Copyright © 2009 Martine Caron et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

1. M.-L. Gougeon, L. Pénicaud, B. Fromenty, P. Leclercq, J.-P. Viard, and J. Capeau, “Adipocytes targets and actors in the pathogenesis of HIV-associated lipodystrophy and metabolic alterations,” Antiviral Therapy, vol. 9, no. 2, pp. 161–177, 2004.
2. F. Villarroya, P. Domingo, and M. Giralt, “Lipodystrophy in HIV 1-infected patients: lessons for obesity research,” International Journal of Obesity, vol. 31, no. 12, pp. 1763–1776, 2007. View at Publisher · View at Google Scholar · View at PubMed
3. S. Grinspoon and A. Carr, “Cardiovascular risk and body-fat abnormalities in HIV-infected adults,” The New England Journal of Medicine, vol. 352, no. 1, pp. 48–62, 2005. View at Publisher · View at Google Scholar · View at PubMed
4. D. Nolan and S. Mallal, “Complications associated with NRTI therapy: update on clinical features and possible pathogenic mechanisms,” Antiviral Therapy, vol. 9, no. 6, pp. 849–863, 2004.
5. M. Giralt, P. Domingo, J. P. Guallar, et al., “HIV-1 infection alters gene expression in adipose tissue, which contributes to HIV-1/HAART-associated lipodystrophy,” Antiviral Therapy, vol. 11, no. 6, pp. 729–740, 2006.
6. S. Shibuyama, A. Gevorkyan, U. Yoo, S. Tim, K. Dzhangiryan, and J. D. Scott, “Understanding and avoiding antiretroviral adverse events,” Current Pharmaceutical Design, vol. 12, no. 9, pp. 1075–1090, 2006. View at Publisher · View at Google Scholar
7. M. Boyd and P. Reiss, “The long-term consequences of antiretroviral therapy: a review,” Journal of HIV Therapy, vol. 11, no. 2, pp. 26–35, 2006.
8. S. B. Haugaard, “Toxic metabolic syndrome associated with HAART,” Expert Opinion on Drug Metabolism and Toxicology, vol. 2, no. 3, pp. 429–445, 2006. View at Publisher · View at Google Scholar · View at PubMed
9. M. P. Dubé, R. A. Parker, P. Tebas, et al., “Glucose metabolism, lipid, and body fat changes in antiretroviral-naive subjects randomized to nelfinavir or efavirenz plus dual nucleosides,” AIDS, vol. 19, no. 16, pp. 1807–1818, 2005.
10. D. Podzamczer, E. Ferrer, P. Sanchez, et al., “Less lipoatrophy and better lipid profile with abacavir as compared to stavudine: 96-week results of a randomized study,” Journal of Acquired Immune Deficiency Syndromes, vol. 44, no. 2, pp. 139–147, 2007. View at Publisher · View at Google Scholar · View at PubMed
11. A.-B. E. Hansen, B. Lindegaard, N. Obel, O. Andersen, H. Nielsen, and J. Gerstoft, “Pronounced lipoatrophy in HIV-infected men receiving HAART for more than 6 years compared with the background population,” HIV Medicine, vol. 7, no. 1, pp. 38–45, 2006. View at Publisher · View at Google Scholar · View at PubMed
12. K. Mulligan, R. A. Parker, L. Komarow, et al., “Mixed patterns of changes in central and peripheral fat following initiation of antiretroviral therapy in a randomized trial,” Journal of Acquired Immune Deficiency Syndromes, vol. 41, no. 5, pp. 590–597, 2006. View at Publisher · View at Google Scholar · View at PubMed
13. D. Podzamczer, M. S. King, C. E. Klein, et al., “High-dose lopinavir/ritonavir in highly treatment-experienced HIV-1 patients: efficacy, safety, and predictors of response,” HIV Clinical Trials, vol. 8, no. 4, pp. 193–204, 2007. View at Publisher · View at Google Scholar · View at PubMed
14. R. H. Haubrich, S. Riddler, G. DiRenzo, et al., “Metabolic outcomes of ACTG 5142: a prospective, randomized, phase III trial of NRTI-, PI-, and NNRTI-sparing regimens for initial treatment of HIV-1 infection,” in Proceedings of the 14th Conference on Retroviruses and Opportunistic Infections (CROI '07), Los Angeles, Calif, USA, February 2007.
