Hyperlipidic Diet-induced Obesity Increased Proliferative Signals- AR, ERK1/2- on Mice Prostate, Which can be Restored through Physical Training

Main Article Content

João Vitor Pereira Leite
Daniela Cristina de Cario Calaça
Pedro Augusto Silva Nogueira
Renata Graciele Zanon
Daniele Lisboa Ribeiro

Abstract

Aims: To evaluate the effects of hyperlipidic diet on the mouse prostate and also investigate if physical exercise is able to restore such effects.

Methodology: Adult male Swiss mice were fed with a balanced (ND) or hyperlipidic diet (45% saturated fat, HD) for 16 weeks. Half were submitted to a sedentary (NDS and HDS) or exercise routine (swimming- NDE and HDE) for 8 weeks. Then, the prostate was analyzed by immunoreactions (proliferating cell nuclear antigen- PCNA, androgen receptor- AR, and estrogen receptor-ERβ), western blotting (ERK 1/2), and caspase-3 activity.

Results: We found that saturated fat uptake promoted 16% weight gain, increased fat-mass and hyperglycaemia, as well as reduced testosterone levels. In addition, HD atrophied prostate secretory epithelium and stimulated cell proliferation through higher expression of AR and activation of ERK signaling. Additionally, saturated fat reduced prostatic ERβ content. Physical exercise per se promoted an anabolic effect by increasing testosterone and stimulating cell proliferation in the prostate of sedentary animals. Finally, exercise was able to restore the proliferative signals caused by the hyperlipidic diet on prostate.

Conclusion: We suggest that the combination of hyperlipidic diet and sedentary lifestyle could negatively affected some prostate stimulating pathways that could trigger proliferative diseases in mice and physical exercise may be  an interesting strategy to reverse such effects.

Keywords:
Prostate, hyperlipidic diet, cell proliferation, androgen receptor, physical exercise.

Article Details

How to Cite
Leite, J. V. P., Calaça, D. C. de C., Nogueira, P. A. S., Zanon, R. G., & Ribeiro, D. L. (2020). Hyperlipidic Diet-induced Obesity Increased Proliferative Signals- AR, ERK1/2- on Mice Prostate, Which can be Restored through Physical Training. Advances in Research, 21(11), 79-90. https://doi.org/10.9734/air/2020/v21i1130272
Section
Original Research Article

References

World Health Organization. Obesity and overweight. Fact sheet, Last updated; 2017-09-27. Accessed: 4 December 2020. Available:http://apps.who.int/gho/data/view.main.BMI25AWBv?lang=en

Rawla P. Epidemiology of prostate cancer. World J Oncol. 2019;10(2):63-89.

Carvalheira JBC, Saad MJA. Insulin resistance/hyperinsulinemia associated diseases not included in the metabolic syndrome. Arq Bras Endocrinol Metabol. 2006;50(2):360-367.

Corona G, Vignozzi L, Rastrelli G, Lotti F, Cipriani S, Maggi M. Benign prostatic hyperplasia: A new metabolic disease of the aging male and its correlation with sexual dysfunctions. Int J Endocrinol. 2014;329456.

Vignozzi L, Maggi M. Prostate cancer: Intriguing data on inflammation and prostate cancer. Nat Rev Uro. 2014;11:369–370.

Pelser C, Mondul AM, Hollenbeck AR, Park Y. Dietary fat, fatty acids, and risk of prostate cancer in the NIH-AARP diet and health study. Cancer Epidemiol Biom Rev. 2013;22:697-707.

Zadra G, Photopoulos C, Loda M. The fat side of prostate cancer. Biochimica et Biophysica Acta. 2013;1831(10):1518-1532.

Liu YP, Hu F, Li D, Wang F, Zhu L, Chen W, Ge J, An R, Zhao Y. Does physical activity reduce the risk of prostate cancer? A systematic review and meta-analysis. Eur Urol. 2011;60:1029-1044.

Rundqvist H, Augsten M, Strömberg A, Rullman E, Mijwel S, Kharaziha P, Panaretakis T, Gustafsson T, Östman A. Effect of acute exercise on prostate cancer cell growth. PloS One. 2013;8(7):67579.

Nilsen TI, Romundstad PR, Vatten LJ. Recreational physical activity and risk of prostate cancer: A prospective population‐based study in Norway (the HUNT study). Int J Cancer. 2006;119(12):2943-2947.

Tir AMD, Labor M, Plavec D. The effects of physical activity on chronic subclinical systemic inflammation. Arh Hig Rada Toksikol. 2017;68(4):276-286.

Ribeiro DL, Pinto ME, Rafacho A, Bosqueiro JR, Maeda SY, Anselmo-Franci JA, Taboga SR, Góes RM. High-fat diet obesity associated with insulin resistance increases cell proliferation, estrogen receptor, and PI3K proteins in rat ventral prostate. J Androl. 2012;33(5):854-65.

