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Pathogenesis of HAART-Associated Metabolic Syndrome

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Cardiovascular Disease in AIDS
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References

  1. Hanley AJ, Wagenknecht LE, D’Agostino RB Jr, Zinman B, Haffner SM (2003) Identification of subjects with insulin resistance and beta-cell dysfunction using alternative definitions of the metabolic syndrome. Diabetes 52:2740–2747

    PubMed  CAS  Google Scholar 

  2. Balkau B, Vernay M, Mhamdi L et al (2003) The incidence and persistence of the NCEP (National Cholesterol Education Program) metabolic syndrome. The French D.E.S.I.R. study. Diabetes Metab 29: 526–532

    PubMed  CAS  Google Scholar 

  3. Ginsberg HN (2000) Insulin resistance and cardiovascular disease. J Clin Invest 106:453–458

    Article  PubMed  CAS  Google Scholar 

  4. Leow MK, Addy CL, Mantzoros CS (2003) Clinical review 159: Human immunodeficiency virus/highly active antiretroviral therapy-associated metabolic syndrome: clinical presentation, pathophysiology, and therapeutic strategies. J Clin Endocrinol Metab 88:1961–1976

    Article  PubMed  CAS  Google Scholar 

  5. Saltiel AR, Kahn CR (2001) Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414:799–806

    Article  PubMed  CAS  Google Scholar 

  6. Randle PJ, Garland PB, Hales CN, Newsholme EA (1963) The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1:785–789

    PubMed  CAS  Google Scholar 

  7. Perseghin G, Petersen K, Shulman GI (2003) Cellular mechanism of insulin resistance: potential links with inflammation. Int J Obes Relat Metab Disord 27[Suppl 3]: S6–11

    PubMed  CAS  Google Scholar 

  8. Fasshauer M, Paschke R (2003) Regulation of adipocytokines and insulin resistance. Diabetologia 46:1594–1603

    Article  PubMed  CAS  Google Scholar 

  9. Mattison RE, Jensen M (2003) The adipocyte as an endocrine cell. Curr Opin Endocrinol Diabetes 10317–10321

    Google Scholar 

  10. Matsuzawa Y, Funahashi T, Kihara S, Shimomura I (2004) Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol 24:29–33

    PubMed  CAS  Google Scholar 

  11. Ouchi N, Kihara S, Funahashi T, Matsuzawa Y, Walsh K (2003) Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol 14:561–566

    PubMed  CAS  Google Scholar 

  12. Ruan H, Lodish HF (2003) Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha. Cytokine Growth Factor Rev 14:447–455

    Article  PubMed  CAS  Google Scholar 

  13. Lagathu C, Bastard JP, Auclair M, Maachi M, Capeau J, Caron M (2003) Chronic interleukin-6 (IL-6) treatment increased IL-6 secretion and induced insulin resistance in adipocyte: prevention by rosiglitazone. Biochem Biophys Res Commun 311:372–379

    Article  PubMed  CAS  Google Scholar 

  14. Montague CT, O’Rahilly S (2000) The perils of portliness: causes and consequences of visceral adiposity. Diabetes 49:883–888

    PubMed  CAS  Google Scholar 

  15. Lafontan M, Berlan M (2003) Do regional differences in adipocyte biology provide new pathophysiological insights? Trends Pharmacol Sci 24:276–283

    Article  PubMed  CAS  Google Scholar 

  16. Stulnig TM, Waldhausl W (2004) 11beta-Hydroxysteroid dehydrogenase type 1 in obesity and type 2 diabetes. Diabetologia 47:1–11

    Article  PubMed  CAS  Google Scholar 

  17. Lewis GF, Carpentier A, Adeli K, Giacca A (2002) Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev 23:201–229

    Article  PubMed  CAS  Google Scholar 

  18. Gan SK, Kriketos AD, Poynten AM et al (2003) Insulin action, regional fat, and myocyte lipid: altered relationships with increased adiposity. Obes Res 11:1295–1305

    Article  PubMed  CAS  Google Scholar 

  19. Schaffer JE (2003) Lipotoxicity: when tissues overeat. Curr Opin Lipidol 14:281–287

    Article  PubMed  CAS  Google Scholar 

  20. Wellen KE, Hotamisligil GS (2003) Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 112:1785–1788

    Article  PubMed  CAS  Google Scholar 

  21. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  23. Fernandez-Real JM, Ricart W (2003) Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 24:278–301

    Article  PubMed  CAS  Google Scholar 

  24. Jain RG, Furfine ES, Pedneault L, White AJ, Lenhard JM (2001) Metabolic complications associated with antiretroviral therapy. Antiviral Res 51:151–177

    Article  PubMed  CAS  Google Scholar 

  25. Perret B, Ferrand C, Bonnet E, Tercé F, Collet X (2003) Lipoprotein metabolism in HIV-positive patients. Eur J Med Res 8:[Suppl II]:6