15. K. Brinkman, J. A. Smeitink, J. A. Romijn, and P. Reiss, “Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy,” The Lancet, vol. 354, no. 9184, pp. 1112–1115, 1999. View at Publisher · View at Google Scholar
16. W. Lewis, B. J. Day, and W. C. Copeland, “Mitochondrial toxicity of NRTI antiviral drugs: an integrated cellular perspective,” Nature Reviews Drug Discovery, vol. 2, no. 10, pp. 812–822, 2003. View at Publisher · View at Google Scholar · View at PubMed
17. M. Caron, M. Auclair, C. Lagathu, et al., “The HIV-1 nucleoside reverse transcriptase inhibitors stavudine and zidovudine alter adipocyte functions in vitro,” AIDS, vol. 18, no. 16, pp. 2127–2136, 2004. View at Publisher · View at Google Scholar
18. U. A. Walker, M. Auclair, D. Lebrecht, M. Kornprobst, J. Capeau, and M. Caron, “Uridine abrogates the adverse effects of antiretroviral pyrimidine analogues on adipose cell functions,” Antiviral Therapy, vol. 11, no. 1, pp. 25–34, 2006.
19. M. Caron, M. Auclair, A. Vissian, C. Vigouroux, and J. Capeau, “Contribution of mitochondrial dysfunction and oxidative stress to cellular premature senescence induced by antiretroviral thymidine analogues,” Antiviral Therapy, vol. 13, no. 1, pp. 27–38, 2008.
20. P. Dowell, C. Flexner, P. O. Kwiterovich, and M. D. Lane, “Suppression of preadipocyte differentiation and promotion of adipocyte death by HIV protease inhibitors,” The Journal of Biological Chemistry, vol. 275, no. 52, pp. 41325–41332, 2000. View at Publisher · View at Google Scholar · View at PubMed
21. M. Caron, M. Auclair, C. Vigouroux, M. Glorian, C. Forest, and J. Capeau, “The HIV protease inhibitor indinavir impairs sterol regulatory element-binding protein-1 intranuclear localization, inhibits preadipocyte differentiation, and induces insulin resistance,” Diabetes, vol. 50, no. 6, pp. 1378–1388, 2001. View at Publisher · View at Google Scholar
22. M. Caron, M. Auclair, H. Sterlingot, M. Kornprobst, and J. Capeau, “Some HIV protease inhibitors alter lamin A/C maturation and stability, SREBP-1 nuclear localization and adipocyte differentiation,” AIDS, vol. 17, no. 17, pp. 2437–2444, 2003. View at Publisher · View at Google Scholar
23. C. Lagathu, J.-P. Bastard, M. Auclair, et al., “Antiretroviral drugs with adverse effects on adipocyte lipid metabolism and survival alter the expression and secretion of proinflammatory cytokines and adiponectin in vitro,” Antiviral Therapy, vol. 9, no. 6, pp. 911–920, 2004.
24. C. Vernochet, S. Azoulay, D. Duval, et al., “Human immunodeficiency virus protease inhibitors accumulate into cultured human adipocytes and alter expression of adipocytokines,” The Journal of Biological Chemistry, vol. 280, no. 3, pp. 2238–2243, 2005. View at Publisher · View at Google Scholar · View at PubMed
25. M. Pacenti, L. Barzon, F. Favaretto, et al., “Microarray analysis during adipogenesis identifies new genes altered by antiretroviral drugs,” AIDS, vol. 20, no. 13, pp. 1691–1705, 2006. View at Publisher · View at Google Scholar · View at PubMed
26. S. Viengchareun, M. Caron, M. Auclair, et al., “Mitochondrial toxicity of indinavir, stavudine and zidovudine involves multiple cellular targets in white and brown adipocytes,” Antiviral Therapy, vol. 12, no. 6, pp. 919–929, 2007.
