Pathogenesis of the HAART-associated metabolic syndrome

Advances in Cardiology

Volumn 40, Issue , 2003, Pages 83-96

  Behrens, Georg M N ^a,b,c   Stoll, Matthias ^a   Schmidt, Reinhold E ^a  

^a HANNOVER MEDICAL SCHOOL   (Germany)

^b WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH   (Australia)

^c ROYAL MELBOURNE HOSPITAL   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

CCAAT ENHANCER BINDING PROTEIN; DNA BINDING PROTEIN; FATTY ACID; SREBF1 PROTEIN, HUMAN; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; TRANSCRIPTION FACTOR; VERY LOW DENSITY LIPOPROTEIN;

ANIMAL; BLOOD; CHEMICALLY INDUCED DISORDER; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HYPERLIPIDEMIA; METABOLIC SYNDROME X; METABOLISM; PATHOPHYSIOLOGY; REVIEW;

ANIMALS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; CCAAT-ENHANCER-BINDING PROTEINS; DNA-BINDING PROTEINS; FATTY ACIDS, NONESTERIFIED; HUMANS; HYPERLIPIDEMIAS; LIPOPROTEINS, VLDL; METABOLIC SYNDROME X; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; TRANSCRIPTION FACTORS;

EID: 0242335908     PISSN: 00652326     EISSN: None     Source Type: Book Series    
DOI: 10.1159/000073177     Document Type: Article

References (69)

