**9. References**

418 Dyslipidemia - From Prevention to Treatment

the changing dietary habits and rising incidences of BPH, it becomes increasingly important to delineate the precise roles of lipids in the normal as well as pathological growth of the prostate. Although, experimental and clinical/epidemiological studies suggest that these conditions contribute to the pathogenesis of both insulin-resistance and BPH, the direct role of lipids in the pathogenesis of prostatic enlargement is far from complete understanding. Role of lipids in the progression of insulin-resistance and other disorders and indirect effect on the prostatic growth owing to compensatory rise in the plasma insulin level is essentially correct, but what has emerged is that the lipids might have a direct influence on the normal

Fig. 2. Modern lifestyle associated changes including increased consumption of fat-rich diets and decreased physical activities contributes to the development of lipid-disorders and obesity. The present illustration demonstrates the possible influence of these factors on the prostatic growth and development. IR; insulin receptor, IGF-IR; insulin-like growth factor-1 receptor, PPAR-α/γ; peroxisome-proliferator activated receptor alpha/gamma, ATX;

In addition to the genetic factors, environmental factors such as physical inactivity and excessive intake of dietary fat contribute to the increased incidence of lipid-disorders and obesity worldwide. These factors directly as well as indirectly promote the prostatic growth

as well as pathological growth of the prostate.

autotaxin, LPA, lysophosphatidic acid.

**7. Conclusion**


Lipids in the Pathogenesis of Benign Prostatic Hyperplasia: Emerging Connections 421

Hammarsten, J., Hogstedt, B., 1999. Clinical, anthropometric, metabolic and insulin profile

Hammarsten, J., Hogstedt, B., 2001. Hyperinsulinaemia as a risk factor for developing

Hammarsten, J., Hogstedt, B., Holthuis, N., Mellstrom, D., 1998. Components of the

Homma, Y., Kondo, Y., Kaneko, M., Kitamura, T., Nyou, W.T., Yanagisawa, M., Yamamoto,

Hoon Kim, J., Lee, S.Y., Myung, S.C., Kim, Y.S., Kim, T.H., Kim, M.K., 2008. Clinical

Ikeda, K., Wada, Y., Foster, H.E., Jr., Wang, Z., Weiss, R.M., Latifpour, J., 2000. Experimental

Jiang, M., Fernandez, S., Jerome, W.G., He, Y., Yu, X., Cai, H., Boone, B., Yi, Y., Magnuson,

Kaplan-Lefko, P.J., Sutherland, B.W., Evangelou, A.I., Hadsell, D.L., Barrios, R.J., Foster,

Kasturi, S., Russell, S., McVary, K.T., 2006. Metabolic syndrome and lower urinary tract symptoms secondary to benign prostatic hyperplasia. *Curr Urol Rep*, 7, 288-292. Kim, B.H., Kim, C.I., Chang, H.S., Choe, M.S., Jung, H.R., Kim, D.Y., Park, C.H., 2011a.

Kim, G.W., Doo, S.W., Yang, W.J., Song, Y.S., 2010. Effects of obesity on prostate volume and lower urinary tract symptoms in korean men. *Korean J Urol*, 51, 344-347. Kim, J.M., Song, P.H., Kim, H.T., Moon, K.H., 2011b. Effect of obesity on prostate-specific

Kogai, M.A., Lutov, U.V., Selyatitskaya, V.G., 2008. Hormonal and biochemical parameters

Kosaki, A., Pillay, T.S., Xu, L., Webster, N.J., 1995. The B isoform of the insulin receptor signals more efficiently than the A isoform in HepG2 cells. *J Biol Chem*, 270, 20816-20823. Kristal, A.R., Arnold, K.B., Schenk, J.M., Neuhouser, M.L., Goodman, P., Penson, D.F.,

expression of transforming growth factor-beta. *J Urol*, 164, 180-185. Ingraham, H.A., 2011. Metabolism: A lipid for fat disorders. *Nature*, 474, 455-456. Irvine, R.F., 2003. Nuclear lipid signalling. *Nat Rev Mol Cell Biol*, 4, 349-360.

benign prostatic hyperplasia. *Eur Urol*, 39, 151-158.

hyperplasia. *Prostate cancer and prostatic dis*, 1, 157-162.

cholesterol in rat prostate. *Carcinogenesis*, 25, 1011-1014.

involving active autophagy. *Cell Death Differ*, 17, 469-481.

spontaneous metastogenesis. *Oncogene*, 27, 2868-2876.

with benign prostatic hyperplasia. *Korean J Urol*, 52, 401-405.