27. R. Ben-Romano, A. Rudich, D. Török, et al., “Agent and cell-type specificity in the induction of insulin resistance by HIV protease inhibitors,” AIDS, vol. 17, no. 1, pp. 23–32, 2003. View at Publisher · View at Google Scholar
28. A. Rudich, R. Ben-Romano, S. Etzion, and N. Bashan, “Cellular mechanisms of insulin resistance, lipodystrophy and atherosclerosis induced by HIV protease inhibitors,” Acta Physiologica Scandinavica, vol. 183, no. 1, pp. 75–88, 2005. View at Publisher · View at Google Scholar · View at PubMed
29. P. Domingo, X. Matias-Guiu, R. M. Pujol, et al., “Subcutaneous adipocyte apoptosis in HIV-1 protease inhibitor-associated lipodystrophy,” AIDS, vol. 13, no. 16, pp. 2261–2267, 1999. View at Publisher · View at Google Scholar
30. J. P. Bastard, C. Lagathu, M. Maachi, et al., “Adipose tissue cytokines and insulin resistance,” Journées Annuelles de Diabétologie de l'Hôtel-Dieu, pp. 29–37, 2004 (French).
31. C. Lagathu, M. Kim, M. Maachi, et al., “HIV antiretroviral treatment alters adipokine expression and insulin sensitivity of adipose tissue in vitro and in vivo,” Biochimie, vol. 87, no. 1, pp. 65–71, 2005. View at Publisher · View at Google Scholar · View at PubMed
32. S. P. Jones, O. Janneh, D. J. Back, and M. Pirmohamed, “Altered adipokine response in murine 3T3-F442A adipocytes treated with protease inhibitors and nucleoside reverse transcriptase inhibitors,” Antiviral Therapy, vol. 10, no. 2, pp. 207–213, 2005.
33. C. Lagathu, B. Eustace, M. Prot, et al., “Some HIV antiretrovirals increase oxidative stress and alter chemokine, cytokine or adiponectin production in human adipocytes and macrophages,” Antiviral Therapy, vol. 12, no. 4, pp. 489–500, 2007.
34. M. Caron, M. Auclair, B. Donadille, et al., “Human lipodystrophies linked to mutations in A-type lamins and to HIV protease inhibitor therapy are both associated with prelamin A accumulation, oxidative stress and premature cellular senescence,” Cell Death and Differentiation, vol. 14, no. 10, pp. 1759–1767, 2007. View at Publisher · View at Google Scholar · View at PubMed
35. R. Ben-Romano, A. Rudich, S. Etzion, et al., “Nelfinavir induces adipocyte insulin resistance through the induction of oxidative stress: differential protective effect of antioxidant agents,” Antiviral Therapy, vol. 11, no. 8, pp. 1051–1060, 2006.
36. J.-P. Bastard, M. Caron, H. Vidal, 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,” The Lancet, vol. 359, no. 9311, pp. 1026–1031, 2002. View at Publisher · View at Google Scholar · View at PubMed
37. V. Jan, P. Cervera, M. Maachi, et al., “Altered fat differentiation and adipocytokine expression are inter-related and linked to morphological changes and insulin resistance in HIV-1-infected lipodystrophic patients,” Antiviral Therapy, vol. 9, no. 4, pp. 555–564, 2004.
38. D. Nolan, E. Hammond, A. Martin, et al., “Mitochondrial DNA depletion and morphologic changes in adipocytes associated with nucleoside reverse transcriptase inhibitor therapy,” AIDS, vol. 17, no. 9, pp. 1329–1338, 2003. View at Publisher · View at Google Scholar
39. C. L. Cherry, L. Lal, K. A. Thompson, et al., “Increased adipocyte apoptosis in lipoatrophy improves within 48 weeks of switching patient therapy from stavudine to abacavir or zidovudine,” Journal of Acquired Immune Deficiency Syndromes, vol. 38, no. 3, pp. 263–267, 2005.