1. Carr A, Samaras K, Thorisdottir A, Kaufmann GR, Chisholm DJ, Cooper DA: Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: A cohort study. Lancet 1999;353:2093-2099.
2. Behrens GM, Stoll M, Schmidt RE: Lipodystrophy syndrome in HIV infection: What is it, what causes it and how can it be managed? Drug Saf 2000;23:57-76.
3. Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm DJ, et al: A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 1998;12:F51-F58.
4. Nolan D, John M, Mallal S: Antiretroviral therapy and the lipodystrophy syndrome. 2. Concepts in aetiopathogenesis. Antivir Ther 2001;6:145-160.
5. Behrens G, Dejam A, Schmidt H, Balks HJ, Brabant G, Korner T, et al: Impaired glucose tolerance, beta cell function and lipid metabolism in HIV patients under treatment with protease inhibitors. AIDS 1999;13:F63-F70.
6. Segerer S, Bogner JR, Walli R, Loch O, Goebel FD: Hyperlipidemia under treatment with proteinase inhibitors. Infection 1999;27:77-81.
7. Gervasoni C, Ridolfo AL, Trifiro G, Santambrogio S, Norbiato G, Musicco M, et al: Redistribution of body fat in HIV-infected women undergoing combined antiretroviral therapy. AIDS 1999;13:465-471.
8. Echevarria KL, Hardin TC, Smith JA: Hyperlipidemia associated with protease inhibitor therapy. Ann Pharmacother 1999;33:859-863.
9. Vigouroux C, Gharakhanian S, Salhi Y, Nguyen TH, Chevenne D, Capeau J, et al: Diabetes, insulin resistance and dyslipidaemia in lipodystrophic HIV-infected patients on highly active antiretroviral therapy (HAART). Diabetes Metab 1999;25:225-232.
10. van der Valk M, Bisschop PH, Romijn JA, Ackermans MT, Lange JM, Endert E , et al: Lipodystrophy in HIV-1-positive patients is associated with insulin resistance in multiple metabolic pathways. AIDS 2001;15:2093-2100.
11. Meininger G, Hadigan C, Laposata M, Brown J, Rabe J, Louca J, et al: Elevated concentrations of free fatty acids are associated with increased insulin response to standard glucose challenge in human immunodeficiency virus-infected subjects with fat redistribution. Metabolism 2002;51:260-266.
12. Lenhard JM, Croom DK, Weiel JE, Winegar DA: HIV protease inhibitors stimulate hepatic triglyceride synthesis. Arterioscler Thromb Vase Biol 2000;20:2625-2629.
13. Schmitz M, Michl GM, Walli R, Bogner J, Bedynek A, Seidel D, et al: Alterations of apolipoprotein B metabolism in HIV-infected patients with antiretroviral combination therapy. J Acquir Immune Defic Syndr 2001;26:225-235.
14. 13a Sekhar RV, Jahoor F, White AC, Pownall HJ, Visnegarwala F, Rodriguez-Barradas MC, Sharma M, Reeds PJ, Balasubramanyam A: Metabolic basis of HIV-lipodystrophy syndrome. Am J Physiol Endocrinol Metab 2002;283:E332-E337.
15. Baril L, Beucler I, Valantin MA, Bruckert E, Bonnefont-Rousselot D, Coutellier A, et al: Low lipolytic enzyme activity in patients with severe hypertriglyceridemia on highly active antiretroviral therapy. AIDS 2001;15:415-417.
16. Behrens G, Schmidt HH, Stoll M, Schmidt RE: ApoE genotype and protease-inhibitor-associated hyperlipidaemia. Lancet 1999;354:76.
17. Fauvel J, Bonnet E, Ruidavets JB, Ferrieres J, Toffoletti A, Massip P, et al: An interaction between apo C-III variants and protease inhibitors contributes to high triglyceride/low HDL levels in treated HIV patients. AIDS 2001;15:2397-2406.
18. Lenhard JM, Furfine ES, Jain RG, Ittoop O, Orband-Miller LA, Blanchard SG, et al: HIV protease inhibitors block adipogenesis and increase lipolysis in vitro. Antiviral Res 2000;47:121-129.
19. Ware LJ: Differences in the postprandial lipid metabolism in patients with PI-associated and NRTI-associated lipodystrophy (abstract O20.2002). 2nd Int Workshop Adverse Drug Reactions Lipodystrophy HIV, Toronto, September 2000.
20. Liang JS, Distler O, Cooper DA, Jamil H, Deckelbaum RJ, Ginsberg HN, et al: HIV protease inhibitors protect apolipoprotein B from degradation by the proteasome: A potential mechanism for protease inhibitor-induced hyperlipidemia. Nat Med 2001;7:1327-1331.
21. Kelleher AD, Sewell AK, Price DA: Dyslipidemia due to retroviral protease inhibitors. Nat Med 2002;8:308-309.
22. Riddle TM, Kuhel DG, Woollett LA, Fichtenbaum CJ, Hui DY: 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 2001;276:37514-37519.
23. Caron M, Auclair M, Vigouroux C, Glorian M, Forest C, Capeau J: The HIV protease inhibitorv indinavir impairs sterol regulatory element-binding protein-1 intranuclear localization, inhibits preadipocyte differentiation, and induces insulin resistance. Diabetes 2001;50:1378-1388.
24. Bastard JP, Caron M, Vidal H, Jan V, Auclair M, Vigouroux C, et al: 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 2002;359: 1026-1031.
