Micro-ARN, resistencia a la insulina y ejercicio físico: Avances científicos en el control del Síndrome Metabólico
Resumen
Los micro-ARN (miARN) se han descrito como moléculas no codificantes asociadas con la regulación génica postranscripcional y, por lo tanto, capaces de regular el crecimiento, la diferenciación y los procesos metabólicos. Aunque sus mecanismos aún no se conocen por completo, su función principal es la degradación del ARNm maduro o la inhibición de la traducción. Recientemente, el micro-ARN miR-335 fue validado para regular a la baja el sistema antioxidante enzimático, favoreciendo consecuentemente la aparición de estrés oxidativo, mientras que el micro-ARN miR-23 fue validado para inhibir la expresión de PGC1α y, en consecuencia, reducir la función mitocondrial. La resistencia a la insulina en el músculo esquelético es una característica de los diabéticos. Aunque su mecanismo aún no se comprende completamente, existe una correlación entre la resistencia a la insulina y el contenido de lípidos intracelulares. Existe mucha evidencia de que este mecanismo se acompaña de una baja actividad mitocondrial y un aumento en la producción de especies reactivas de oxígeno (ROS), lo que sugiere que los miRNA pueden expresarse en tejido muscular con resistencia a la insulina.
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-Ambros, V. The functions of animal microRNAs. Nature. Vol. 16. p. 350-355. 2004.Anderson, E. J.; e colaboradores. Mitochondrial H2O2emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. Journal of Clinical Investigation. Vol. 119. p. 573-581. 2009.
-Barbosa, R. B.; e colaboradores. Campanha nacional de detecção de casos de diabetes mellitos no Brasil: relatório preliminar. Pan American Journal of Public Health. Vol. 10. p. 324-327. 2001.
-Bartel, D. P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. Vol. 116. p. 281-297. 2004.
-Boden, G.; e colaboradores. Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-κB pathway in rat liver.Diabetes. Vol. 54. p. 3458-3465. 2005.
-Brehm, A.; e colaboradores. Increased lipid availability impairs insulin-stimulated ATP synthesis in human skeletal muscle. Diabetes. Vol. 55. p. 136-140. 2006.
-Butler, A. E.; e colaboradores. β-Cell Deficit and Increased β-Cell Apoptosis in Humans With Type 2 Diabetes. Diabetes. Vol. 52. p. 102-110. 2003.
-Cardinali, B.; e colaboradores.Microrna-221 and Microrna-222 Modulate Differentiation and Maturation of Skeletal Muscle Cells.PLoS ONE. Vol. 4. p. e7607. 2004.
-Celi, F. S.; Shuldiner, A. R. The role of peroxisome proliferator-activated receptor gamma in diabetes and obesity. Current Diabetes Reports. Vol. 2. p. 179-185. 2002.
-Chanseaume, E.; colaboradores. Impaired resting muscle energetics studied by31P-NMR in diet-induced obese rats. Journal of Nutrition. Vol.136. p. 2194-2200. 2006.
-Chen, J. F.; colaboradores. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation.Nature Genetics. Vol. 38. p. 228-233. 2006.
-Chen, C.; e colaboradores. Real-time quantification of microRNAs by stem–loop RT–PCR. Nucleic Acids Research. Vol. 33. p. 179. 2005.
-Chen, C. Z.; Lodish, H. F. MicroRNAs as regulators of mammalian hematopoiesis. Seminarsin Immunology. Vol. 17. p. 155-165. 2005.
-Choi, C. S.; e colaboradores. Continuous fat oxidation in acetyl-CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity. Proceedings of National 14
-Academy of Sciences of the United States of America. Vol. 104. p. 16480-16485. 2007.
-Ciolac, E. G.; Guimarães, G. V. Exercício físico e síndrome metabólica. Revista Brasileira de Medicina do Esporte. Vol. 10. p. 319-324. 2004.
-Doench, J.G.; Sharp, P. A. Specificity of microRNA target selection in translational repression. Genes & Development. Vol. 17. p. 438-442. 2003.
-Duncan, B. B.; e colaboradores. Altos coeficientes de mortalidade em populações adultas brasileiras: uma comparação internacional. Revista da Associação Médica Brasileira. Vol. 38. p. 138-144. 1992.
