Lactate as an energy substrate and its role in carcinogenesis
DOI:
https://doi.org/10.33233/rbfe.v19i1.3988Keywords:
lactic acid; neoplasm; metabolismAbstract
Introduction: Lactate is the product of the degradation of pyruvate produced in the cytoplasm. For a long time, it was believed that it was produced only in the presence of hypoxia. Several studies have shown that lactate production depends on several factors and is not only influenced by the lactic anaerobic system. In addition, large concentrations of lactate are present in neoplastic cells, even at rest, a phenomenon known as the Warburg Effect, which can occur due to the high metabolic rate of tumor cells. Objective: This study aimed to discuss the physiological aspects involved in the production, metabolism and signaling of lactate, as well as to demonstrate the new therapeutic results related to the cancer clinic. Methods: This is a literature review study. Articles were selected in the languages: Portuguese, English and Spanish, published between 2000 and 2019, in the databases: MEDline via Pubmed, Scientific Electronic Library Online (Scielo). The gray literature was verified using Google Scholar and reference list of selected articles. Results: 43 articles related to lactate were included. The searches were carried out between July and December 2019. Conclusion: Lactate is a subtract produced in aerobic and anaerobic environments, in different exercise intensities. It can be used as an energy source during and after physical exercise, in addition to acting on anabolic signals. On the other hand, it can contribute to the maintenance of an environment that favors carcinogenic proliferation. This thinking has allowed the creation of new therapies to decrease tissue damage and eradicate malignant cells.
References
Benetti M, Santos RT, Carvalho T. Cinética de lactato em diferentes intensidades de exercícios e concentrações de oxigênio. Rev Bras Med Esporte 2000;6(2):50-6. https://doi.org/10.1590/S1517-86922000000200004
Bertuzzi RCM, Silva AEL, Abad CCC, Pires FO. Metabolismo do lactato: uma revisão sobre a bioenergética e a fadiga muscular. Rev Bras Cineantropom Desempenho Hum 2009;11(2):226-34. https://doi.org/10.5007/1980-0037.2009v11n2p226
Loenneke JP, Kim D, Fahs CA, Thiebaud RS, Abe T, Larson RD et al. The influence of exercise load with and without different levels of blood flow restriction on acute changes in muscle thickness and lactate. Clin Physiol Funct Imaging 2016;37(6):734-40. https://doi.org/10.1111/cpf.12367
Astorino TA, DeRevere JL, Anderson T, Kellogg E, Holstrom P, Ring S et al. Blood lactate concentration is not related to the increase in cardiorespiratory fitness induced by high intensity interval training. Int J Environ Res Public Health 2019;16(16):1-8. https://doi.org/10.3390/ijerph16162845
Filho RM, Machado TS. Transportadores de monocarboxilato (proteínas MCT): funções orgânicas durante a prática de exercícios aeróbicos e anaeróbicos. Efdeportes 2011;16(160). https://www.efdeportes.com/efd160/transportadores-de-monocarboxilato-proteinas-mct.htm
San-Millán I, Brooks GA. Reexamining cancer metabolism: Lactate production for carcinogenesis could be the purpose and explanation of the Warburg effect. Carcinogenesis 2017;38(2):119-33. https://doi.org/10.1093/carcin /bgw127
Furlan JP, Depieri ALV, Pedrosa MMD. Metabolismo do lactato e avaliação de desempenho: dois lados do mesmo processo. Rev Saúde e Pesquisa 2017;10(1):171-9. https://doi.org/10.177651/1983-1870.2017v10n1p171-179
Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th ed. New York: WH Freeman; 2002.
Pelarigo JG, Machado L, Fernandes RF, Greco CC, Vilas-Boas JP. Oxygen uptake kinetics and energy system‘s contribution around maximal lactate steady state swimming intensity. Plos One 2017;12(2):1-12. https://doi.org/10.1371/journal.pone.0167263
Junior NKM. Mecanismos fisiológicos da fadiga. Rev Bras Presc Fisiol Exerc 2015;9(56):671-720.