25. Miserez AR, Muller PY, Barella L, Schwietert M, Erb P, Vernazza PL, et al: A single-nucleotide polymorphism in the sterol-regulatory element-binding protein 1c gene is predictive of HIVrelated hyperlipoproteinaemia. AIDS 2001;15:2045-2049.
26. Sewter C, Berger D, Considine RV, Medina G, Rochford J, Ciaraldi T, et al: Human obesity and type 2 diabetes are associated with alterations in SREBP1 isoform expression that are reproduced ex vivo by tumor necrosis factor-alpha. Diabetes 2002;51:1035-1041.
27. Christeff N, Melchior JC, de Truchis P, Perronne C, Nunez EA, Gougeon ML: Lipodystrophy defined by a clinical score in HIV-infected men on highly active antiretroviral therapy: Correlation between dyslipidaemia and steroid hormone alterations. AIDS 1999;13:2251-2260.
28. Petit JM, Duong M, Duvillard L, Florentin E, Portier H, Lizard G, et al: LDL-receptors expression in HIV-infected patients: Relations to antiretroviral therapy, hormonal status, and presence of lipodystrophy. Eur J Clin Invest 2002;32:354-359.
29. Serghides L, Nathoo S, Walmsley S, Kain KC: CD36 deficiency induced by antiretroviral therapy. AIDS 2002;16:353-358.
30. Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm DJ, et al: A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 1998;12:F51-F58.
31. Martinez E, Gatell J: Metabolic abnormalities and use of HIV-1 protease inhibitors. Lancet 1998;352:821-822.
32. Walli R, Herfort O, Michl GM, Demant T, Jager H, Dieterle C, et al: Treatment with protease inhibitors associated with peripheral insulin resistance and impaired oral glucose tolerance in HIV-1-infected patients. AIDS 1998;12:F167-F173.
33. Hadigan C, Miller K, Corcoran C, Anderson E, Basgoz N, Grinspoon S: Fasting hyperinsulinemia and changes in regional body composition in human immunodeficiency virus-infected women. J Clin Endocrinol Metab 1999;84:1932-1937.
34. Yarasheski KE, Tebas P, Sigmund C, Dagogo-Jack S, Bohrer A, Turk J, et al: Insulin resistance in HIV protease inhibitor-associated diabetes. J Acquir Immune Defic Syndr 1999;21: 209-216.
35. Hadigan C, Corcoran C, Stanley T, Piecuch S, Klibanski A, Grinspoon S: Fasting hyperinsulinemia in human immunodeficiency virus-infected men: Relationship to body composition, gonadal function, and protease inhibitor use. J Clin Endocrinol Metab 2000;85:35-41.
36. Mulligan K, Grunfeld C, Tai VW, Algren H, Pang M, Chernoff DN, et al: Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection. J Acquir Immune Defic Syndr 2000;23:35-43.
37. Dube MP: Disorders of glucose metabolism in patients infected with human immunodeficiency virus. Clin Infect Dis 2000;31:1467-1475.
38. Dube MP, Edmondson-Melancon H, Qian D, Aqeel R, Johnson D, Buchanan TA: Prospective evaluation of the effect of initiating indinavir-based therapy on insulin sensitivity and B-cell function in HIV-infected patients. J Acquir Immune Defic Syndr 2001;27:130-134.
39. Hruz PW, Murata H, Mueckler M: Adverse metabolic consequences of HIV protease inhibitor therapy: The search for a central mechanism. Am J Physiol Endocrinol Metab 2001;280: E549-E553.
40. Hruz PW, Murata H, Qiu H, Mueckler M: Indinavir induces acute and reversible peripheral insulin resistance in rats. Diabetes 2002;51:937-942.
41. Murata H, Hruz PW, Mueckler M: Indinavir inhibits the glucose transporter isoform Glut4 at physiologic concentrations. AIDS 2002;16:859-863.
42. Murata H, Hruz PW, Mueckler M: The mechanism of insulin resistance caused by HIV protease inhibitor therapy. J Biol Chem 2000;275:20251-20254.
43. Rudich A, Vanounou S, Riesenberg K, Porat M, Tirosh A, Harman-Boehm I, et al: The HIV protease inhibitor nelfinavir induces insulin resistance and increases basal lipolysis in 3T3-L1 adipocytes. Diabetes 2001;50:1425-1431.
44. Mulligan K, Grunfeld C, Tai VW, Algren H, Pang M, Chernoff DN, et al: Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection. J Acquir Immune Defic Syndr 2000;23:35-43.
45. Nolte LA, Yarasheski KE, Kawanaka K, Fisher J, Le N, Holloszy JO: The HIV protease inhibitor indinavir decreases insulin- and contraction-stimulated glucose transport in skeletal muscle. Diabetes 2001;50:1397-1401.
46. Schutt M, Meier M, Meyer M, Klein J, Aries SP, Klein HH: The HIV-1 protease inhibitor indinavir impairs insulin signalling in HepG2 hepatoma cells. Diabetologia 2000;43:1145-1148.
47. Hadigan C, Meigs JB, Corcoran C, Rietschel P, Piecuch S, Basgoz N, et al: Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy. Clin Infect Dis 2001;32:130-139.
48. Mynarcik DC, Frost RA, Lang CH, De Cristofaro K, McNurlan MA, Garlick PJ, et al: Insulin-like growth factor system in patients with HIV infection: Effect of exogenous growth hormone administration. J Acquir Immune Defic Syndr 1999;22:49-55.
