Journal of Kerman University of Medical Sciences

The Effect of High-Intensity Interval Training in the Presence of L-Carnitine on the Expression of MCT1, PGC-1, and CS in the Liver of Male Wistar Rats

Document Type : Original Article

Authors

Mahdiyeh Haj Hosseini 1
Beydolah Shahouzehi 2
Najmeh Sadat Hosseini 3, 4

1 Department of Physical Education and Sport Science,National University of Skills(NS),Tehran, Iran

2 Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

3 Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

4 Department of Exercise Physiology, Faculty of Sports Sciences, Shahid Bahonar University of Kerman, Kerman, Iran

https://doi.org/10.34172/jkmu.2024.37
Abstract
Background: T Liver oxidative metabolism disorder is dependent on several factors that lead to liver diseases like non-alcoholic fatty liver disease. Our hypothesis was that the combination of high-intensity interval training (HIIT) and L-carnitine affects the expression of citrate synthase (CS), PGC-1α, and monocarboxylate transporter 1 (MCT1) in the liver of male Wistar rats.
Methods: Thirty-two male Wistar rats were divided into four groups (n=8): control, L-carnitine (200 mg/kg/d, four weeks, IP), HIIT, and HIIT+L-carnitine (200 mg/kg/d, four weeks, IP). HIIT training was performed for four weeks (five days a week); then, the animals were anesthetized, and their liver tissues were extracted for real-time PCR to measure MCT1, PGC-1α, and CS. SPSS 22 software was used to analyze the data obtained in different groups, with P<0.05 considered statistically significant.
Results: MCT1 expression significantly increased in the HIIT and HIIT+L-carnitine groups compared to the control group (P<0.001). PGC- 1α expression significantly increased in the HIIT+L-carnitine group compared to the control and L-carnitine groups (P<0.001). Also, PGC- 1α expression significantly increased in the HIIT group compared to the control group (P<0.001). Furthermore, CS expression significantly increased in all groups compared to the control group (P<0.001).
Conclusion: HIIT exercise combined with L-carnitine supplementation increases the expression of MCT1, PGC-1α, and CS in the liver. Therefore, it seems that performing HIIT exercises and taking L-carnitine supplements can prevent the consequences of fat accumulation in the liver.
 