Voltarelli FA, Montrezol P, Santos F, Garcia A, Coelho CF, Fett CA. Cinética de lactato sanguíneo durante sessões contínuas de lutas simuladas de karatê: predominância aeróbia ou anaeróbia? Rev Bras Presc Fisiol Exerc 2009;3(18):566-571.
Westerblad H, Allen DG, Lännergren J. Muscle fatigue: Lactic acid or inorganic phosphate the major cause? News Physiol Sci 2002;17(1):17-21. https://doi.org/10.1152/physiologyonline.2002.17.1.17
Massidda M, Eynon N, Bachis V, Corrias L, Culigione C, Piras F, et al. Influence of the MCT1 rs1049434 on Indirect Muscle Disorders/Injuries in Elite Football Players. Sports Medic. 2015;1(1):1-6. https://doi.org/10.1186/s40798-015-0033-9
Santos GB. Lactato: de vilão a mocinho. Rev Bras Nutr Func 2019;42(77):23-30. https://doi.org/10.32809/2176-4522.42.77.04
Hall MM, Rajasekaran S, Thomsen TW, Peterson AR. Lactate: Friend or Foe. Advanced Sports Medicine Concepts and Controversies 2016;8(3S):S8-S15. https://doi.org/10.1016/j.pmrj.2015.10.018
Sobral MCC, Rocha AC. Resposta do lactato sanguíneo e da dor muscular de início tardio pós dois métodos distintos de treinamento de força. Rev Bras Presc Fisiol do Exerc 2017;11(66):284-92.
Schoenfeld BJ. Does exercise-induced muscle damage play a role in skeletal muscle hypertrophy? Cond Res 2012;26(5):1441-53. https://doi.org/10.1519/JSC.0b013e31824f207e
Oishi Y, Tsukamoto H, Yokowaka T, Hirotsu K, Shimazu M, Uchida K, et al. Mixed lactate and caffeine compound increases satellite cell activity and anabolic signals for muscle hypertrophy. J Appl Physiol 2015;118(6):742-9. https://doi.org/10.1152/japplphysiol.00054.2014
Guizoni DM, Lima ARR, Martinez PF, Damatto RL, Cezar MDM, Bonomo C, et al. Miostatina e redução da massa muscular em doenças crônicas. Rev Bras Clin Med 2010;8(3):266-71.
Bonen A. The expression of lactate transporters (MCT1 and MCT4) in heart and muscle. Eur J Appl Physiol 2001;86(1):6-11. https://doi.org/10.1007/s004210100516
Frollini AB, Dias R, Prestes J, Baganha RJ, Cereja DMP, Gomes LPR, et al. Exercício físico e regulação do lactato: Papel dos transportadores de monocarboxilato (Proteínas MCT). Rev Edu Físic 2008;19(3):453-63. https://doi.org/10.4025/reveducfis.v19i3.6007
Halestrap AP. Monocarboxylic acid transport. Compr Physiol 2013;3(4):1611-43. https://doi.org/10.1002/cphy.c130008
Petersen C, Nielsen MD, Andersen ES, Basse AL, Isidor MS, Markussen LK, et al. MCT1 and MCT4 expression and lactate flux activity increase during white and brown adipogenesis and impact adipocyte metabolism. Sci Rep 2017;7(1):1-29. https://doi.org/10.1038/s41598-017-13298-z
Bishop D, Edge J, Thomas C, Mercier J. High-intensity exercise acutely decreases the membrane content of MCT1 and MCT4 and buffer capacity in human skeletal muscle. J Appl Physiol 2007;102(2):616-21. https://doi.org/10.1152/japplphysiol.00590.2006
McGinley C, Bishop DJ. Influence of training intensity on adaptations in acid/base transport proteins, muscle buffer capacity, and repeated-sprint ability in active men. J Appl Physiol 2016;121(6):1290-305. https://doi.org/10.1152/japplphysiol.00630.2016
Cupeiro R, Pérez-Prieto R, Amigo T, Gortázar P, Redondo C, González-Lamuño D. Role of the monocarboxylate transporter MCT1 in the uptake of lactate during active recovery. Eur J Appl Physiol 2016;116(5):1005-10. https://doi.org/10.1007/s00421-016-3365-3
Neto AP, Junior AJS. Cinética da remoção do lactato sanguíneo durante exercício prolongado em 70% e 100% do limiar de lactato. Rev Bras Presc Fisiol do Exerc 2009;3(17):436-43.