29-36.

*Androl*, 10, 923-928.

*Korean J Urol*, 52, 253-259.

*Exp Biol Med*, 146, 806-808.

prevention trial. *Am J Epidemiol*, 167, 925-934.

of men with fast annual growth rates of benign prostatic hyperplasia. *Blood Press*, 8,

metabolic syndrome-risk factors for the development of benign prostatic

Y., Kakizoe, T., 2004. Promotion of carcinogenesis and oxidative stress by dietary

significance of the leptin and leptin receptor expressions in prostate tissues. *Asian J* 

diabetes-induced regression of the rat prostate is associated with an increased

M.A., Roy-Burman, P., Matusik, R.J., Shappell, S.B., Hayward, S.W., Disruption of PPARgamma signaling results in mouse prostatic intraepithelial neoplasia

B.A., Demayo, F., Greenberg, N.M., 2008. Enforced epithelial expression of IGF-1 causes hyperplastic prostate growth while negative selection is requisite for

Cyclooxygenase-2 overexpression in chronic inflammation associated with benign prostatic hyperplasia: is it related to apoptosis and angiogenesis of prostate cancer?

antigen, prostate volume, and international prostate symptom score in patients

of metabolic syndrome in male patients with body weight excess and obesity. *Bull* 

Thompson, I.M., 2008. Dietary patterns, supplement use, and the risk of symptomatic benign prostatic hyperplasia: results from the prostate cancer


Chokkalingam, A.P., Gao, Y.T., Deng, J., Stanczyk, F.Z., Sesterhenn, I.A., Mostofi, F.K.,

Chughtai, B., Lee, R., Te, A., Kaplan, S., Inflammation and benign prostatic hyperplasia:

Cox, M.E., Gleave, M.E., Zakikhani, M., Bell, R.H., Piura, E., Vickers, E., Cunningham, M.,

Culig, Z., Hobisch, A., Cronauer, M.V., Radmayr, C., Hittmair, A., Zhang, J., Thurnher, M.,

Dahle, S.E., Chokkalingam, A.P., Gao, Y.T., Deng, J., Stanczyk, F.Z., Hsing, A.W., 2002. Body

Donnell, R.F., 2011. Benign prostate hyperplasia: a review of the year's progress from bench

Escobar, E.L., Gomes-Marcondes, M.C., Carvalho, H.F., 2009. Dietary fatty acid quality affects AR and PPARgamma levels and prostate growth. *Prostate*, 69, 548-558. Ferry, G., Moulharat, N., Pradere, J.P., Desos, P., Try, A., Genton, A., Giganti, A., Beucher-

Ferry, G., Tellier, E., Try, A., Gres, S., Naime, I., Simon, M.F., Rodriguez, M., Boucher, J.,

Francisco, C., Francois, D., 2010. New concepts and pathophysiology of lower urinary tract

Frasca, F., Pandini, G., Scalia, P., Sciacca, L., Mineo, R., Costantino, A., Goldfine, I.D.,

Ghosh, J., Myers, C.E., 1997. Arachidonic acid stimulates prostate cancer cell growth: critical

Giovannucci, E., Rimm, E.B., Chute, C.G., Kawachi, I., Colditz, G.A., Stampfer, M.J., Willett,

Giudice, J., Leskow, F.C., Arndt-Jovin, D.J., Jovin, T.M., Jares-Erijman, E.A., 2011.

Hammarsten, J., Damber, J.E., Karlsson, M., Knutson, T., Ljunggren, O., Ohlsson, C., Peeker,

role of 5-lipoxygenase. *Biochem Biophy Res Commun*, 235, 418-423.

Belfiore, A., Vigneri, R., 1999. Insulin receptor isoform A, a newly recognized, highaffinity insulin-like growth factor II receptor in fetal and cancer cells. *Mol Cell Biol*,

W.C., 1994. Obesity and benign prostatic hyperplasia. *Am J Epidemiol*, 140, 989-1002.

