Cellular mechanisms of lipodystrophy induction by HIV protease inhibitors

Bibliography

• Sklar P, Masur H: HIV Infection and cardiovascular disease-is there really a link? N. Engl. J. Med. 349, 2065–2067 (2003)
   Google Scholar
• Holmberg Greenberg AE, Friis-Moller N, Sabin C et al.: Trends in rates of myocardial infarction among patients with HIV. N. Engl. J. Med. 350, 730–732 (2004)
   Google Scholar
• Carr A, Samaras K, Burton S et al.: A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 12, F51–F58 (1998)
   Google Scholar
• 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. 280, E549–E553 (2001)
   Google Scholar
• Zhou H, Pandak WM Jr, Lyall V, Natarajan R, Hylemon PB: HIV protease inhibitors activate the unfolded protein response in macrophages: implication for atherosclerosis and cardiovascular disease. Mol. Pharmacol. 68, 690–700 (2005).
   Google Scholar
• First demonstration that HIV protease inhibitors (PIs) activate the uncoupling protein response (UPR) in macrophages.
   Google Scholar
• Parker RA, Flint OP, Mulvey R et al.: Endoplasmic reticulum stress links dyslipidemia to inhibition of proteasome activity and glucose transport by HIV protease inhibitors. Mol. Pharmacol. 67, 1909–1919 (2005).
   Google Scholar
• First report that HIV PI-induced inhibition of proteasome activity is related to endoplasmic reticulum (ER) stress response in hepatocytes and adipocytes.
   Google Scholar
• Fontas E, van LF, Sabin CA et al.: Lipid profiles in HIV-infected patients receiving combination antiretroviral therapy: are different antiretroviral drugs associated with different lipid profiles? J. Infect. Dis. 189, 1056–1074 (2004)
   Google Scholar
• Grover SA, Coupal L, Gilmore N, Mukherjee J: Impact of dyslipidemia associated with highly active antiretroviral therapy (HAART) on cardiovascular risk and life expectancy. Am. J. Cardiol. 95, 586–591 (2005)
   Google Scholar
• Gazzard BG, Moyle G: Does atazanavir cause lipodystrophy? J. HIV Ther. 9, 41–44 (2004)
   Google Scholar
• Hicks C, King MS, Gulick RM et al.: Long-term safety and durable antiretroviral activity of lopinavir/ritonavir in treatmentnaive patients: 4 year follow-up study. AIDS 18, 775–779 (2004)
   Google Scholar
• Benson CA, Deeks SG, Brun SC et al.: Safety and antiviral activity at 48 weeks of lopinavir/ritonavir plus nevirapine and 2 nucleoside reverse-transcriptase inhibitors in human immunodeficiency virus type 1- infected protease inhibitor-experienced patients. J. Infect. Dis. 185, 599–607 (2002)
   Google Scholar
• Murphy RL, Brun S, Hicks C et al.: ABT-378/ritonavir plus stavudine and lamivudine for the treatment of antiretroviralnaïve adults with HIV-1 infection: 48-week results. AIDS 15, F1–F9 (2001)
   Google Scholar
• Clevenbergh P, Garraffo R, Dellamonica P: Impact of various antiretroviral drugs and their plasma concentrations on plasma lipids in heavily pretreated HIV-infected patients. HIV Clin. Trials 4, 330–336 (2003)
   Google Scholar
• Murphy RL, Sanne I, Cahn P et al.: Dose-ranging, randomized, clinical trial of atazanavir with lamivudine and stavudine in antiretroviral-naive subjects: 48-week results. AIDS 17, 2603–2614 (2003)
   Google Scholar
• James JS: Lipodystrophy: Glaxo researchers suggest mechanisms, publish data. AIDS Treat. News 1–4 (1999)
   Google Scholar
• James JS: Amprenavir, new protease inhibitor, approved. AIDS Treat. News 1–3 (1999)
   Google Scholar
• Arvieux C, Tribut O: Amprenavir or fosamprenavir plus ritonavir in HIV infection: pharmacology, efficacy and tolerability profile. Drugs 65, 633–659 (2005)
   Google Scholar
• Orrick JJ, Steinhart CR: Atazanavir. Ann. Pharmacother. 38, 1664–1674 (2004)
   Google Scholar
• Cahn PE, Gatell JM, Squires K et al.: Atazanavir-a once-daily HIV protease inhibitor that does not cause dyslipidemia in newly treated patients: results from two randomized clinical trials. J. Int. Assoc. Physicians AIDS Care (Chic.Ill.) 3, 92–98 (2004)
   Google Scholar
• Havlir DV, O'Marro SD: Atazanavir: New option for treatment of HIV Infection. Clin. Infect. Dis. 38, 1599–1604 (2004)
   Google Scholar
• Rao RV, Ellerby HM, Bredesen DE: Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ. 11, 372–380 (2004).