Takimoto M, Hamada T. Acute exercise increases brain region-specific expression of MCT1, MCT2, MCT4, GLUT1, and COX IV proteins. J Appl Physiol. 2014;116(9):1238-50. https://doi.org/10.1152/japplphysiol.01288.2013
Cerosimo E. A importância do rim na manutenção da homeostase da glicose: aspectos teóricos e práticos do controle da glicemia em pacientes diabéticos portadores de insuficiência renal. J Bras Nefrol 2004;26(1):29-39.
Sabater D, Arriarán S, Romero M, Agnelli S, Remesar X, Fernández-López JA et al. Cultured 3T3L1 adipocytes dispose of excess medium glucose as lactate under abundant oxygen availability, Sci Rep 2015;4:3663. https://doi.org/10.1038/srep03663
Malheiros SVP. Integração metabólica nos períodos pós-prandial e jejum - um resumo. Rev Ensi Bioquí 2006;4(1):C1-C7. https://doi.org/10.16923/reb.v4i1.20
Murray B, Rosenbloom C. Fundamentals of glycogen metabolism for coaches and athletes. Nutri Rev 2018;76(4):243-259. https://doi.org/10.1093/nutrit/nuy001
Pérez-Escuredo J, Dadhich RK, Dhup S, Cacace A,Van Hée FV, Saedeleer CJ, et al. Lactate promotes glutamine uptake and metabolism in oxidative cancer cells. Cell Cycle. 2016;15(1):72-83. https://doi.org/10.1080/15384101.2015.1120930
Fouad YA, Aanei C. Revisiting the hallmarks of câncer. Am J Cancer Res 2017;7(5):1016-36.
Weyandt JD, Thompson CB, Giaccia AJ, Rathmell WK. Metabolic alterations in cancer and their potential as therapeutic targets. Am Soc Clin Oncol Educ Book 2017;37:825-32. https://doi.org/10.14694/EDBK_175561
Keenan MM, Chi JT. Alternative fuels for cancer cells. Cancer J 2015;21(2):49-55. https://doi.org/10.1097/PPO.0000000000000104
Ippolito L, Morandi A, Giannoni E, Chiarugi P. A metabolic driver in the tumour landscape. Trends Biochem Sci 2019;44(2):153-66. https://doi.org/10.1016/j.tibs.2018.10.011
Nenu I, Gafencu GA, Popescu T, Kacso G. A new frontier in the immunology and therapy of prostate cancer. J Cancer Res Ther 2017;13(3):406-11. https://doi.org/10.4103/0973-1482.163692.
Renner K, Singer K, Koehl GE, Geissler EK, Peter K, Siska PJ, et al. Metabolic hallmarks of tumor and immune cells in the tumor microenvironment. Front Immunol 2017;8:248. https://doi.org/10.3389/fimmu.2017.00248
Pérez-Escuredo J, Van Hée VF, Sboarina M, Falces J, Payen VL, Pellerin L, et al. Monocarboxylate transporters in the brain and in cancer. Biochim Biophys Acta 2016;1863(10):2481-97. https://doi.org/10.1016/j.bbamcr.2016.03.013
Pucino V, Cucchi D,Mauro C. Lactate transporters as therapeutic targets in cancer and inflammatory disease. Expert Opin Ther Targets 2018;22(9):735-43. https://doi.org/10.1080/14728222.2018.1511706
Amorim MO, Vieira MM, Gonçalves IV, Rhana P, Rodrigues ALP. Câncer de mama: Reprogramação do metabolismo tumoral. Rev Med Minas Gerais 2018;28 e-1937:1-9. https://doi.org/10.5935/2238-3182.20180078
Guan X, Bryniarski MA, Morris ME. In vitro and in vivo efficacy of the monocarboxylate transporter 1 inhibitor AR-C155858 in the Murine 4T1 breast cancer tumor model. AAPS J 2018;21(1):3. https://doi.org/10.1208/s12248-018-0261-2
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