-Edgerton, D. S.; e colaboradores. Effects of insulin on the metabolic control of hepatic gluconeogenesis in vivo. Diabetes. Vol. 58. p. 2766-2775. 2009.
-Eriksson, J.; e colaboradores. Exercise and the metabolic syndrome. Diabetologia. Vol. 40. p. 125-135. 1997.
-Griffin, M. E.; e colaboradores. Free fatty acid-induced insulin resistance is associated with activity of protein kinase C theta and alterations in the insulin signaling pathway. Diabetes, v. 48, p. 1270-1274, 1999.
-Gutteridge, J. M. C. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clinical Chemistry. Vol. 41. p. 1819-1828. 1995.
-Finkel, T. Oxidant signals and oxidative stress. Current Opinion in Cell Biology. Vol. 15. p. 247-254. 2003.
-Finkel, T.; Holbrook, N. J. Oxidants, oxidative stress and the biology of ageing. Nature. Vol. 408. p. 239-247. 2000.
-Gallagher, I.J.; e colaboradores. Integration of microRNA changesin vivoidentifies novel molecular features of muscle insulin resistance in type 2 diabetes. Genome Medicine. Vol. 2. p. 9. 2010.
-Giasson, B. I.; e colaboradores. The relationship between oxidative/nitrative stress and pathological inclusions in Alzheimer’s and Parkinson’s Diseases. Free Radical in Biology and Medicine. Vol. 32. p. 1264-1275. 2002.
-Gilde, A. J.; Van Bilsen, M. Peroxisome proliferator-activated receptors (PPARS): regulators of gene expression in heart and skeletal muscle. Acta Physiologica Scandinavica. Vol. 178. p. 425-434. 2003.
-Guay, C.; e colaboradores. Diabetes mellitus, a microRNA-related disease?Translational Research. Vol. 157. p. 253-264. 2011.
-Hakimi, P.; e colaboradores. Overexpression of the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) in skeletal muscle repatterns energy metabolism n the mouse. Journal of Biological Chemistry. Vol. 282. p. 32844-32855. 2007.
-Hansson, O.; e colaboradores. Transcriptome and proteome analysis of soleus muscle of hormone-sensitive lipase-null mice. Journal of Lipid Research, v. 46, p. 2614-2623, 2005.
-Hawley, J. A.; e colaboradores. Signalling mechanisms in skeletal muscle: role in substrate selection and muscle adaptation. Essays in Biochemistry. Vol. 42. p. 1-12. 2006.
-Hawley, J. A.; e colaboradores. Effect of altering substrate availability on metabolism and performance during intense exercise. Brazilian Journal of Nutrition. Vol. 84. p. 829-838. 2000.
-Herrera, B. M.; e colaboradores. Global microRNA expression profiles in insulin target tissues in a spontaneous rat model of type 2. Diabetologia. Vol. 53. p. 1099-1109. 2010.
-Hirabara, S. M.; e colaboradores. Time-dependent effects of fatty acids on skeletal muscle metabolism. Journal of Cellular Physiology. Vol. 210. p. 7-15. 2007.
-Huppertz, C.; e colaboradores. Uncoupling Protein 3(UCP3) Stimulates Glucose Uptake in Muscle Cells through a Phosphoinositide 3-Kinase-dependent Mechanism. Journal of Biological Chemistry. Vol. 276. p. 12520-12529. 2001.
-Hutvágner, G.; Zamore, P. D. A microRNA in a Multiple-Turnover RNAi Enzyme Complex. Science. Vol. 297. p. 2056-2060. 2002.
-Jenkins, A. B.; e colaboradores. Effects of nonesterified fatty acid availability on tissue-specific glucose utilization in rats in vivo. Journal of Clinical Investigation. Vol. 82. p. 293-299. 1988.
-Karube, Y.; e colaboradores. Reduced expression of Dicer associated with poor prognosis in lung cancer patients. Cancer Science. Vol. 96. p. 111-115. 2005.
-Krek, A.; e colaboradores. Combinatorial microRNA target predictions. Nature Genetics. Vol. 37. p. 495-500. 2005.