Differential endocytosis and signaling dynamics of insulin receptor variants IR-A

R., Smith, U., Mellstrom, D., 2009. Insulin and free oestradiol are independent risk factors for benign prostatic hyperplasia. *Prostate Cancer Prostatic Dis*, 12, 160-165.

prostatic hyperplasia. *Prostate*, 52, 98-105.

prostate cancers. *Prostate*, 69, 33-40.

hyperplasia. *J Urol*, 168, 599-604.

to clinic. *Curr Opin Urol*, 21, 22-26.

819.

18162-18169.

19, 3278-3288.

clinical implications. *Curr Urol Rep*, 12, 274-277.

peptide growth factors. *Prostate*, 28, 392-405.

symptoms in men. *Eur Urol Suppl*, 9, 472-476.

and IR-B. *J Cell Sci*, 124, 801-811.

Fraumeni, J.F., Jr., Hsing, A.W., 2002. Insulin-like growth factors and risk of benign

Larsson, O., Fazli, L., Pollak, M., 2009. Insulin receptor expression by human

Bartsch, G., Klocker, H., 1996. Regulation of prostatic growth and function by

size and serum levels of insulin and leptin in relation to the risk of benign prostatic

Gaudin, M., Lonchampt, M., Bertrand, M., Saulnier-Blache, J.S., Tucker, G.C., Cordi, A., Boutin, J.A., 2008. S32826, a nanomolar inhibitor of autotaxin: discovery, synthesis and applications as a pharmacological tool. *J Pharmacol Exp Ther*, 327, 809-

Tack, I., Gesta, S., Chomarat, P., Dieu, M., Raes, M., Galizzi, J.P., Valet, P., Boutin, J.A., Saulnier-Blache, J.S., 2003. Autotaxin is released from adipocytes, catalyzes lysophosphatidic acid synthesis, and activates preadipocyte proliferation. Upregulated expression with adipocyte differentiation and obesity. *J Biol Chem*, 278,


Lipids in the Pathogenesis of Benign Prostatic Hyperplasia: Emerging Connections 423

Nandeesha, H., Koner, B.C., Dorairajan, L.N., Sen, S.K., 2006. Hyperinsulinemia and

Nicholson, T.M., Ricke, W.A., 2011. Androgens and estrogens in benign prostatic

North, E.J., Howard, A.L., Wanjala, I.W., Pham, T.C., Baker, D.L., Parrill, A.L., 2010.

North, E.J., Osborne, D.A., Bridson, P.K., Baker, D.L., Parrill, A.L., 2009. Autotaxin structure-

Pandalai, P.K., Pilat, M.J., Yamazaki, K., Naik, H., Pienta, K.J., 1996. The effects of omega-3

Pandini, G., Frasca, F., Mineo, R., Sciacca, L., Vigneri, R., Belfiore, A., 2002. Insulin/insulin-

Parrill, A.L., Baker, D.L., 2010. Autotaxin inhibitors: a perspective on initial medicinal

Parsons, J.K., 2011. Lifestyle factors, benign prostatic hyperplasia, and lower urinary tract

Parsons, J.K., Bergstrom, J., Barrett-Connor, E., 2008. Lipids, lipoproteins and the risk of benign prostatic hyperplasia in community-dwelling men. *BJU Int*, 101, 313-318. Parsons, J.K., Carter, H.B., Partin, A.W., Windham, B.G., Metter, E.J., Ferrucci, L., Landis, P.,

Parsons, J.K., Kashefi, C., 2008. Physical activity, benign prostatic hyperplasia, and lower

Parsons, J.K., Sarma, A.V., McVary, K., Wei, J.T., 2009. Obesity and benign prostatic

Rahman, N.U., Phonsombat, S., Bochinski, D., Carrion, R.E., Nunes, L., Lue, T.F., 2007. An

Rancoule, C., Pradere, J.P., Gonzalez, J., Klein, J., Valet, P., Bascands, J.L., Schanstra, J.P.,

Rick, F.G., Schally, A.V., Block, N.L., Nadji, M., Szepeshazi, K., Zarandi, M., Vidaurre, I.,

Rose, D.P., Connolly, J.M., 1991. Effects of fatty acids and eicosanoid synthesis inhibitors on the growth of two human prostate cancer cell lines. *Prostate*, 18, 243-254.

hyperplasia: Past, present and future. *Differentiation*, (In-press).

small-molecule autotaxin inhibitors. *J Med Chem*, 53, 3095-3105.

93.

820.