    Google Scholar 

  26. Savès M, Raffi F, Capeau J et al (2002) Factors related to lipodystrophy and metabolic alterations in patients with human immunodeficiency virus infection receiving highly active antiretroviral therapy. Clin Infect Dis 34:1396–1405

    PubMed  Google Scholar 

  27. Purnell JQ, Zambon A, Knopp RH et al (2000) Effect of ritonavir on lipids and post-heparin lipase activities in normal subjects. AIDS 14:51–57

    Article  PubMed  CAS  Google Scholar 

  28. Van der Valk M, Kastelein JJ, Murphy RL et al (2001) Nevirapine-containing antiretroviral therapy in HIV-1 infected patients results in an anti-atherogenic lipid profile. AIDS 15:2407–2414

    PubMed  Google Scholar 

  29. Carr A, Samaras K, Thorisdottir A, Kaufmann GR, Chisholm DJ, Cooper DA (1999) Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet 353:2093–2099

    PubMed  CAS  Google Scholar 

  30. Liang JS, Distler O, Cooper DA, et al (2001) HIV protease inhibitors protect apolipoprotein B from degradation by the proteasome: a potential mechanism for protease inhibitor-induced hyperlipidemia. Nat Med 7:1327–1331

    Article  PubMed  CAS  Google Scholar 

  31. Lenhard JM, Croom DK, Weiel JE, Winegar DA (2000) HIV protease inhibitors stimulate hepatic triglyceride synthesis. Arterioscler Thromb Vasc Biol 20:2625–2629

    PubMed  CAS  Google Scholar 

  32. Riddle TM, Kuhel DG, Woollett LA, Fichtenbaum CJ, Hui DY (2001) HIV protease inhibitor induces fatty acid and sterol biosynthesis in liver and adipose tissues due to the accumulation of activated sterol regulatory element-binding proteins in the nucleus. J Biol Chem 276:37514–37519

    Article  PubMed  CAS  Google Scholar 

  33. Bonnet E, Ruidavets JB, Tuech J et al (2001) Apoprotein c-III and E-containing lipoparticles are markedly increased in HIV-infected patients treated with protease inhibitors: association with the development of lipodystrophy. J Clin Endocrinol Metab 86:296–302

    Article  PubMed  CAS  Google Scholar 

  34. Noor MA, Lo JC, Mulligan K et al (2001) Metabolic effects of indinavir in healthy HIV-seronegative men. AIDS 15:F11–18

    PubMed  CAS  Google Scholar 

  35. Noor MA, Seneviratne T, Aweeka FT et al (2002) Indinavir acutely inhibits insulin-stimulated glucose disposal in humans: a randomized, placebo-controlled study. AIDS 29:F1–8

    Google Scholar 

  36. Murata H, Hruz PW, Mueckler M (2002) Investigating the cellular targets of HIV protease inhibitors: implications for metabolic disorders and improvements in drug therapy. Curr Drug Targets Infect Disord 2:1–8

    Article  PubMed  CAS  Google Scholar 

  37. Miller J, Carr A, Emery S et al (2003) HIV lipodystrophy: prevalence, severity and correlates of risk in Australia. HIV Med 4:293–301

    Article  PubMed  CAS  Google Scholar 

  38. Mallal SA, John M, Moore CB, James IR, McKinnon EJ (2000) Contribution of nucleoside analogue reverse transcriptase inhibitors to subcutaneous fat wasting in patients with HIV infection. AIDS 14:1309–1316

    PubMed  CAS  Google Scholar 

  39. Gougeon M-L, Pénicaud L, Fromenty B, Leclercq P, Viard J-P, Capeau J (2004) Adipocytes targets and actors in the pathogenesis of HIV-associated lipodystrophy and metabolic alterations. Antivir Ther 9:161–177

    PubMed  CAS  Google Scholar 

  40. Caron M, Auclair M, Vigouroux C, Glorian M, Forest C, Capeau J (2001) The HIV protease inhibitor indinavir impairs sterol regulatory element-binding protein-1 intranuclear localization, inhibits preadipocyte differentiation, and induces insulin resistance. Diabetes 50:1378–1388

    PubMed  CAS  Google Scholar 

  41. Caron M, Auclair M, Sterlingot H, Kornprobst M, Capeau J (2003) Some HIV protease inhibitors alter lamin A/C maturation and stability, SREBP-1 nuclear localization and adipocyte differentiation. AIDS 17:2437–2444

    PubMed  CAS  Google Scholar 

  42. Krimm I, Ostlund C, Gilquin B, et al (2002) The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy. Structure (Camb) 10:811–823

    Article  PubMed  CAS  Google Scholar 

  43. Lloyd DJ, Trembath RC, Shackleton S (2002) A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies. Hum Mol Genet 11:769–777

    Article  PubMed  CAS  Google Scholar 

  44. Vigouroux C, Auclair M, Dubosclard E et al (2001) Nuclear envelope disorganization in fibroblasts from lipodystrophic patients with heterozygous R482Q/W mutations in the lamin A/C gene. J Cell Sci 114:4459–4468