-Lambertucci, R. H.; e colaboradores. Palmitate increases superoxide production through mitochondrial electron transport chain and NADPH oxidase activity in skeletal muscle cells.Journal of Cellular Physiology. Vol. 216. p. 796-804. 2008.
-Lee, R. C.; e colaboradores. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. Vol. 3. p. 843-854.1993.
-Lee, Y.; e colaboradores. The nuclear RNase III Drosha initiates microRNA processing. Nature. Vol. 425. p. 415-419. 2003.
-Lewis, B. P.; e colaboradores. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. Vol. 120. p. 15-20. 2005.
-Lim, L. P.; e colaboradores. Vertebrate MicroRNA Genes. Science. Vol. 299. p. 1540. 2003.
-Lin, J.; e colaboradores. Transcriptional co-activator PGC-1[alpha] drives the formation of slow-twitch muscle fibers. Nature. Vol.418. p. 797-801. 2002.
-Lynge, J.; e colaboradores. Extracellular formation and uptake of adenosine during skeletal muscle contraction in the rat: Role of adenosine transporters. Journal of Physiology. Vol. 537. p. 597-1005. 2001.
-Luquet, S.; e colaboradores. Peroxisome proliferator-activated receptor delta controls muscle development and oxidative capability. FASEB Journal. Vol. 17. p. 2299-2301. 2003.
-Mahoney, D. J.; e colaboradores. Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise. FASEB Journal. Vol. 19. p. 1498-1500. 2005.
-Mccarthy, J. J.; e colaboradores. Evidence of MyomiR network regulation of beta-myosin heavy chain gene expression during skeletal muscle atrophy.PhysiologicalGenomics. Vol. 39. p. 219-226.2009.
-Meister, G.; e colaboradores. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Molecular Cell. Vol. 15. p. 185-197. 2004.
-Mette, M. F.; e colaboradores. Transcriptional silencing and promoter methylation triggered by double-stranded RNA. EMBO Journal. Vol. 19. p. 5194-5201. 2000.
-Metzler, M.; e colaboradores. High expression of precursor microRNA-155/BIC RNA in children with Burkitt lymphoma. Genes Chromosomes Cancer. Vol. 39. p. 167-169. 2004.
-Moore, K. J.; e colaboradores. MicroRNAs and cholesterol metabolims. Trends in Endocrinology and Metabology. Vol. 12. p. 699-706. 2010.
-Michael, L. F.; e colaboradores. Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC.Proceedings of National Academy of Sciences of the United States of America. Vol. 98. p. 3820-3825. 2001.
-Muoio, D. M.; Newgard, C. B. Molecular and metabolic mechanisms of insulin resistance and β-cell failure in type 2 diabetes. Nature Reviews Molecular Cell Biology. Vol. 9, p. 193-205, 2008.
-Muoio, D. M.; Koves T. R. Skeletal muscle adaptation to fatty acid depends on coordinated actions of the PPARs and PGC1α: implications for metabolic disease. Journal of Biological Chemistry. Vol. 277. p. 26089-26097. 2002.
-Narkar, V. A.; e colaboradores. AMPK and PPAR delta agonists are exercise mimetics. Cell. Vol. 134. p. 405-414. 2008.
-Nielsen, M.; e colaboradores. MicroRNA identity and abundance in porcine skeletal muscles determined by deep sequencing. Animal Genetics. Vol. 41. p. 159-168. 2010.
-Nilsen, T. W. Mechanisms of microRNA-mediated gene regulation in animal cells. Trends in Genetics. Vol. 23. p. 243-249. 2007.
-Nordberg, J.; Arnér, E. S. J. Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radical in Biology and Medicine. Vol. 31. p. 1287-1312. 2001.
-Petersen, K. F.; e colaboradores. Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes. New England Journal of Medicine. Vol. 350. p. 664-671. 2004.
-Poy, M.; e colaboradores. N. A pancreatic islet-specific microRNA regulates insulin secretion.Nature. Vol. 432. p. 226-230. 2004.
-Puigserver, P.; Spiegelman, B. M. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocrine Reviews. Vol. 24. p. 78-90. 2003.
-Randle, P. J.; e colaboradores. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet I. Vol. 13. p. 785-789. 1963.