*Med Chem*, 17, 3433-3442.

differentiation. *PLoS One*, 4, e8055.

symptoms. *Curr Opin Urol*, 21, 1-4.

*Clin Endocrinol Metab*, 91, 2562-2568.

directions. *J Urol*, 182, S27-31.

urinary tract symptoms. *Eur Urol,* 53, 1228-1235.

hyperlipidaemic rat. *BJU Int*, 100, 658-663.

fibrosis. *Expert Opin Investig Drugs*, 20, 657-667.

hyperplasia. *Proc Natl Acad Sci U S A*, 108, 3755-3760.

chemistry efforts. *Expert Opin Ther Pat*, 20, 1619-1625.

dyslipidemia in non-diabetic benign prostatic hyperplasia. *Clin Chim Acta*, 370, 89-

Pharmacophore development and application toward the identification of novel,

activity relationships revealed through lysophosphatidylcholine analogs. *Bioorg* 

and omega-6 fatty acids on in vitro prostate cancer growth. *Anticancer Res*, 16, 815-

like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved. *J Biol Chem*, 277, 39684-39695. Parast, M.M., Yu, H., Ciric, A., Salata, M.W., Davis, V., Milstone, D.S., 2009. PPARgamma

regulates trophoblast proliferation and promotes labyrinthine trilineage

Platz, E.A., 2006. Metabolic factors associated with benign prostatic hyperplasia. *J* 

hyperplasia: clinical connections, emerging etiological paradigms and future

animal model to study lower urinary tract symptoms and erectile dysfunction: the

Saulnier-Blache, J.S., 2011. Lysophosphatidic acid-1-receptor targeting agents for

Perez, R., Halmos, G., Szalontay, L., 2011. Antagonists of growth hormonereleasing hormone (GHRH) reduce prostate size in experimental benign prostatic


Kulkarni, P., Getzenberg, R.H., 2009. High-fat diet, obesity and prostate disease: the ATX-

Lagiou, P., Signorello, L.B., Trichopoulos, D., Tzonou, A., Trichopoulou, A., Mantzoros, C.S.,

Langlois, W.J., Sasaoka, T., Yip, C.C., Olefsky, J.M., 1995. Functional characterization of

Lee, S.H., Kim, J.C., Lee, J.Y., Kim, J.H., Oh, C.Y., Lee, S.W., Yoo, S.J., Chung, B.H., 2009.

Leibiger, B., Leibiger, I.B., Moede, T., Kemper, S., Kulkarni, R.N., Kahn, C.R., de Vargas,

Li, G., Barrett, E.J., Wang, H., Chai, W., Liu, Z., 2005. Insulin at physiological concentrations

Marker, P.C., Donjacour, A.A., Dahiya, R., Cunha, G.R., 2003. Hormonal, cellular, and

Maserejian, N.N., Giovannucci, E.L., McKinlay, J.B., 2009. Dietary macronutrients,

McKeehan, W.L., Adams, P.S., Rosser, M.P., 1984. Direct mitogenic effects of insulin,

Morales-Garcia, J.A., Luna-Medina, R., Alfaro-Cervello, C., Cortes-Canteli, M., Santos, A.,

Morrione, A., Valentinis, B., Xu, S.Q., Yumet, G., Louvi, A., Efstratiadis, A., Baserga, R., 1997.

Moyad, M.A., Lowe, F.C., 2008. Educating patients about lifestyle modifications for prostate

Nam, S.Y., Lee, E.J., Kim, K.R., Cha, B.S., Song, Y.D., Lim, S.K., Lee, H.C., Huh, K.B., 1997.

molecular control of prostatic development. *Dev Biol*, 253, 165-174.

serum-free, primary cell culture. *Cancer Res*, 44, 1998-2010.

in vitro and in vivo. *Glia*, 59, 293-307.

health. *Am J Med*, 121, S34-42.

receptor. *Proc Natl Acad Sci U S A*, 94, 3777-3782.

hormone. *Int J Obes Relat Metab Disord*, 21, 355-359.

like growth factor 1 or insulin receptors. *Endocrinology*, 136, 1978-1986. Lee, J.M., Lee, Y.K., Mamrosh, J.L., Busby, S.A., Griffin, P.R., Pathak, M.C., Ortlund, E.A.,