    PubMed  CAS  Google Scholar 

  45. Jones SP, Janneh O, Back DJ, Pirmohamed M (2003) Altered adipocytokine gene expression in murine 3T3-F442A adipocytes treated with protease inhibitors and nucleoside reverse transcriptase inhibitors. Antivir Ther 8:L11

    Google Scholar 

  46. Lagathu C, Bastard JP, Auclair M et al (2004) HIV-1 protease inhibitors and nucleoside analogue reverse transcriptase inhibitors alter the expression and secretion of proinflammatory cytokines and adiponectin in cultured adipocytes. Antivir Ther (in press)

    Google Scholar 

  47. Caron M, Auclair M, Lagathu C et al (2004) Thymidine analogues contrary to other HIV-1 reverse transcriptase inhibitors, alter adipocyte functions in vitro. AIDS (in press)

    Google Scholar 

  48. Nolan D, Moore C, Castley A et al (2003) Tumour necrosis factor-alpha gene-238G/A promoter polymorphism associated with a more rapid onset of lipodystrophy. AIDS 17:121–123

    PubMed  Google Scholar 

  49. Bastard JP, Caron M, Vidal H et al (2002) Association between altered expression of adipogenic factor SREBP1 in lipoatrophic adipose tissue from HIV-1-infected patients and abnormal adipocyte differentiation and insulin resistance. Lancet 359:1026–1031

    Article  PubMed  CAS  Google Scholar 

  50. Domingo P, Matias-Guiu X, Pujol RM et al (1999) Subcutaneous adipocyte apoptosis in HIV-1 protease inhibitor-associated lipodystrophy. AIDS 13:2261–2267

    PubMed  CAS  Google Scholar 

  51. Lloreta J, Domingo P, Pujol RM et al (2002) Ultrastructural features of highly active antiretroviral therapy-associated partial lipodystrophy. Virchows Arch 441:599–604

    Article  PubMed  Google Scholar 

  52. Jan V, Cervera P, Maachi M et al (2004) Altered fat differentiation and adipocytokine expression are interrelated and linked to morphological changes and insulin resistance in HIV-1-infected lipodystrophic patients. Antivir Ther 9:555–564

    PubMed  CAS  Google Scholar 

  53. Sutinen J, Korsheninnikova E, Funahashi T, Matsuzawa Y, Nyman T, Yki-Jarvinen H (2003) Circulating concentration of adiponectin and its expression in subcutaneous adipose tissue in patients with highly active antiretroviral therapy-associated lipodystrophy. J Clin Endocrinol Metab 88:1907–1910

    Article  PubMed  CAS  Google Scholar 

  54. Vigouroux C, Maachi M, Nguyen TH et al (2003) Serum adipocytokines are related to lipodystrophy and metabolic disorders in HIV-infected men under antiretroviral therapy. AIDS 17:1503–1511

    Article  PubMed  CAS  Google Scholar 

  55. Martin A, Smith DE, Carr A et al (2004) Reversibility of lipoatrophy in HIV-infected patients 2 years after switching from a thymidine analogue to abacavir: the MITOX Extension Study. AIDS 18:1029–1036

    PubMed  CAS  Google Scholar 

  56. Domingo P, Matias-Guiu X, Pujol RM et al (2001) Switching to nevirapine decreases insulin levels but does not improve subcutaneous adipocyte apoptosis in patients with highly active antiretroviral therapy-associated lipodystrophy. J Infect Dis 184:1197–1201

    Article  PubMed  CAS  Google Scholar 

  57. Thomson K, McComsey, Paulsen D et al (2003) Improvements in body fat and mitochondrial DNA levels are accompanied by decreased adipose tissue cell apoptosis after replacement of stavudine therapy with either abacavir or zidovudine. 10th Conference on Retroviruses and Opportunistic Infections, Boston, 2003, p 728

    Google Scholar 

  58. Ledru E, Christeff N, Patey O, de Truchis P, Melchior JC, Gougeon ML (2000) Alteration of tumor necrosis factor-alpha T-cell homeostasis following potent antiretroviral therapy: contribution to the development of human immunodeficiency virus-associated lipodystrophy syndrome. Blood 95:3191–3198

    PubMed  CAS  Google Scholar 

  59. Rietschel P, Hadigan C, Corcoran C et al (2001) Assessment of growth hormone dynamics in human immunodeficiency virus-related lipodystrophy. J Clin Endocrinol Metab 86:504–510

    Article  PubMed  CAS  Google Scholar 

  60. Lo JC, Mulligan K, Noor MA et al (2001) The effects of recombinant human growth hormone on body composition and glucose metabolism in HIV-infected patients with fat accumulation. J Clin Endocrinol Metab 86:3480–3487

    PubMed  CAS  Google Scholar 

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Capeau, J. (2005). Pathogenesis of HAART-Associated Metabolic Syndrome. In: Barbaro, G., Boccara, F. (eds) Cardiovascular Disease in AIDS. Springer, Milano. https://doi.org/10.1007/88-470-0358-X_2

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  • DOI: https://doi.org/10.1007/88-470-0358-X_2

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