   Google Scholar
• Good review of ER stress and apoptosis.
   Google Scholar
• Shen X, Zhang K, Kaufman RJ: The unfolded protein response-a stress signaling pathway of the endoplasmic reticulum. J. Chem. Neuroanat. 28, 79–92 (2004)
   Google Scholar
• Kaufman RJ: Orchestrating the unfolded protein response in health and disease. J. Clin. Invest. 110, 1389–1398 (2002).
   Google Scholar
• Summary of recent findings related to the UPR in human disease.
   Google Scholar
• Kaufman RJ: Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev. 13, 1211–1233 (1999)
   Google Scholar
• Welihinda AA, Tirasophon W, Kaufman RJ: The cellular response to protein misfolding in the endoplasmic reticulum. Gene Expr. 7, 293–300 (1999)
   Google Scholar
• Zhang K, Kaufman RJ: Signaling the unfolded protein response from the endoplasmic reticulum. J. Biol.Chem. 279, 25935–25938 (2004).
   Google Scholar
• Summary of signaling pathways involved in the ER stress response.
   Google Scholar
• Rutkowski DT, Kaufman RJ: A trip to the ER: coping with stress. Trends Cell Biol. 14, 20–28 (2004)
   Google Scholar
• Kaneko M, Nomura Y: ER signaling in unfolded protein response. Life Sci. 74, 199–205 (2003)
   Google Scholar
• Schroder M, Kaufman RJ: ER stress and the unfolded protein response. Mutat. Res. 569, 29–63 (2005)
   Google Scholar
• Carr A: HIV protease inhibitor-related lipodystrophy syndrome. Clin. Infect. Dis. 30(Suppl. 2), S135–S142 (2000)
   Google Scholar
• 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. 276, 37514–37519 (2001)
   Google Scholar
• Liang JS, Distler O, Cooper DA et al.: HIV protease inhibitors protect apolipoprotein B from degradation by the proteasome: a potential mechanism for protease inhibitor-induced hyperlipidemia. Nature Med. 7, 1327–1331 (2001).
   Google Scholar
• First demonstration that inhibition of the proteasome activity by HIV PIs represents a potential mechanism for HIV PI-induced hyperlipidemia.
   Google Scholar
• Tran H, Robinson S, Mikhailenko I, Strickland DK: Modulation of the LDL receptor and LRP levels by HIV protease inhibitors. J. Lipid Res. 44, 1859–1869 (2003)
   Google Scholar
• Williams K, Rao YP, Natarajan R, Pandak WM, Hylemon PB: Indinavir alters sterol and fatty acid homeostatic mechanisms in primary rat hepatocytes by increasing levels of activated sterol regulatory element-binding proteins and decreasing cholesterol 7 -hydroxylase mRNA levels. Biochem. Pharmacol. 67, 255–267 (2004).
   Google Scholar
• First demonstration that the HIV PI indinavir affects lipid homeostasis by modulating sterol regulatory element binding protein (SREBP) and cholesterol- 7-hydroxylase (CYP7A1) expression in primary hepatocytes.
   Google Scholar
• Horton JD, Goldstein JL, Brown MS: SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J. Clin. Invest. 109, 1125–1131 (2002)
   Google Scholar
• Sutinen J, Hakkinen AM, Westerbacka J et al.: Increased fat accumulation in the liver in HIV-infected patients with antiretroviral therapy-associated lipodystrophy. AIDS 16, 2183–2193 (2002)
   Google Scholar
• Haugaard SB, Andersen O, Dela F et al.: Defective glucose and lipid metabolism in human immunodeficiency virus-infected patients with lipodystrophy involve liver, muscle tissue and pancreatic {beta}-cells. Eur. J. Endocrinol. 152, 103–112 (2005)
   Google Scholar
• Linton MF, Fazio S: Macrophages, inflammation, and atherosclerosis. Int. J. Obes. Relat. Metab. Disord. 27(Suppl. 3), S35–S40, (2003)
   Google Scholar
• de Winther MP, Hofker MH: Scavenging new insights into atherogenesis. J. Clin. Invest. 105, 1039–1041 (2000)
   Google Scholar
• Kockx MM: Apoptosis in the atherosclerotic plaque: quantitative and qualitative aspects. Arterioscler. Thromb. Vasc. Biol. 18, 1519–1522 (1998)
   Google Scholar
• Martinet W, Kockx MM: Apoptosis in atherosclerosis: focus on oxidized lipids and inflammation. Curr. Opin. Lipidol. 12, 535–541 (2001)
   Google Scholar
• Feng B, Tabas I: ABCA1-mediated cholesterol efflux is defective in free cholesterol-loaded macrophages. Mechanism involves enhanced ABCA1 degradation in a process requiring full NPC1 activity. J. Biol. Chem. 277, 43271–43280 (2002)
   Google Scholar
• Feng B, Yao PM, Li Y et al.: The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nature Cell Biol. 5, 781–792 (2003).