1998. Leptin in relation to prostate cancer and benign prostatic hyperplasia. *Int J* 

hybrid receptors composed of a truncated insulin receptor and wild type insulin-

Moore, D.D., 2011. A nuclear-receptor-dependent phosphatidylcholine pathway

Effects of obesity on lower urinary tract symptoms in Korean BPH patients. *Asian J* 

L.M., Berggren, P.O., 2001. Selective insulin signaling through A and B insulin receptors regulates transcription of insulin and glucokinase genes in pancreatic

selectively activates insulin but not insulin-like growth factor I (IGF-I) or insulin/IGF-I hybrid receptors in endothelial cells. *Endocrinology*, 146, 4690-4696. Liu, Y., Zuckier, L.S., Ghesani, N.V., 2010. Dominant uptake of fatty acid over glucose by

prostate cells: a potential new diagnostic and therapeutic approach. *Anticancer Res*,

cholesterol, and sodium and lower urinary tract symptoms in men. *Eur Urol*, 55,

epidermal growth factor, glucocorticoid, cholera toxin, unknown pituitary factors and possibly prolactin, but not androgen, on normal rat prostate epithelial cells in

Garcia-Verdugo, J.M., Perez-Castillo, A., 2011. Peroxisome proliferator-activated receptor gamma ligands regulate neural stem cell proliferation and differentiation

Insulin-like growth factor II stimulates cell proliferation through the insulin

Effect of obesity on total and free insulin-like growth factor (IGF)-1, and their relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth

LPA axis? *Nat Clin Pract Urol*, 6, 128-131.

with antidiabetic effects. *Nature*, 474, 506-510.

*Cancer*, 76, 25-28.

*Androl*. 11, 663-668.

30, 369-374.

1179-1189.

beta cells. *Mol Cell*, 7, 559-570.


Lipids in the Pathogenesis of Benign Prostatic Hyperplasia: Emerging Connections 425

Suzuki, S., Platz, E.A., Kawachi, I., Willett, W.C., Giovannucci, E., 2002. Intakes of energy

Uhles, S., Moede, T., Leibiger, B., Berggren, P.O., Leibiger, I.B., 2003. Isoform-specific insulin

Van Meeteren, L.A., Moolenaar, W.H., 2007. Regulation and biological activities of the

Vikram, A., Jena, G., 2010. S961, an insulin receptor antagonist causes hyperinsulinemia,

Vikram, A., Jena, G., 2011a. Diet-induced hyperinsulinemia accelerates growth of human

Vikram, A., Jena, G., 2011b. Role of insulin and testosterone in prostatic growth: who is

Vikram, A., Jena, G., Ramarao, P., 2010a. Insulin-resistance and benign prostatic

Vikram, A., Jena, G., Ramarao, P., 2010b. Pioglitazone attenuates prostatic enlargement in

Vikram, A., Jena, G., Ramarao, P., 2011a. Insulin-resistance reduces botulinum neurotoxin-

Vikram, A., Jena, G.B., Ramarao, P., 2010c. Increased cell proliferation and contractility of

Vikram, A., Kushwaha, S., Jena, G.B., 2011b. Relative influence of testosterone and insulin in the regulation of prostatic cell proliferation and growth. *Steroids*, 76, 416-423. Vikram, A., Tripathi, D.N., Ramarao, P., Jena, G.B., 2008. Intervention of D-glucose

Vogeser, M., Schwandt, P., Haas, G.M., Broedl, U.C., Lehrke, M., Parhofer, K.G., 2009. BMI

Vogt, B., Carrascosa, J.M., Ermel, B., Ullrich, A., Haring, H.U., 1991. The two isotypes of the

Vykhovanets, E.V., Shankar, E., Vykhovanets, O.V., Shukla, S., Gupta, S., 2011. High-fat diet

Wang, L., Yang, J.R., Yang, L.Y., Liu, Z.T., 2008. Chronic inflammation in benign prostatic hyperplasia: implications for therapy. *Med Hypotheses*, 70, 1021-1023. Wang, X., Kruithof-de Julio, M., Economides, K.D., Walker, D., Yu, H., Halili, M.V., Hu, Y.P.,

Wang, Z., Olumi, A.F., 2011. Diabetes, growth hormone-insulin-like growth factor pathways and association to benign prostatic hyperplasia. *Differentiation*, (In-Press).

and hyperinsulinemia in children. *Clin Biochem*, 42, 1427-1430.