Keywords

High-intensity interval training
MCT1
PGC-1α
CS gene
Subjects
  1. Zhang S, Hulver MW, McMillan RP, Cline MA, Gilbert ER. The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility. Nutr Metab (Lond). 2014;11(1):10. doi: 10.1186/1743-7075-11-10.
  2. Randle PJ. Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. Diabetes Metab Rev. 1998;14(4):263-83. doi: 10.1002/ (sici)1099-0895(199812)14:4<263::aid-dmr233>3.0.co;2-c.
  3. Bielefeld DR, Vary TC, Neely JR. Inhibition of carnitine palmitoyl-CoA transferase activity and fatty acid oxidation by lactate and oxfenicine in cardiac muscle. J Mol Cell Cardiol. 1985;17(6):619-25. doi: 10.1016/s0022-2828(85)80030-4.
  4. Mootha VK, Bunkenborg J, Olsen JV, Hjerrild M, Wisniewski JR, Stahl E, et al. Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria. Cell. 2003;115(5):629-40. doi: 10.1016/s0092-8674(03)00926-7.
  5. Campos CV, Teixeira CJ, Payolla TB, Crisma AR, Murata GM, Amaral AG, et al. Changes in PGC-1α-dependent mitochondrial biogenesis are associated with inflexible hepatic energy metabolism in the offspring born to dexamethasonetreated mothers. Livers. 2021;1(4):201-20. doi: 10.3390/ livers1040016.
  6. Rius-Pérez S, Torres-Cuevas I, Millán I, Ortega Á L, Pérez S. PGC-1α, inflammation, and oxidative stress: an integrative view in metabolism. Oxid Med Cell Longev. 2020;2020:1452696. doi: 10.1155/2020/1452696.
  7. Estall JL, Kahn M, Cooper MP, Fisher FM, Wu MK, Laznik D, et al. Sensitivity of lipid metabolism and insulin signaling to genetic alterations in hepatic peroxisome proliferatoractivated receptor-gamma coactivator-1alpha expression. Diabetes. 2009;58(7):1499-508. doi: 10.2337/db08-1571.
  8. Droździk M, Szeląg-Pieniek S, Grzegółkowska J, ŁapczukRomańska J, Post M, Domagała P, et al. Monocarboxylate transporter 1 (MCT1) in liver pathology. Int J Mol Sci. 2020;21(5):1606. doi: 10.3390/ijms21051606.
  9. Latham CM, Fenger CK, White SH. Rapid communication: differential skeletal muscle mitochondrial characteristics of weanling racing-bred horses. J Anim Sci. 2019;97(8):3193-8. doi: 10.1093/jas/skz203.
  10. Liu HW, Kao HH, Wu CH. Exercise training upregulates SIRT1 to attenuate inflammation and metabolic dysfunction in kidney and liver of diabetic db/db mice. Nutr Metab (Lond). 2019;16:22. doi: 10.1186/s12986-019-0349-4.
  11. Savic D, Hodson L, Neubauer S, Pavlides M. The importance of the fatty acid transporter L-carnitine in non-alcoholic fatty liver disease (NAFLD). Nutrients. 2020;12(8):2178. doi: 10.3390/nu12082178.
  12. Cha YS. Effects of L-carnitine on obesity, diabetes, and as an ergogenic aid. Asia Pac J Clin Nutr. 2008;17 Suppl 1:306-8.
  13. Eskandari HG, Cimen MY, Tamer L, Kanik A, Atik U. Short term effects of L-carnitine on serum lipids in STZ-induced diabetic rats. Diabetes Res Clin Pract. 2004;66(2):129-32. doi: 10.1016/j.diabres.2004.03.005.
  14. Karim S, Adams DH, Lalor PF. Hepatic expression and cellular distribution of the glucose transporter family. World J Gastroenterol. 2012;18(46):6771-81. doi: 10.3748/wjg.v18. i46.6771.
  15. Holloszy JO, Coyle EF. Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. J Appl Physiol Respir Environ Exerc Physiol. 1984;56(4):831-8. doi: 10.1152/jappl.1984.56.4.831.
  16. Pala R, Genc E, Tuzcu M, Orhan C, Sahin N, Er B, et al. L-carnitine supplementation increases expression of PPAR-γ and glucose transporters in skeletal muscle of chronically and acutely exercised rats. Cell Mol Biol (Noisy-le-grand). 2018;64(1):1-6. doi: 10.14715/cmb/2018.64.1.1.
  17. Jabbari E, Gholami M, Nikbakht H, Shakeri N, Ghazaliyan F. Effect of aerobic training and L-carnitine supplementation on some apoptotic factors in diabetic rat liver. Razi J Med Sci. 2019;26(7):131-40. [Persian].
  18. Hoene M, Lehmann R, Hennige AM, Pohl AK, Häring HU, Schleicher ED, et al. Acute regulation of metabolic genes and insulin receptor substrates in the liver of mice by one single bout of treadmill exercise. J Physiol. 2009;587(1):241-52. doi: 10.1113/jphysiol.2008.160275.
  19. Carnevali LC Jr, Eder R, Lira FS, Lima WP, Gonçalves DC, Zanchi NE, et al. Effects of high-intensity intermittent training on carnitine palmitoyl transferase activity in the gastrocnemius muscle of rats. Braz J Med Biol Res. 2012;45(8):777-83. doi: 10.1590/s0100-879x2012007500105.
