PubMed  CAS  Google Scholar 

  7. Yamauchi T, Kamon J, Waki H, et al.: Globular adiponectin protected ob/ob mice from diabetes and apoE-deficient mice from atherosclerosis. J Biol Chem 2003, 278:2461–2468.

    Article  PubMed  CAS  Google Scholar 

  8. Kumada M, Kihar S, Sumitsuji S, et al.: Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol 2003, 23:85–89.

    Article  PubMed  CAS  Google Scholar 

  9. Pischon T, Girman CJ, Hotamisligil GS, et al.: Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 2004, 291:1730–1737.

    Article  PubMed  CAS  Google Scholar 

  10. Costacou T, Zgibor JC, Evans RW, et al.: The prospective association between adiponectin and coronary artery disease among individuals with type 1 diabetes. The Pittsburgh Epidemiology of Diabetes Complications Study. Diabetologia 2005, 48:41–48.

    Article  PubMed  CAS  Google Scholar 

  11. Schulze MB, Shai EB, Rimm EB, et al.: Adiponectin and future coronary heart disease events among men and type 2 diabetes. Diabetes 2005, 54:534–539.

    Article  PubMed  CAS  Google Scholar 

  12. Shimabukuro M, Higa N, Asahi T, et al.: Hypoadiponectinemia is closely linked to endothelial dysfunction in man. J Clin Endocrinol Metab 2003, 88:3236–3240.

    Article  PubMed  CAS  Google Scholar 

  13. Ouchi N, Ohishi M, Kihara S, et al.: Association of hypoadiponectinemia with impaired vasoreactivity. Hypertension 2003, 42:231–239. A very good summary of the metabolic and vascular actions of adiponectin.

    Article  PubMed  CAS  Google Scholar 

  14. Tan KCB, Xu A, Chow WS, et al.: Hypoadiponectinemia is associated with impaired endothelium-dependent vasodilation. J Clin Endocrinol Metab 2004, 89:765–769.

    Article  PubMed  CAS  Google Scholar 

  15. Wang Y, Lu G, Wong WPS, et al.: Proteomic and functional characterization of endogenous adiponectin purified from fetal bovine serum. Proteomics 2004, 4:3933–3944. A good source of information on the structure-function relationship of adiponectin.

    Article  PubMed  CAS  Google Scholar 

  16. Hotta K, Funahashi T, Arita Y, et al.: Plasma concentrations of a novel, adipose-specific, protein adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000, 20:1595–1599.

    PubMed  CAS  Google Scholar 

  17. Pajvani UB, Hawkins M, Coombs TP, et al.: Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement of insulin sensitivity. J Biol Chem 2004, 279:12152–12162.

    Article  PubMed  CAS  Google Scholar 

  18. Kobayashi H, Ouchi N, Kihara S, et al.: Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin. Circ Res 2004, 94:e27-e31.

    Article  PubMed  CAS  Google Scholar 

  19. Xu A, Chan KW, Hoo RLC, et al.: Testosterone selectively reduces the high molecular weight form of adiponectin by inhibiting its secretion from adipocytes. J Biol Chem 2005, 280:18073–18080.

    Article  PubMed  CAS  Google Scholar 

  20. Wang Y, Lam KSL, Xu JY, et al.: Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization dependent manner. J Biol Chem 2005, 208:18341–18347.

    Google Scholar 

  21. Feener EP, Dzau VJ: Pathogenesis of cardiovascular diseases indiabetes. In Joslin’s Diabetes Mellitus. Edited by Kahn CR, et al. Philadelphia: Lippincott Williams & Wilkins; 2005:867–884.

    Google Scholar 

  22. Chakravarthy U, Hayes RG, Stitt AW, et al.: Constitutive nitric oxide synthase expression in retinal vascular endothelial cells is suppressed by high glucose and advanced glycation end products. Diabetes 1998, 47:945–952.

    Article  PubMed  CAS  Google Scholar 

  23. Wilson SH, Celermajer DS: Nitric oxide, cytokines and freeradicals in diabetic vascular disease. In Diabetes in the NewMillenium. Edited by Turtle J, et al. Sydney, Australia: PowerPublications; 1999:423–432.

    Google Scholar 

  24. Park JY, Takahara N, Gabriele A, et al.: Induction of endothelin-1 expression by glucose: an effect of protein kinase C activation. Diabetes 2000, 49:1239–1248.

    Article  PubMed  CAS  Google Scholar 

  25. Quehenberger P, Bierhaus A, Fasching P, et al.: Endothelin 1 transcription is controlled by nuclear factor-kappaB in AGE-stimulated cultured endothelial cells. Diabetes 2000, 49:1561–1570.

    Article  PubMed  CAS  Google Scholar 

  26. Chen H, Montagnani M, Funahashi T, et al.: Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem 2003, 278:45021–45026. Provides clear information on adiponectin and insulin signaling pathways.

    Article  PubMed  CAS  Google Scholar 

  27. Lam KSL: Dyslipidaemia and prothrombotic tendency in type 2 diabetes. In Diabetes in the New Millenium. Edited by Turtle J, et al. Sydney, Australia: Power Publications; 1999:327–335.

    Google Scholar 

  28. Tan KCB, Ai VHG, Chow WS, et al.: Influence of low density lipoprotein (LDL) subfraction profile and LDL oxidation on endothelium-dependent and independent vasodilation in patients with type 2 diabetes. J Clin Endocrinol Metab 1999, 84:3212–3215.