40. P. Domingo, F. Vidal, J. C. Domingo, et al., “Tumour necrosis factor alpha in fat redistribution syndromes associated with combination antiretroviral therapy in HIV-1-infected patients: potential role in subcutaneous adipocyte apoptosis,” European Journal of Clinical Investigation, vol. 35, no. 12, pp. 771–780, 2005. View at Publisher · View at Google Scholar · View at PubMed
41. S. R. Farmer, “Regulation of PPAR$\gamma$ activity during adipogenesis,” International Journal of Obesity, vol. 29, pp. S13–S16, 2005. View at Publisher · View at Google Scholar · View at PubMed
42. U. Kintscher and R. E. Law, “PPAR$\gamma$-mediated insulin sensitization: the importance of fat versus muscle,” American Journal of Physiology, vol. 288, no. 2, pp. E287–E291, 2005. View at Publisher · View at Google Scholar · View at PubMed
43. G. Medina-Gomez, S. L. Gray, L. Yetukuri, et al., “PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism,” PLoS Genetics, vol. 3, no. 4, p. e64, 2007. View at Publisher · View at Google Scholar · View at PubMed
44. D. B. Savage, “PPAR$\gamma$ as a metabolic regulator: insights from genomics and pharmacology,” Expert Reviews in Molecular Medicine, vol. 7, no. 1, pp. 1–16, 2005. View at Publisher · View at Google Scholar · View at PubMed
45. R. K. Semple, V. K. K. Chatterjee, and S. O'Rahilly, “PPAR$\gamma$ and human metabolic disease,” The Journal of Clinical Investigation, vol. 116, no. 3, pp. 581–589, 2006. View at Publisher · View at Google Scholar · View at PubMed
46. R. M. Touyz and E. L. Schiffrin, “Peroxisome proliferator-activated receptors in vascular biology-molecular mechanisms and clinical implications,” Vascular Pharmacology, vol. 45, no. 1, pp. 19–28, 2006. View at Publisher · View at Google Scholar · View at PubMed
47. S. Heikkinen, J. Auwerx, and C. A. Argmann, “PPAR$\gamma$ in human and mouse physiology,” Biochimica et Biophysica Acta, vol. 1771, no. 8, pp. 999–1013, 2007. View at Publisher · View at Google Scholar · View at PubMed
48. L. Casteilla, B. Cousin, and M. Carmona, “PPARs and adipose cell plasticity,” PPAR Research, vol. 2007, Article ID 68202, 7 pages, 2007. View at Publisher · View at Google Scholar · View at PubMed
49. S. R. Farmer, “Molecular determinants of brown adipocyte formation and function,” Genes & Development, vol. 22, no. 10, pp. 1269–1275, 2008. View at Publisher · View at Google Scholar · View at PubMed
50. J. I. Odegaard, R. R. Ricardo-Gonzalez, M. H. Goforth, et al., “Macrophage-specific PPAR$\gamma$ controls alternative activation and improves insulin resistance,” Nature, vol. 447, no. 7148, pp. 1116–1120, 2007. View at Publisher · View at Google Scholar · View at PubMed
51. E. Rigamonti, G. Chinetti-Gbaguidi, and B. Staels, “Regulation of macrophage functions by PPAR-$\alpha$, PPAR-$\gamma$, and LXRs in mice and men,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 6, pp. 1050–1059, 2008. View at Publisher · View at Google Scholar · View at PubMed
52. V. Planat-Benard, J.-S. Silvestre, B. Cousin, et al., “Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives,” Circulation, vol. 109, no. 5, pp. 656–663, 2004. View at Publisher · View at Google Scholar · View at PubMed
53. K. Z. Al-Shali, A. A. House, A. J. G. Hanley, H. M. R. Khan, and S. B. Harris, “Genetic variation in PPARG encoding peroxisome proliferator-activated receptor $\gamma$ associated with carotid atherosclerosis,” Stroke, vol. 35, no. 9, pp. 2036–2040, 2004. View at Publisher · View at Google Scholar · View at PubMed