Silva SA, Gobbo MG, Pinto-Fochi ME, Rafacho A, Taboga SR, Almeida EA, Góes RM, Ribeiro DL. Prostate hyperplasia caused by long-term obesity is characterized by high deposition of extracellular matrix and increased content of MMP- 9 and VEGF. Int J Exp Pathol. 2015;96(1):21-30.

Landim BC, de Jesus MM, Bosque BP, Zanon RG, da Silva CV, Góes RM, Ribeiro DL. Stimulating effect of palmitate and insulin on cell migration and proliferation in PNT1A and PC3 prostate cells: Counteracting role of metformin. Prostate. 2018;78(10):731-742.

Almeida PW, Gomes-Filho A, Ferreira AJ, Rodrigues CE, Dias-Peixoto MF, Russo RC, Teixeira MM, Cassali GD, Ferreira E, Santos IC, Garcia AM, Silami-Garcia E, Wisløff U, Pussieldi GA. Swim training sup¬presses tumor growth in mice. J Appl Physiol. 2009;107:261-265.

Riyahi F, Riyahi S. Effect of moderate swimming exercise on weight gain in high fat diet rats. Annals of Military and Health Sciences Research. 2016;14(1):46-50.

King AC, Tribble DL. The role of exercise in weight regulation in nonathletes. Sports Med. 1991;11(5):331-49.

Solomon TPJ, Haus JM, Kelly KR, Cook MD, Filion J, Rocco M, Kashyap SR, Watanabe RM, Arkoukis H, Kirwan JP. A low–glycemic index diet combined with exercise reduces insulin resistance, postprandial hyperinsulinemia, and glucose-dependent insulinotropic polypeptide responses in obese, prediabetic humans. Am J Clin Nutr. 2010;92(6):1359-1368.

Macdonald AA, Herbison GP, Showell M, Farquhar CM. The impact of body mass index on semen parameters and reproductive hormones in human males: A systematic review with meta-analysis. Hum Reprod Update. 2010;16(3):293-311.

Pinto-Fochi ME, Pytlowanciv EZ, Reame V, Rafacho A, Ribeiro DL, Taboga SR, Góes RM. A high-fat diet fed during different periods of life impairs steroidogenesis of rat Leydig cells. Reproduction. 2016;152(6):795-808.

Ehala-Aleksejev K, Punab M. The effect of metabolic syndrome on male reproductive health: A cross-sectional study in a group of fertile men and male partners of infertile couples. PLoS One. 2018;13:0194395.

França SCA, Barros Neto TL, Agresta MC, Lotufo RF, Kater CE. Divergent responses of serum testosterone and cortisol in athlete men after a marathon race. Arq Bras Endocrinol Metabol. 2006;50(6):1082-1087.

Hebert JR, Hurley TG, Olendzki BC, Teas J, Ma Y, Hampl JS. Nutritional and socioeconomic factors in relation to prostate cancer mortality: A cross-national study. J Nat Cancer Inst. 1998;90(21): 1637-1647.

Ribeiro DL, Caldeira EJ, Cândido EM, Manzato AJ, Taboga SR, Cagnon VH. Prostatic stromal microenvironment and experimental diabetes. Eur J Histochem. 2006;50(1):51-60.

Cakiroglu B, Hazar AI, Eyyupoglu SE, Can Balci MB, Sinanoglu O, Tuzlali P. The comparative evaluation of apoptosis produced by leuprolide or orchiectomy on rat prostate tissue. Arch Ital Urol Androl. 2016;87(4):265-269.

Feldman BJ, Feldman D. The development of androgen-independent prostate cancer. Nat Rev Cancer. 2001;1:34-45.

Cunha GR, Ricke W, Thomson A, Marker PC, Risbridger G, Hayward SW, Wang YZ, Donjacour AA, Kurita T. Hormonal, cellular and molecular regulation of normal and neoplastic prostatic development. J Steroid Biochem Mol Biol. 2004;92(4):221-36.

Denmeade SR, Lin XS, Isaacs JT. Role of programmed (apoptotic) cell death during the progression and therapy for prostate cancer. Prostate. 1996;28(4):251-265.

Sun Y, Liu WZ, Liu T, Feng X, Yang N, Zhou HF. Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J Recept Signal Transduct Res. 2015;35(6): 600-4.

Mistry T, Digby JE, Desai KM, Randeva HS. Obesity and prostate cancer: A role for adipokines. Eur Urol. 2007;52(1):46-53.

Fernandez-Twinn DS, Blackmore HL, Siggens L, Giussani DA, Cross CM, Foo R, Ozanne SE. The programming of cardiac hypertrophy in the offspring by maternal obesity is associated with hyper-insulinemia, AKT, ERK, and mTOR activation. Endocrinology. 2012;153(12): 5961-5971.

Wang M, Li S, Wang F, Zou J, Zhang Y. Aerobic exercise regulates blood lipid and insulin resistance via the toll like receptor 4 mediated extracellular signal regulated kinases/AMP activated protein kinases signaling pathway. Mol Med. 2018;17(6): 8339-8348.

Prins GS, Korach KS. The role of estrogens and estrogen receptors in normal prostate growth and disease. Steroids. 2008;73(3):233-44.