49. 47a Gan SK, Samaras K, Thompson CH, Kraegen EW, Carr A, Cooper DA, Chisholm DJ: Altered myocellular and abdominal fat partitioning predict disturbance in insulin action in HIV protease inhibitor-related lipodystrophy. Diabetes 2002;51:3163-3169.
50. 47b Sutinen J, Hakkinen AM, Westerbacka J, Seppala-Lindroos A, Vehkavaara S, Halavaara J, Jarvinen A, Ristola M, Yki-Jarvinen H: Increased fat accumulation in the liver in HIV-infected patients with antiretroviral therapy-associated lipodystrophy. AIDS 2002;16:2183-2193.
51. 47c Luzi L, Perseghin G, Tambussi G, Meneghini E, Scifo P, Pagliato E, Del Maschio A, Testolin G, Lazzarin A: Intramyocellular lipid accumulation and reduced whole body lipid oxidation in HIV lipodystrophy. Am J Physiol Endocrinol Metab 2003;284:E274-E280.
52. 47d Behrens GMN, Boerner A-R, Weber K, v d Hoff J, Ockenga J, Brabant G, Schmidt RE: Impaired glucose phosphorylation and transport in skeletal muscle causes insulin resistance in HIV-1 infected patients with lipodystrophy. J Clin Invest 2002;110:1319-1327.
53. Kosmiski LA, Kuritzkes DR, Lichtenstein KA, Glueck DH, Gourley PJ, Stamm ER, et al: Fat distribution and metabolic changes are strongly correlated and energy expenditure is increased in the HIV lipodystrophy syndrome. AIDS 2001;15:1993-2000.
54. Nolan D, Mallal S: Getting to the HAART of insulin resistance. AIDS 2001;15:2037-2041.
55. Grinspoon S, Corcoran C, Miller K, Wang E, Hubbard J, Schoenfeld D, et al: Determinants of increased energy expenditure in HIV-infected women. Am J Clin Nutr 1998;68:720-725.
56. Grunfeld C, Kotler DP, Hamadeh R, Tierney A, Wang J, Pierson RN: Hypertriglyceridemia in the acquired immunodeficiency syndrome. Am J Med 1989;86:27-31.
57. Grunfeld C, Kotler DP, Shigenaga JK, Doerrler W, Tierney A, Wang J, et al: Circulating interferonalpha levels and hypertriglyceridemia in the acquired immunodeficiency syndrome. Am J Med 1991;90:154-162.
58. Hellerstein MK, Grunfeld C, Wu K, Christiansen M, Kaempfer S, Kletke C, et al: Increased de novo hepatic lipogenesis in human immunodeficiency virus infection. J Clin Endocrinol Metab 1993;76:559-565.
59. Purnell JQ, Zambon A, Knopp RH, Pizzuti DJ, Achari R, Leonard JM, et al: Effect of ritonavir on lipids and post-heparin lipase activities in normal subjects. AIDS 2000;14:51-57.
60. Hommes MJ, Romijn JA, Endert E, Eeftinck Schattenkerk JK, Sauerwein HP: Insulin sensitivity and insulin clearance in human immunodeficiency virus-infected men. Metabolism 1991; 40:651-656.
61. Heyligenberg R, Romijn JA, Hommes MJ, Endert E, Eeftinck Schattenkerk JK, Sauerwein HP: Non-insulin-mediated glucose uptake in human immunodeficiency virus-infected men. Clin Sci (Lond) 1993;84:209-216.
62. Christeff N, Melchior JC, de Truchis P, Perronne C, Gougeon ML: Increased serum interferon alpha in HIV-1 associated lipodystrophy syndrome. Eur J Clin Invest 2002;32:43-50.
63. Estrada V, Serrano-Rios M, Martinez Larrad MT, Villar NG, Gonzalez LA, Tellez MJ, et al: Leptin and adipose tissue maldistribution in HIV-infected male patients with predominant fat loss treated with antiretroviral therapy. J Acquir Immune Defic Syndr 2002;29:32-40.
64. Pernerstorfer-Schoen H, Jilma B, Perschler A, Wichlas S, Schindler K, Schindl A, et al: Sex differences in HAART-associated dyslipidaemia. AIDS 2001;15:725-734.
65. Mynarcik DC, Combs T, McNurlan MA, Scherer PE, Komaroff E, Gelato MC: Adiponectin and leptin levels in HIV-infected subjects with insulin resistance and body fat redistribution. J Acquir Immune Defic Syndr 2002;31:514-520.
66. Nagy GS, Tsiodras S, Martin LD, Avihingsanon A, Gavrila A, Hsu WC, Karchmer AW, Mantzoros CS: Human immunodeficiency virus type 1-related lipoatrophy and lipohypertrophy are associated with serum concentrations of leptin. Clin Infect Dis 2003;36:795-802.
67. Addy CL, Gavrila A, Tsiodras S, Brodovicz K, Karchmer AW, Mantzoros CS: Hypoadiponectinemia is associated with insulin resistance, hypertriglyceridemia, and fat redistribution in human immunodeficiency virus-infected patients treated with highly active antiretroviral therapy. J Clin Endocrinol Metab 2003;88:627-636.
68. Sutinen J, Korsheninnikova E, Funahashi T, Matsuzawa Y, Nyman T, Yki-Jarvinen H: Circulating concentration of adiponectin and its expression in subcutaneous adipose tissue in patients with highly active antiretroviral therapy-associated lipodystrophy. J Clin Endocrinol Metab 2003;88: 1907-1910.
69. Tong Q, Sankale JL, Hadigan CM, Tan G, Rosenberg ES, Kanki PJ, Grinspoon SK, Hotamisligil GS: Regulation of adiponectin in human immunodeficiency virus-infected patients: relationship to body composition and metabolic indices. J Clin Endocrinol Metab 2003;88:1559-1564.