kinetics. *Biochem Biophy Res Commun*, 177, 1013-1018.

cell of origin for prostate cancer. *Nature*, 461, 495-500.

diet-induced insulin-resistant rats by altering lipid distribution and

type A induced prostatic atrophy and apoptosis in rats. *Eur J Pharmacol*, 650, 356-

prostate in insulin resistant rats: linking hyperinsulinemia with benign prostate

ameliorates the toxicity of streptozotocin in accessory sex organs of rat. *Toxicol Appl* 

human insulin receptor (HIR-A and HIR-B) follow different internalization

increases NF-kappaB signaling in the prostate of reporter mice. *Prostate*, 71, 147-

Price, S.M., Abate-Shen, C., Shen, M.M., 2009. A luminal epithelial stem cell that is a

autotaxin-LPA axis. *Prog Lipid Res*, 46, 145-160.

doing what? *Med Hypotheses*, 76, 474-478.

hyperplasia. *Prostate*, 70, 79-89.

*Pharmacol*, 226, 84-93.

androgen independent PC-3 cells. *Nut Cancer,* (In-Press).

hyperplasia: the connection. *Eur J Pharmacol*, 641, 75-81.

hyperinsulinaemia. *Brit J Pharmacol*, 161, 1708-1721.

689-697.

1327-1337.

363.

156.

*Commun*, 398, 260-265.

and macronutrients and the risk of benign prostatic hyperplasia. *Am J Clin Nutr*, 75,

receptor signaling involves different plasma membrane domains. *J Cell Biol*, 163,

insulin-resistance and depletion of energy stores in rats. *Biochem Biophy Res* 


Saigal, C.S., Joyce, G., 2005. Economic costs of benign prostatic hyperplasia in the private

Sakamoto, S., Yokoyama, M., Zhang, X., Prakash, K., Nagao, K., Hatanaka, T., Getzenberg,

Sanda, M.G., Beaty, T.H., Stutzman, R.E., Childs, B., Walsh, P.C., 1994. Genetic susceptibility

Schenk, J.M., Kristal, A.R., Neuhouser, M.L., Tangen, C.M., White, E., Lin, D.W., Kratz, M.,

Schenk, J.M., Kristal, A.R., Neuhouser, M.L., Tangen, C.M., White, E., Lin, D.W., Thompson,

Sciacca, L., Prisco, M., Wu, A., Belfiore, A., Vigneri, R., Baserga, R., 2003. Signaling

Simopoulos, A.P., 1999. Essential fatty acids in health and chronic disease. *Am J Clin Nutr*,

Smith, C.D., Wells, W.W., 1983a. Phosphorylation of rat liver nuclear envelopes. I. Characterization of in vitro protein phosphorylation. *J Biol Chem*, 258, 9360-9367. Smith, C.D., Wells, W.W., 1983b. Phosphorylation of rat liver nuclear envelopes. II. Characterization of in vitro lipid phosphorylation. *J Biol Chem*, 258, 9368-9373. Soos, M.A., Whittaker, J., Lammers, R., Ullrich, A., Siddle, K., 1990. Receptors for insulin and

Srinivasan, G., Campbell, E., Bashirelahi, N., 1995. Androgen, estrogen, and progesterone receptors in normal and aging prostates. *Microsc Res Tech*, 30, 293-304. Story, M.T., 1995. Regulation of prostate growth by fibroblast growth factors. *World J Urol*,

Stranne, J., Damber, J.E., Fall, M., Hammarsten, J., Knutson, T., Peeker, R., 2009. One-third of

Subbaramaiah, K., Howe, L.R., Bhardwaj, P., Du, B., Gravaghi, C., Yantiss, R.K., Zhou, X.K.,

Suthagar, E., Soudamani, S., Yuvaraj, S., Ismail Khan, A., Aruldhas, M.M., Balasubramanian,

presence or absence of IR substrate-1. *Endocrinology*, 144, 2650-2658. Sekine, Y., Osei-Hwedieh, D., Matsuda, K., Raghavachari, N., Liu, D., Furuya, Y., Koike, H.,

lysophosphatidic acid. *Endocrinology*, 145, 2929-2940.

of benign prostatic hyperplasia. *J Urol*, 152, 115-119.

peroxidase 3 in mouse prostate. *Prostate,* (In-Press).

receptors in transfected cells. *Biochem J*, 270, 383-390.

symptoms. *Scandinavian J Urol Nephrol*, 43, 199-205.

mouse mammary gland. *Cancer Prev Res (Phila)*, 4, 329-346.

on rat ventral prostate. *Biomed Pharmacother*, 63, 43-50.

prevention trial. *Am J Epidemiol*, 171, 571-582.