54. A. C. Li and W. Palinski, “Peroxisome proliferator-activated receptors: how their effects on macrophages can lead to the development of a new drug therapy against atherosclerosis,” Annual Review of Pharmacology and Toxicology, vol. 46, pp. 1–39, 2006. View at Publisher · View at Google Scholar · View at PubMed
55. S. Z. Duan, C. Y. Ivashchenko, S. E. Whitesall, et al., “Hypotension, lipodystrophy, and insulin resistance in generalized PPAR$\gamma$-deficient mice rescued from embryonic lethality,” The Journal of Clinical Investigation, vol. 117, no. 3, pp. 812–822, 2007. View at Publisher · View at Google Scholar · View at PubMed
56. S. Kim, L.-W. Huang, K. J. Snow, et al., “A mouse model of conditional lipodystrophy,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 42, pp. 16627–16632, 2007. View at Publisher · View at Google Scholar · View at PubMed
57. K. Reue and J. Phan, “Metabolic consequences of lipodystrophy in mouse models,” Current Opinion in Clinical Nutrition and Metabolic Care, vol. 9, no. 4, pp. 436–441, 2006. View at Publisher · View at Google Scholar · View at PubMed
58. R. L. Boguslavsky, C. L. Stewart, and H. J. Worman, “Nuclear lamin A inhibits adipocyte differentiation: implications for Dunnigan-type familial partial lipodystrophy,” Human Molecular Genetics, vol. 15, no. 4, pp. 653–663, 2006. View at Publisher · View at Google Scholar · View at PubMed
59. C. Capanni, E. Mattioli, M. Columbaro, et al., “Altered pre-lamin A processing is a common mechanism leading to lipodystrophy,” Human Molecular Genetics, vol. 14, no. 11, pp. 1489–1502, 2005. View at Publisher · View at Google Scholar · View at PubMed
60. V. A. Payne, N. Grimsey, A. Tuthill, et al., “The human lipodystrophy gene BSCL2/seipin may be essential for normal adipocyte differentiation,” Diabetes, vol. 57, no. 8, pp. 2055–2060, 2008. View at Publisher · View at Google Scholar · View at PubMed
61. B. Zhang, K. MacNaul, D. Szalkowski, Z. Li, J. Berger, and D. E. Moller, “Inhibition of adipocyte differentiation by HIV protease inhibitors,” The Journal of Clinical Endocrinology & Metabolism, vol. 84, no. 11, pp. 4274–4277, 1999.
62. D. Mondal, V. F. Larussa, and K. C. Agrawal, “Synergistic antiadipogenic effects of HIV type 1 protease inhibitors with tumor necrosis factor $\alpha$: suppression of extracellular insulin action mediated by extracellular matrix-degrading proteases,” AIDS Research and Human Retroviruses, vol. 17, no. 17, pp. 1569–1584, 2001. View at Publisher · View at Google Scholar · View at PubMed
63. R. Roche, I. Poizot-Martin, C. M.-E. Yazidi, et al., “Effects of antiretroviral drug combinations on the differentiation of adipocytes,” AIDS, vol. 16, no. 1, pp. 13–20, 2002. View at Publisher · View at Google Scholar
64. C. Vernochet, S. Azoulay, D. Duval, R. Guedj, G. Ailhaud, and C. Dani, “Differential effect of HIV protease inhibitors on adipogenesis: intracellular ritonavir is not sufficient to inhibit differentiation,” AIDS, vol. 17, no. 15, pp. 2177–2180, 2003. View at Publisher · View at Google Scholar
65. P. Dowell and M. D. Lane, “C/EBP$\alpha$ reverses the anti-adipogenic effects of the HIV protease inhibitor nelfinavir,” Biochemical and Biophysical Research Communications, vol. 327, no. 2, pp. 571–574, 2005. View at Publisher · View at Google Scholar · View at PubMed
66. B. A. Kudlow, S. A. Jameson, and B. K. Kennedy, “HIV protease inhibitors block adipocyte differentiation independently of lamin A/C,” AIDS, vol. 19, no. 15, pp. 1565–1573, 2005. View at Publisher · View at Google Scholar