    Article  PubMed  CAS  Google Scholar 

  29. Libby P, Ridhar PM, Maseri A: Inflammation and atherosclerosis. Circulation 2002, 105:1135–1143.

    Article  PubMed  CAS  Google Scholar 

  30. Matsuzawa Y, Funahashi T, Kihra S, Shimomura I: Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol 2004, 24:29–33. A key reference on the role of adiponectin in the metabolic syndromeand cardiovascular diseases.

    Article  PubMed  CAS  Google Scholar 

  31. Lam KSL, Xu A, Tan KCB, et al.: Serum adiponectin is reduced in acromegaly and normalized after correction of growth hormone excess. J Clin Endocrinol Metab 2004, 89:5448–5453.

    Article  PubMed  CAS  Google Scholar 

  32. Yamauchi T, Lamon J, Minokoshi Y, et al.: Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 2001, 8:1288–1295.

    Article  CAS  Google Scholar 

  33. Maeda N, Shimomura I, Kishida K, et al.: Diet induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 2002, 8:731–737.

    Article  PubMed  CAS  Google Scholar 

  34. Xu A, Wang Y, Keshaw H, et al.: The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver disease in mice. J Clin Invest 2003, 112:91–100.

    Article  PubMed  CAS  Google Scholar 

  35. XuA, Yin S, Wong LC, et al.: Adiponectin ameliorates dyslipidemia induced by the human immunodeficiency virus protease inhibitor ritonavir in mice. Endocrinology 2004, 145:487–494. A good reference on the effects of adiponectin on lipid metabolism.

    Article  PubMed  CAS  Google Scholar 

  36. Hattori Y, Suzuki M, Hattori S, Kasai K: Globular adiponectin upregulates nitric oxide production in vascular endothelial cells. Diabetologia 2003, 46:1543–1549.

    Article  PubMed  CAS  Google Scholar 

  37. MotoshimaH, Wu XD, Mahadev K, Goldstein BJ: Adiponectin suppresses proliferation and superoxide generation and enhances eNOS activity in endothelial cells treated with oxidized LDL. Biochem Biophys Res Commun 2004, 315:264–271. The first report on the antioxidant property of adiponectin.

    Article  PubMed  CAS  Google Scholar 

  38. Xu A, Hoo RCL, Lam MCW, et al.: Adenovirus-mediatedexpression of adiponectin alleviates endothelial dysfunctionand oxidative stress associated with db/db diabetic mice. Paper presented at the 87th Annual Meeting of the EndocrineSociety. San Diego, CA; June 4–7, 2005.

  39. Danesh J, Whincup P, Walker M, et al.: Low grade inflammation and coronary heart disease: prospective study and updated meta-analysis. BMJ 2000, 321:1999–1204.

    Google Scholar 

  40. Tan KCB, Chow WS, Tam SCF, et al.: Atorvastatin lowers C-reactive protein and improves endothelium-dependent vasodilation in type 2 diabetes mellitus. J Clin Endocrinol Metab 2002, 87:563–568.

    Article  PubMed  CAS  Google Scholar 

  41. Cacicedo JM, Yagihashi N, Keaney JF Jr, et al.: AMPK inhibits fatty acid-induced increases in NF-kappaB transactivation in cultured human umbilical vein endothelial cells. Biochem Biophys Res Commun 2004, 324:1204–1209.

    Article  PubMed  CAS  Google Scholar 

  42. Xu H, Barnes GT, Yan Q, et al.: Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003, 112:1821–1830.

    Article  PubMed  CAS  Google Scholar 

  43. Okamoto Y, Kihara S, Ouchi N, et al.: Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation 2002, 106:2767–2770.

    Article  PubMed  CAS  Google Scholar 

  44. Ouchi N, Kihara S, Arita Y, et al.: Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 1999, 100:2473–2476.

    PubMed  CAS  Google Scholar 

  45. OuchiN, Kihara S, Arita Y, et al.: Adiponectin, an adipocytederived plasma protein, inhibits endothelial NFkappaB signaling through a cAMP-dependent pathway. Circulation 2000, 102:1296–1301. A key study on the anti-inflammatory action of adiponectin.

    PubMed  CAS  Google Scholar 

  46. Fasshauer M, Kralisch S, Klier M, et al.: Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Commun 2003, 301:1045–1050.

    Article  PubMed  CAS  Google Scholar 

  47. Kawanami D, Maemura K, Takeda N, et al.: Direct reciprocal effects of resistin and adiponectin on vascular endothelial cells: a new insight into adipocytokine-endothelial cell interaction. Biochem Biophys Res Commun 2004, 314:415–419.

    Article  PubMed  CAS  Google Scholar 

  48. Dandona P, Aljada A: Endothelial dysfunction in patients with type 2 diabetes and the effects of thiazolidinedione antidiabetic agents. J Diabetes Complications 2004, 18:91–102.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine and Research Centre of Heart, Brain, Hormone & Healthy Aging, Medical Faculty, University of Hong Kong, 21, Sassoon Road, Pokfulam, Hong Kong

    Karen S. L. Lam MD & Aimin Xu PhD

Authors
  1. Karen S. L. Lam MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aimin Xu PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lam, K.S.L., Xu, A. Adiponectin: Protection of the endothelium. Curr Diab Rep 5, 254–259 (2005). https://doi.org/10.1007/s11892-005-0019-y

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11892-005-0019-y

Keywords

Search

Navigation