R.H., Kakehi, Y., 2004. Increased expression of CYR61, an extracellular matrix signaling protein, in human benign prostatic hyperplasia and its regulation by

Thompson, I.M., 2010. Biomarkers of systemic inflammation and risk of incident, symptomatic benign prostatic hyperplasia: results from the prostate cancer

I.M., 2009. Serum adiponectin, C-peptide and leptin and risk of symptomatic benign prostatic hyperplasia: results from the Prostate Cancer Prevention Trial.

differences from the A and B isoforms of the insulin receptor (IR) in 32D cells in the

Suzuki, K., Remaley, A.T., 2011. High fat diet reduces the expression of glutathione

insulin-like growth factor-I can form hybrid dimers. Characterisation of hybrid

the Swedish male population over 50 years of age suffers from lower urinary tract

Blaho, V.A., Hla, T., Yang, P., Kopelovich, L., Hudis, C.A., Dannenberg, A.J., 2011. Obesity is associated with inflammation and elevated aromatase expression in the

K., 2009. Effects of streptozotocin (STZ)-induced diabetes and insulin replacement

sector. *J Urol*, 173, 1309-1313.

*Prostate*, 69, 1303-1311.

70, 560S-569S.

13, 297-305.


**21** 

*Brasil* 

**Dyslipidemia in Patients with Lipodystrophy** 

Dyslipidemia is a change in serum lipids levels, which is associated with increased risk of cardiovascular events when are found elevated (American Heart Association, 2002, Sposito et al., 2007). Before introduction of antiretroviral therapy (HAART), patients with acquired immunodeficiency syndrome (AIDS) developed a dyslipidemia characterized by isolated elevation of triglycerides (TG) and decrease in total cholesterol (TC) and its fractions (Gkrania-Klotsas & Klotsas, 2007; Mulligan, 2003). With the advent of HAART, especially with the use of protease inhibitors (PI), this situation changed to a lipid profile with elevated TG, TC, lipoproteins of very low and low density (VLDL-C and LDL-C) and decrease in high density lipoprotein (HDL-C), leaving these patients at risk for developing diabetes, hypertension and other complications (Chen et al., 2002; Furtado et al., 2007; Garg, 2000; Gkrania-Klotsas & Klotsas, 2007; Kotler, 2008; Mulligan, 2003; Sattler, 2008; Segarra-

Studies estimate that the prevalence of dyslipidemia in patients with HIV (Human Immunodeficiency Virus) during use of antiretroviral therapy can vary from 33% to 82% and may be influenced by several factors including study type, sample type and time of

According to UNAIDS and World Health Organization (WHO) (2009) there was a large increase in the prevalence of HIV carriers in the world, reaching 33.4 million in 2008, value explained by the maintenance of annual incidence and the increase of the survival (Lihn et al. 2003; Mallewa et al., 2008). However, was noted a illness pattern change of these patients which ever left to be affected by a clinical feature characteristic of opportunistic diseases to develop HIV lipodystrophy syndrome (HIVLS) (Kramer et al., 2009; Ministry of Health of

Body composition abnormalities have been reported in 40-50% of HIV-positive outpatients. This proportion is higher in patients receiving antiretroviral therapy. The rate of lipodystrophy can be high depending on the characteristics of the cohort (sex, age and possibly race), the type and duration of antiretroviral therapy (Grinspoon & Carr, 2005).

HAART (Gkrania-Klotsas & Klotsas, 2007; Schering & Tovar, 2006; Yu et al., 2005).

Newnham, 2002; Schering & Tovar, 2006; Yu et al., 2005).

Brazil, 2008; Samaras et al., 2009; Stankov & Behrens, 2010).

**2. HIV lipodystrophy syndrome** 

**1. Introduction** 

**in the Use of Antiretroviral Therapy** 

Rosana Libonati, Cláudia Dutra, Leonardo Barbosa, Sandro Oliveira, Paulo Lisbôa and Marcus Libonati *Tropical Medicine Center, Federal University of the Pará, Pará* 