67. R. J. Kim, C. G. Wilson, M. Wabitsch, M. A. Lazar, and C. M. Steppan, “HIV protease inhibitor-specific alterations in human adipocyte differentiation and metabolism,” Obesity, vol. 14, no. 6, pp. 994–1002, 2006. View at Publisher · View at Google Scholar · View at PubMed
68. S. Grigem, P. Fischer-Posovszky, K. M. Debatin, E. Loizon, H. Vidal, and M. Wabitsch, “The effect of the HIV protease inhibitor ritonavir on proliferation, differentiation, lipogenesis, gene expression and apoptosis of human preadipocytes and adipocytes,” Hormone and Metabolic Research, vol. 37, no. 10, pp. 602–609, 2005. View at Publisher · View at Google Scholar · View at PubMed
69. M. A. Noor, O. P. Flint, J.-F. Maa, and R. A. Parker, “Effects of atazanavir/ritonavir and lopinavir/ritonavir on glucose uptake and insulin sensitivity: demonstrable differences in vitro and clinically,” AIDS, vol. 20, no. 14, pp. 1813–1821, 2006. View at Publisher · View at Google Scholar · View at PubMed
70. M. J. Carper, W. T. Cade, M. Cam, et al., “HIV-protease inhibitors induce expression of suppressor of cytokine signaling-1 in insulin-sensitive tissues and promote insulin resistance and type 2 diabetes mellitus,” American Journal of Physiology, vol. 294, no. 3, pp. E558–E567, 2008. View at Publisher · View at Google Scholar · View at PubMed
71. S. De Barros, A. Zakaroff-Girard, M. Lafontan, J. Galitzky, and V. Bourlier, “Inhibition of human preadipocyte proteasomal activity by HIV protease inhibitors or specific inhibitor lactacystin leads to a defect in adipogenesis, which involves matrix metalloproteinase-9,” Journal of Pharmacology and Experimental Therapeutics, vol. 320, no. 1, pp. 291–299, 2007. View at Publisher · View at Google Scholar · View at PubMed
72. C. Saillan-Barreau, O. Tabbakh, J.-P. Chavoin, L. Casteilla, and L. Pénicaud, “Drug-specific effect of nelfinavir and stavudine on primary culture of human preadipocytes,” Journal of Acquired Immune Deficiency Syndromes, vol. 48, no. 1, pp. 20–25, 2008. View at Publisher · View at Google Scholar · View at PubMed
73. H. Murata, P. W. Hruz, and M. Mueckler, “The mechanism of insulin resistance caused by HIV protease inhibitor therapy,” The Journal of Biological Chemistry, vol. 275, no. 27, pp. 20251–20254, 2000. View at Publisher · View at Google Scholar · View at PubMed
74. R. Ben-Romano, A. Rudich, A. Tirosh, et al., “Nelfinavir-induced insulin resistance is associated with impaired plasma membrane recruitment of the PI 3-kinase effectors Akt/PKB and PKC-$\zeta$,” Diabetologia, vol. 47, no. 6, pp. 1107–1117, 2004. View at Publisher · View at Google Scholar · View at PubMed
75. D. V. Erbe, K. Gartrell, Y.-L. Zhang, et al., “Molecular activation of PPAR$\gamma$ by angiotensin II type 1-receptor antagonists,” Vascular Pharmacology, vol. 45, no. 3, pp. 154–162, 2006. View at Publisher · View at Google Scholar · View at PubMed
76. M. A. Noor, R. A. Parker, E. O'Mara, et al., “The effects of HIV protease inhibitors atazanavir and lopinavir/ritonavir on insulin sensitivity in HIV-seronegative healthy adults,” AIDS, vol. 18, no. 16, pp. 2137–2144, 2004. View at Publisher · View at Google Scholar
77. A. M. Umpleby, S. Das, M. Stolinski, et al., “Low density lipoprotein apolipoprotein B metabolism in treatment-naive HIV patients and patients on antiretroviral therapy,” Antiviral Therapy, vol. 10, no. 5, pp. 663–670, 2005.