   Google Scholar
• First demonstration that accumulation of free cholesterol in ER activates the UPR and induces apoptosis in macrophages.
   Google Scholar
• Dressman J, Kincer J, Matveev SV et al.: HIV protease inhibitors promote atherosclerotic lesion formation independent of dyslipidemia by increasing CD36-dependent cholesteryl ester accumulation in macrophages. J. Clin. Invest. 111, 389–397 (2003)
   Google Scholar
• Murata H, Hruz PW, Mueckler M: The mechanism of insulin resistance caused by HIV protease inhibitor therapy. J. Biol. Chem. 275, 20251–20254 (2000)
   Google Scholar
• dler-Wailes DC, Liu H, Ahmad F et al.: Effects of the human immunodeficiency virus-protease inhibitor, ritonavir, on basal and catecholamine-stimulated lipolysis. J. Clin. Endocrinol. Metab 90, 3251–3261 (2005)
   Google Scholar
• Hui DY: Effects of HIV protease inhibitor therapy on lipid metabolism. Prog. Lipid Res. 42, 81–92 (2003)
   Google Scholar
• Yan Q, Hruz PW: Direct Comparison of the acute in vivo effects of HIV protease inhibitors on peripheral glucose disposal. J. Acquir. Immune. Defic. Syndr. 40, 398–403 (2005)
   Google Scholar
• Koster JC, Remedi MS, Qiu H, Nichols CG, Hruz PW: HIV protease inhibitors acutely impair glucose-stimulated insulin release. Diabetes 52, 1695–1700 (2003)
   Google Scholar
• Schutt M, Zhou J, Meier M, Klein HH: Long-term effects of HIV-1 protease inhibitors on insulin secretion and insulin signaling in INS-1 beta cells. J. Endocrinol. 183, 445–454 (2004)
   Google Scholar
• Behrens G, Dejam A, Schmidt H et al.: Impaired glucose tolerance, beta cell function and lipid metabolism in HIV patients under treatment with protease inhibitors. AIDS 13, F63–F70 (1999)
   Google Scholar
• Dowell P, Flexner C, Kwiterovich PO, Lane MD: Suppression of preadipocyte differentiation and promotion of adipocyte death by HIV protease inhibitors. J. Biol. Chem. 275, 41325–41332 (2000)
   Google Scholar
• Grigem S, Fischer-Posovszky P, Debatin KM, Loizon E, Vidal H, Wabitsch M: The effect of the HIV protease inhibitor ritonavir on proliferation, differentiation, lipogenesis, gene expression and apoptosis of human preadipocytes and adipocytes. Horm. Metab. Res. 37, 602–609 (2005)
   Google Scholar
• Laurent N, de Bouard S, Guillamo JS et al.: Effects of the proteasome inhibitor ritonavir on glioma growth in vitro and in vivo. Mol. Cancer Ther. 3, 129–136 (2004)
   Google Scholar
• Vernochet C, Azoulay S, Duval D et al.: Human immunodeficiency virus protease inhibitors accumulate into cultured human adipocytes and alter expression of adipocytokines. J. Biol. Chem. 280, 2238–2243 (2005)
   Google Scholar
• Ishiki M, Klip A: Minireview: Recent developments in the regulation of glucose transporter-4 traffic: new signals, locations, and partners. Endocrinology 146, 5071–5078 (2005)
   Google Scholar
• Yan Q, Hruz PW: Direct comparison of the acute in vivo effects of HIV protease inhibitors on peripheral glucose disposal. J. Acquir. Immune. Defic. Syndr. 40, 398–403 (2005).
   Google Scholar
• First direct comparison of the in vivo potencies of HIV PIs on peripheral glucose disposal.