  20. Holloway TM, Bloemberg D, da Silva ML, Quadrilatero J, Spriet LL. High-intensity interval and endurance training are associated with divergent skeletal muscle adaptations in a rodent model of hypertension. Am J Physiol Regul Integr Comp Physiol. 2015;308(11):R927-34. doi: 10.1152/ ajpregu.00048.2015.
  21. Muniyappa R. Oral carnitine therapy and insulin resistance. Hypertension. 2010;55(2):e13. doi: 10.1161/ hypertensionaha.109.147504.
  22. Patel J, Goyal R, Bhatt P. Beneficial effects of levo-carnitine on lipid metabolism and cardiac function in neonatal streptozotocin rat model of diabetes. Int J Diabetes Metab. 2008;16(1):29-34. doi: 10.1159/000497650.
  23. Rahbar AR, Shakerhosseini R, Saadat N, Taleban F, Pordal A, Gollestan B. Effect of L-carnitine on plasma glycemic and lipidemic profile in patients with type II diabetes mellitus. Eur J Clin Nutr. 2005;59(4):592-6. doi: 10.1038/sj.ejcn.1602109.
  24. Leeuwenburgh C, Hollander J, Leichtweis S, Griffiths M, Gore M, Ji LL. Adaptations of glutathione antioxidant system to endurance training are tissue and muscle fiber specific. Am J Physiol. 1997;272(1 Pt 2):R363-9. doi: 10.1152/ ajpregu.1997.272.1.R363.
  25. Marefati H, Masoumi-Ardakani Y, Shakerian S, Habibi A, Aminizadeh S, Shahouzehi B. The effects of pyruvate dehydrogenase kinase 4 (PDK4) inhibition on metabolic flexibility during endurance training in skeletal muscles of streptozotocin-induced diabetic rats. J Kerman Univ Med Sci. 2020;27(4):304-17. doi: 10.22062/jkmu.2020.91017.
  26. Yap KH, Yee GS, Candasamy M, Tan SC, Md S, Abdul Majeed AB, et al. Catalpol ameliorates insulin sensitivity and mitochondrial respiration in skeletal muscle of type-2 diabetic mice through insulin signaling pathway and AMPK/SIRT1/ PGC-1α/PPAR-γ activation. Biomolecules. 2020;10(10):1360. doi: 10.3390/biom10101360.
  27. Lim K, Jang J. L‐carnitine supplement and running training improve skeletal muscle recovery after hindlimb suspension induced muscle atrophy. FASEB J. 2017;31(S1):799-6. doi: 10.1096/fasebj.31.1_supplement.799.6.
  28. Cantó C, Auwerx J. PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr Opin Lipidol. 2009;20(2):98-105. doi: 10.1097/ MOL.0b013e328328d0a4.
  29. 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 (1985). 2007;102(2):616-21. doi: 10.1152/ japplphysiol.00590.2006.
  30. Shahouzehi B, Nasri H, Aminizadeh S, Masoumi-Ardakani Y. The effect of high-intensity interval training and L-carnitine on the expression of some pro-inflammatory genes in the liver and cardiac tissues of rats. J Kerman Univ Med Sci. 2021;28(1):56- 68. doi: 10.22062/jkmu.2021.91564.
  31. Lezi E, Lu J, Selfridge JE, Burns JM, Swerdlow RH. Lactate administration reproduces specific brain and liver exerciserelated changes. J Neurochem. 2013;127(1):91-100. doi: 10.1111/jnc.12394.
  32. Wang G, Zhao L, Jiang Q, Sun Y, Zhao D, Sun M, et al. Intestinal OCTN2- and MCT1-targeted drug delivery to improve oral bioavailability. Asian J Pharm Sci. 2020;15(2):158-73. doi: 10.1016/j.ajps.2020.02.002.
  33. Gyawali A, Hyeon SJ, Ryu H, Kang YS. The alteration of L-carnitine transport and pretreatment effect under glutamate cytotoxicity on motor neuron-like NSC-34 lines. Pharmaceutics. 2021;13(4):551. doi: 10.3390/ pharmaceutics13040551.
  34. Merrill JF, Thomson DM, Hardman SE, Hepworth SD, Willie S, Hancock CR. Iron deficiency causes a shift in AMPactivated protein kinase (AMPK) subunit composition in rat skeletal muscle. Nutr Metab (Lond). 2012;9(1):104. doi: 10.1186/1743-7075-9-104.
  35. Vigelsø A, Andersen NB, Dela F. The relationship between skeletal muscle mitochondrial citrate synthase activity and whole-body oxygen uptake adaptations in response to exercise training. Int J Physiol Pathophysiol Pharmacol. 2014;6(2):84- 101.
  36. Cochran AJ, Percival ME, Tricarico S, Little JP, Cermak N, Gillen JB, et al. Intermittent and continuous high-intensity exercise training induce similar acute but different chronic muscle adaptations. Exp Physiol. 2014;99(5):782-91. doi: 10.1113/expphysiol.2013.077453.
Journal of Kerman University of Medical Sciences
Volume 31, Issue 5
September and October 2024
Pages 238-242

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