78. C. Coffinier, S. E. Hudon, E. A. Farber, et al., “HIV protease inhibitors block the zinc metalloproteinase ZMPSTE24 and lead to an accumulation of prelamin A in cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 33, pp. 13432–13437, 2007. View at Publisher · View at Google Scholar · View at PubMed
79. D. J. Lloyd, R. C. Trembath, and S. Shackleton, “A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies,” Human Molecular Genetics, vol. 11, no. 7, pp. 769–777, 2002. View at Publisher · View at Google Scholar
80. G. M. N. Behrens, D. Lloyd, H. H.-J. Schmidt, R. E. Schmidt, and R. C. Trembath, “Lessons from lipodystrophy: LMNA, encoding lamin A/C, in HIV therapy-associated lipodystrophy,” AIDS, vol. 14, no. 12, pp. 1854–1855, 2000. View at Publisher · View at Google Scholar
81. L. A. Kosmiski, H. L. Miller, and D. J. Klemm, “In combination, nucleoside reverse transcriptase inhibitors have significant effects on 3T3-L1 adipocyte lipid accumulation and survival,” Antiviral Therapy, vol. 11, no. 2, pp. 187–195, 2006.
82. M. V. Stankov, T. Lücke, A. M. Das, R. E. Schmidt, and G. M. N. Behrens, “Relationship of mitochondrial DNA depletion and respiratory chain activity in preadipocytes treated with nucleoside reverse transcriptase inhibitors,” Antiviral Therapy, vol. 12, no. 2, pp. 205–216, 2007.
83. P. Puigserver, “Tissue-specific regulation of metabolic pathways through the transcriptional coactivator PGC1-$\alpha$,” International Journal of Obesity, vol. 29, pp. 5–9, 2005. View at Publisher · View at Google Scholar · View at PubMed
84. I. Pagel-Langenickel, J. Bao, J. J. Joseph, et al., “PGC-1$\alpha$ integrates insulin signaling, mitochondrial regulation, and bioenergetic function in skeletal muscle,” The Journal of Biological Chemistry, vol. 283, no. 33, pp. 22464–22472, 2008. View at Publisher · View at Google Scholar · View at PubMed
85. K. El Hadri, M. Glorian, C. Monsempes, et al., “In vitro suppression of the lipogenic pathway by the nonnucleoside reverse transcriptase inhibitor efavirenz in 3T3 and human preadipocytes or adipocytes,” The Journal of Biological Chemistry, vol. 279, no. 15, pp. 15130–15141, 2004. View at Publisher · View at Google Scholar · View at PubMed
86. T. M. Riddle, D. G. Kuhel, L. A. Woollett, C. J. Fichtenbaum, and D. Y. Hui, “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,” The Journal of Biological Chemistry, vol. 276, no. 40, pp. 37514–37519, 2001. View at Publisher · View at Google Scholar · View at PubMed
87. M. A. M. den Boer, J. F. P. Berbée, P. Reiss, et al., “Ritonavir impairs lipoprotein lipase-mediated lipolysis and decreases uptake of fatty acids in adipose tissue,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 26, no. 1, pp. 124–129, 2006. View at Publisher · View at Google Scholar · View at PubMed
88. E. S. Goetzman, L. Tian, T. R. Nagy, et al., “HIV protease inhibitor ritonavir induces lipoatrophy in male mice,” AIDS Research and Human Retroviruses, vol. 19, no. 12, pp. 1141–1150, 2003. View at Publisher · View at Google Scholar · View at PubMed
89. M. Prot, L. Heripret, N. Cardot-Leccia, et al., “Long-term treatment with lopinavir-ritonavir induces a reduction in peripheral adipose depots in mice,” Antimicrobial Agents and Chemotherapy, vol. 50, no. 12, pp. 3998–4004, 2006. View at Publisher · View at Google Scholar · View at PubMed
90. P. W. G. Mallon, P. Unemori, R. Sedwell, et al., “In vivo, nucleoside reverse-transcriptase inhibitors alter expression of both mitochondrial and lipid metabolism genes in the absence of depletion of mitochondrial DNA,” Journal of Infectious Diseases, vol. 191, no. 10, pp. 1686–1696, 2005. View at Publisher · View at Google Scholar · View at PubMed
91. K. Kannisto, J. Sutinen, E. Korsheninnikova, et al., “Expression of adipogenic transcription factors, peroxisome proliferator-activated receptor gamma co-activator 1, IL-6 and CD45 in subcutaneous adipose tissue in lipodystrophy associated with highly active antiretroviral therapy,” AIDS, vol. 17, no. 12, pp. 1753–1762, 2003. View at Publisher · View at Google Scholar
92. S. P. Jones, N. Qazi, J. Morelese, et al., “Assessment of adipokine expression and mitochondrial toxicity in HIV patients with lipoatrophy on stavudine-and zidovudine-containing regimens,” Journal of Acquired Immune Deficiency Syndromes, vol. 40, no. 5, pp. 565–572, 2005. View at Publisher · View at Google Scholar
93. C. S. Pace, A. M. Martin, E. L. Hammond, C. D. Mamotte, D. A. Nolan, and S. A. Mallal, “Mitochondrial proliferation, DNA depletion and adipocyte differentiation in subcutaneous adipose tissue of HIV-positive HAART recipients,” Antiviral Therapy, vol. 8, no. 4, pp. 323–331, 2003.