-Rezende, E. A.; e colaboradores. Causas múltiplas de morte por doenças crônico-degenerativas: uma análise multidimensional. Caderno de Saúde Pública. Vol. 20. p. 1223-1231. 2004.
-Rodriguez, A.;e colaboradores. Identification of mammalian microRNA host genes and transcription units. Genome Research. Vol.14. p. 1902-1910.2004.
-Ryder, J. W.; e colaboradores. Skeletal muscle reprogramming by activation of calcineurin improves insulin action on metabolic pathways. Journal of Biological Chemistry. Vol. 278. p. 44298-44303. 2003.
-Sabin, M. A.; e colaboradores. Fatty acid-induced defects in insulin signalling, in myotubes derived from children, are related to ceramide production from palmitate rather than the accumulation of intramyocellular lipid. Journal of Cellular Physiology. Vol. 211. p. 244-252. 2007.
-Safdar, A.; e colaboradores. Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice. Proceedings of National Academy of Sciences of the United States of America. Vol. 108. p. 4135-4140. 2011.
-Savage, D. B.; e colaboradores. Disordered lipid metabolism and the pathogenesis of insulin resistance. Physiological Review. Vol. 87. p. 507-520. 2007.
-Scandalios, J. G. Oxidative stress: molecular perception and transduction of signals triggering antioxidant gene defenses. Brazilian Journal of Medical and Biological Research. Vol. 38. p. 995-1014. 2005.
-Sies, H. Oxidative stress: oxidants and antioxidants. Experimental Physiology. Vol. 82. p. 291-295. 1997.
-Silva, C. A.; Lima, W. C. Efeito benéfico do exercício físico no controle metabólico do diabetes mellitus tipo 2 a curto prazo. Arquivos Brasileiros de Endocrinologia e Metabologia. Vol. 46. p. 550-556. 2002.
-Silveira, L. R.; e colaboradores. Updating the effects of fatty acids on skeletal muscle. Journal of Cellular Physiology. Vol. 217. p. 1-12. 2008.
-Silveira, L. R.; e colaboradores. Effect of Lipid Infusion on Metabolism and Force of rat skeletal muscles during intense contractions. Cellular of Physiology and Biochemistry. Vol. 20. p. 213-226. 2007.
-Silveira, L. R.; e colaboradores. Effect of lipid infusion on metabolism and force of rat skeletal muscles during intense contractions. Cellular of Physiology and Biochemistry. Vol. 20. p. 213-226. 2007.
-Silveira, L. R.; e colaboradores. The contraction induced increase in gene expression of peroxisome proliferator-activated receptor (PPAR)-gamma coactivator1α(PGC-1α), mitochondrial uncoupling protein 3 (UCP3) and hexokinase II (HKII) in primary rat skeletal muscle cells is dependent on reactive oxygen species. Biochimica et Biophysica Acta. Vol. 1763. p. 969-976. 2006.
-Tanaka, T.; e colaboradores. Activation of peroxisome proliferator-activated receptor δinduces fatty acid β-oxidation in skeletal muscle and attenuates metabolic syndrome. Proceedings of National Academy of Sciences of the United States of America. Vol. 100. p. 15924-15929. 2003.
-Tang, X.; e colaboradores. Role of microRNAs in diabetes.Biochimica et Biophysica Acta. Vol. 1779. p. 697-701. 2008.
-Van Loon, L. J.; Goodpaster, B. H. Increased intramuscular lipid storage in the insulin-resistant and endurance-trained state.Pflügers Archiv. Vol. 451. p. 606-616. 2006.
-Wahid, F.; e colaboradores. MicroRNAs: synthesis, mechanism, function, and recent clinical trials.Biochimica et Biophysica Acta. Vol. 1803. p. 1231-1243. 2010.
-Wang, Y. X.; e colaboradores. Regulation of muscle fiber type and running endurance by PPARd. PLoS Biology. Vol. 2. p. e294. 2004.
-Wheeler, G.; e colaboradores. In situ detection of animal and plant microRNAs. DNA and Cell Biology. Vol. 26. p. 251-255. 2007.
-Zeng, Y.; e colaboradores. Both natural and designed micro RNAs can inhibit the expression of cognate mRNAs when expressed in human cells. Molecular Cell. Vol. 9. p. 1327-1333. 2002.
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