   Google Scholar
• Noor MA, Seneviratne T, Aweeka FT et al.: Indinavir acutely inhibits insulin-stimulated glucose disposal in humans: a randomized, placebo-controlled study. AIDS 16, F1–F8 (2002)
   Google Scholar
• Noor MA, Parker RA, O'Mara E et al.: The effects of HIV protease inhibitors atazanavir and lopinavir/ritonavir on insulin sensitivity in HIV-seronegative healthy adults. AIDS 18, 2137–2144 (2004)
   Google Scholar
• Lee GA, Rao MN, Grunfeld C: The effects of HIV protease inhibitors on carbohydrate and lipid metabolism. Curr. Infect. Dis. Rep. 6, 471–482 (2004)
   Google Scholar
• Lee GA, Seneviratne T, Noor MA et al.: The metabolic effects of lopinavir/ritonavir in HIV-negative men. AIDS 18, 641–649 (2004)
   Google Scholar
• Schwarz JM, Lee GA, Park S et al.: Indinavir increases glucose production in healthy HIV-negative men. AIDS 18, 1852–1854 (2004)
   Google Scholar
• den Boer MA, Berbee JF, Reiss P et al.: Ritonavir impairs lipoprotein lipasemediated lipolysis and decreases uptake of fatty acids in adipose tissue. Arterioscler. Thromb. Vasc. Biol. 26, 124–129 (2006).
   Google Scholar
• First demonstration that ritonavir decreases the uptake of very low-density lipoprotein–triglyceride (VLDL–TG)- derived fatty acid (FA) and albumin-bound FA in adipose tissue.
   Google Scholar
• Lee JN, Ye J: Proteolytic activation of sterol regulatory element-binding protein induced by cellular stress through depletion of insig-1. J. Biol. Chem. 279, 45257–45265 (2004)
   Google Scholar
• Horton JD, Goldstein JL, Brown MS: SREBPs: transcriptional mediators of lipid homeostasis. Cold Spring Harbour Symp. Quant. Biol. 67, 491–498 (2002)
   Google Scholar
• Rawson RB: The SREBP pathway – insights from Insigs and insects. Nature Rev. Mol. Cell Biol. 4, 631–640 (2003)
   Google Scholar
• Hirano Y, Yoshida M, Shimizu M, Sato R: Direct demonstration of rapid degradation of nuclear sterol regulatory element-binding proteins by the ubiquitin–proteasome pathway. J. Biol. Chem. 276, 36431–36437 (2001)
   Google Scholar
• Pajonk F, Himmelsbach J, Riess K, Sommer A, McBride WH: The human immunodeficiency virus (HIV)-1 protease inhibitor saquinavir inhibits proteasome function and causes apoptosis and radiosensitization in non-HIV-associated human cancer cells. Cancer Res. 62, 5230–5235 (2002)
   Google Scholar
• Schmidtke G, Holzhutter HG, Bogyo M et al.: How an inhibitor of the HIV-I protease modulates proteasome activity. J. Biol. Chem. 274, 35734–35740 (1999)
   Google Scholar
• Steinberg D, Carew TE, Fielding C et al.: Lipoproteins and the pathogenesis of atherosclerosis. Circulation 80, 719–723 (1989)
   Google Scholar
• Andre P, Groettrup M, Klenerman P et al.: An inhibitor of HIV-1 protease modulates proteasome activity, antigen presentation, and T cell responses. Proc. Natl Acad. Sci. USA 95, 13120–13124 (1998)
   Google Scholar
• Piccinini M, Rinaudo MT, Anselmino A et al.: The HIV protease inhibitors nelfinavir and saquinavir, but not a variety of HIV reverse transcriptase inhibitors, adversely affect human proteasome function. Antivir. Ther. 10, 215–223 (2005)
   Google Scholar
• Murata H, Hruz PW, Mueckler M: Indinavir inhibits the glucose transporter isoform GLUT4 at physiologic concentrations. AIDS 16, 859–863 (2002)
   Google Scholar
• Hruz PW, Murata H, Qiu H, Mueckler M: Indinavir induces acute and reversible peripheral insulin resistance in rats. Diabetes 51, 937–942 (2002)
   Google Scholar
• Mead JR, Irvine SA, Ramji DP: Lipoprotein lipase: structure, function, regulation, and role in disease. J. Mol. Med. 80, 753–769 (2002)
   Google Scholar
• Zhang B, MacNaul K, Szalkowski D, Li Z, Berger J, Moller DE: Inhibition of adipocyte differentiation by HIV protease inhibitors. J. Clin. Endocrinol. Metab. 84, 4274–4277 (1999).
   Google Scholar