94. J. Chaparro, D. N. Reeds, W. Wen, et al., “Alterations in thigh subcutaneous adipose tissue gene expression in protease inhibitor-based highly active antiretroviral therapy,” Metabolism, vol. 54, no. 5, pp. 561–567, 2005. View at Publisher · View at Google Scholar · View at PubMed
95. M. J. Kim, P. Leclercq, E. Lanoy, et al., “A 6-month interruption of antiretroviral therapy improves adipose tissue function in HIV-infected patients: the ANRS EP29 Lipostop Study,” Antiviral Therapy, vol. 12, no. 8, pp. 1273–1283, 2007.
96. C. Vigouroux, M. Maachi, T.-H. Nguyen, et al., “Serum adipocytokines are related to lipodystrophy and metabolic disorders in HIV-infected men under antiretroviral therapy,” AIDS, vol. 17, no. 10, pp. 1503–1511, 2003. View at Publisher · View at Google Scholar
97. J. Sutinen, K. Kannisto, E. Korsheninnikova, et al., “Effects of rosiglitazone on gene expression in subcutaneous adipose tissue in highly active antiretroviral therapy-associated lipodystrophy,” American Journal of Physiology, vol. 286, no. 6, pp. E941–E949, 2004. View at Publisher · View at Google Scholar · View at PubMed
98. L. Slama, E. Lanoy, M.-A. Valantin, et al., “Effect of pioglitazone on HIV-1-related lipodystrophy: a randomized double-blind placebo-controlled trial (ANRS 113),” Antiviral Therapy, vol. 13, no. 1, pp. 67–76, 2008.
99. J. P. Guallar, J. M. Gallego-Escuredo, J. C. Domingo, et al., “Differential gene expression indicates that ‘buffalo hump’ is a distinct adipose tissue disturbance in HIV-1-associated lipodystrophy,” AIDS, vol. 22, no. 5, pp. 575–584, 2008. View at Publisher · View at Google Scholar · View at PubMed
100. M. L. Rodríguez de la Concepción, P. Yubero, J. C. Domingo, et al., “Reverse transcriptase inhibitors alter uncoupling protein-1 and mitochondrial biogenesis in brown adipocytes,” Antiviral Therapy, vol. 10, no. 4, pp. 515–526, 2005.
101. J. Nedergaard, T. Bengtsson, and B. Cannon, “Unexpected evidence for active brown adipose tissue in adult humans,” American Journal of Physiology, vol. 293, no. 2, pp. E444–E452, 2007. View at Publisher · View at Google Scholar · View at PubMed
102. L. K. Heilbronn and L. V. Campbell, “Adipose tissue macrophages, low grade inflammation and insulin resistance in human obesity,” Current Pharmaceutical Design, vol. 14, no. 12, pp. 1225–1230, 2008. View at Publisher · View at Google Scholar
103. J. Dressman, J. Kincer, S. V. Matveev, et al., “HIV protease inhibitors promote atherosclerotic lesion formation independent of dyslipidemia by increasing CD36-dependent cholesteryl ester accumulation in macrophages,” The Journal of Clinical Investigation, vol. 111, no. 3, pp. 389–397, 2003. View at Publisher · View at Google Scholar