The Pattern of Peroxisome Proliferator-activated Receptor Gamma Coactivator 1-alpha Gene Expression in Type-2 Diabetes Mellitus Rat Model Liver: Focus on Exercise
DOI:
https://doi.org/10.3889/oamjms.2021.6362Keywords:
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha, Liver, Type-2 diabetes mellitus, Rat, ExerciseAbstract
BACKGROUND: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) has an important role in mitochondria biogenesis which generated cellular metabolism. Carbohydrate metabolism in the liver is crucial to maintain plasma blood glucose.
AIM: This research aimed to determine the expression of PGC-1α gene in the liver type-2 diabetes mellitus (T2DM) rat model, after treatment with a focus on exercise.
METHODS: We used 25 healthy male Wistar rats as subjects. Rats were modified to T2DM models by feeding a high-fat diet and low-dose streptozotocin injection. We divided the rats into five groups, that is, sedentary group as a control and four others as treatment groups. The exercise was assigned for treatment groups by a run on the treadmill as moderate intensity continuous (MIC), highintensity continuous (HIC), slow interval (SI), and fast interval (FI). The treatment groups were exercise throughout 8 weeks with a frequency of 3 times a week.
RESULTS: The results showed that expression of PGC-1α gene was lower in all treatment groups compared to controls (p < 0.05). Expression in HIC was higher than MIC (p < 0.05), so was the expression in FI more than SI (p < 0.05).
CONCLUSIONS: Exercise affected PGC-1α gene expression in the liver of the T2DM rat model. The expression of PGC-1α was linear with exercise intensity.
Downloads
Metrics
Plum Analytics Artifact Widget Block
References
Soewondo P, Ferrario A, Tahapary DL. Challenges in diabetes management in Indonesia: A literature review. Global Health. 2013;9(1):63. https://doi.org/10.1186/1744-8603-9-63 PMid:24299164
Indonesian Ministry of Health. Laporan Nasional Riset Kesehatan Dasar 2018. The Indonesian Ministry of Health’s National Research and Development Agency; 2019. Available from: http://www.labmandat.litbang.depkes.go.id/images/download/laporan/rkd/2018/laporan_nasional_rkd2018_final.pdf. https://doi.org/10.17501/24246735.2018.4105
Liang H, Ward WF. PGC-1α: A key regulator of energy metabolism. Adv Physiol Educ. 2006;30(4):145-51. PMid:17108241
Finck BN, Kelly DP. PGC-1 coactivators: Inducible regulators of energy metabolism in health and disease. J Clin Invest. 2006;116(3):615-22. https://doi.org/10.1172/jci27794 PMid:16511594
Puigserver P, Spiegelman BM. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): Transcriptional coactivator and metabolic regulator. Endocr Rev. 2003;24(1):78-90. https://doi.org/10.1210/er.2002-0012 PMid:12588810
Setyawati T. Peroxisome proliferator activated receptor-γ (Ppar-γ) coactivator 1-α (PGC-1 α) in type 2 Diabetes Mellitus and its role in mitochondrial function. Med Tadulako. 2014;1(1):54-62.
Corona JC, Duchen MR. PPAR gamma and PGC-1alpha as therapeutic targets in Parkinson’s. Neurochem Res. 2015;40(2):308-16. PMid:25007880
Wu H, Deng X, Shi Y, Su Y, Wei J, Duan H. PGC-1α, glucose metabolism and Type 2 diabetes mellitus. J Endocrinol. 2016;229(3):R99-115. https://doi.org/10.1530/joe-16-0021 PMid:27094040
Sugden MI, Caton PW, Holness MJ. PPAR control: It’s SIRTainly as easy as PGC. J Endocrinol. 2010;204(2):93-104. https://doi.org/10.1677/joe-09-0359 PMid:19770177
Kim JA, Wei Y, Sowers JR. Role of mitochondrial dysfunction in insulin resistance. Circ Res. 2008;102(4):401-14. PMid:18309108
Łukaszuk B, Kurek K, Mikłosz A, Żendzian-Piotrowska M, Chabowski A. The role of PGC-1α in the development of insulin resistance in skeletal muscle-revisited. Cell Physiol Biochem. 2015;37(6):2288-96. https://doi.org/10.1159/000438584 PMid:26625097
Li N, Brun T, Cnop M, Cunha DA, Eizirik DL, Maechler P. Transient oxidative stress damages mitochondrial machinery inducing persistent beta-cell dysfunction. J Biol Chem. 2009;284(35):23602-12. https://doi.org/10.1074/jbc.m109.024323 PMid:19546218
Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003;34(3):267-73. https://doi.org/10.1038/ng1180 PMid:12808457
Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S, et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proc Natl Acad HICi USA. 2003;100(14):8466-71. https://doi.org/10.1073/pnas.1032913100 PMid:12832613
Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell. 1998;92(6):829-39. https://doi.org/10.1016/s0092-8674(00)81410-5
Leick L, Fentz J, Biensø RS, Knudsen JG, Jeppesen J, Kiens B, et al. PGC-1α is required for AICAR-induced expression of GLUT4 and mitochondrial proteins in mouse skeletal muHICle. Am J Physiol Endocrinol Metab. 2010;299(3):E456-65. https://doi.org/10.1152/ajpendo.00648.2009 PMid:20628026
Safdar A, Little JP, Stokl AJ, Hettinga BP, Akhtar M, Tarnopolsky MA. Exercise increases mitochondrial PGC-1α content and promotes nuclear-mitochondrial cross-talk to coordinate mitochondrial biogenesis. J Biol Chem. 2011;286(12):10605-17. https://doi.org/10.1074/jbc.m110.211466 PMid:21245132
Buler M, Aatsinki SM, Skoumal R, Komka Z, To M, Kerkela R, et al. Energy-sensing factors coactivator peroxisome proliferator-activated receptor coactivator 1-α (PGC-1α) and AMP-activated protein kinase control expression of inflammatory mediators in liver induction of interleukin 1 receptor antagonist. J Biol Chem. 2012;287(3):1847-60. https://doi.org/10.1074/jbc.m111.302356 PMid:22117073
Huang AM, Jen CJ, Chen HF, Yu L, Kuo YM, Chen HI. Compulsive exercise acutely upregulates rat hippocampal brain-derived neurotrophic factor. J Neural Transm (Vienna). 2006;113(7):803-11. https://doi.org/10.1007/s00702-005-0359-4 PMid:16252072
Kelley DE, He J, Menshikova EV, and Ritov VB. Dysfunction of mitochondria in human skeletal muscle in Type 2 diabetes. Diabetes. 2002;51(10):2944-50. https://doi.org/10.2337/diabetes.51.10.2944 PMid:12351431
Liang H, Balas B, Tantiwong P, Dube J, Goodpaster BH, O’Doherty RM, et al. Whole body overexpression of PGC-1 α has opposite effects on hepatic and muscle insulin sensitivity. Am J Physiol Endocrinol Metab. 2009;296(4):E945-54. https://doi.org/10.1152/ajpendo.90292.2008 PMid:19208857
Lin J, Handshin C, Spiegelman BM. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab. 2005;1(6):361-70. PMid:16054085
Marinho R, Mekary RA, Muñoz VR, Gomes RJ, Pauli JR, de Moura LP. Regulation of hepatic TRB3/Akt interaction induced by physical exercise and its effect on the hepatic glucose production in an insulin resistance state. Diabetol Metab Syndr. 2015;7:67. https://doi.org/10.1186/s13098-015-0064-x PMid:26288661
Huertas JR, Casuso RA, Agustín PH, Cogliati S. Stay fit, stay young: Mitochondria in movement: The role of exercise in the new mitochondrial paradigm. Oxid Med Cell Longev. 2019;2019:7058350. https://doi.org/10.1155/2019/7058350 PMid:31320983
Haase TN, Ringholm S, Leick L, Biensø RS, Kiilerich K, Johansen S, et al. Role of PGC-1α in exercise and fasting-induced adaptations in mouse liver. Am J Physiol Regul Integr Comp Physiol. 2011;301(5):R1501-9. https://doi.org/10.1152/ajpregu.00775.2010 PMid:21832205
Liang H, Bai Y, Li Y, Richardson A, Ward WF. PGC-1α-induced mitochondrial alterations in 3T3 fibroblast cells. Ann N Y Acad Sci. 2007;1100(1):264-79. PMid:17460188
Machrina Y, Harun AL, Purba A, Lindarto D. Effect various type of exercise to Insr gene expression, skeletal muscle insulin receptor and insulin resistance on diabetes mellitus type-2 model rats. Int J Health Sci. 2018;6(4):50-6.
Matiello R, Fukui RT, Silva ME, Rocha DM, Wajchenberg BL, Azhar S, et al. Differential regulation of PGC-1α expression in rat liver and skeletal muscle in response to voluntary running. Nutr Metab (Lond). 2010;7(1):36. https://doi.org/10.1186/1743-7075-7-36 PMid:20433743
Downloads
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2021 Yetty Machrina, Dharma Lindarto, Yunita Sari Pane, Novita Sari Harahap (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0)
