Crosstalk between tight junction genes and muscle strength: Applying supplement and resistance training to old male wistar rats

Document Type : Original Article

Authors

Department of Exercise Physiology, Faculty of Sport Sciences, University of Guilan, Rasht, Iran.

Abstract

Aim of this study was to determine the relations among the tight junction (TJs) genes, muscle strength and cross-sectional area (CSA) influenced by resistance training with or without specific supplement (a combination of lactobacillus and bifidobacterium probiotics, leucine amino acid and Vitamin-D). For this purpose, 25 male wistar rats in two age groups (3 months in young control and 16-24 months in four other groups) randomly divided in 5 equal groups (old and young control, resistance training, supplement and resistance training plus supplement). After 8 weeks of resistance training trice a week and oral gavage of supplement 5 times per week there were no any relation between grip strength and muscle CSA with zonula occludens-1 (ZO-1) and occludin (Occ) genes. But result of one-way ANOVA revealed that there were significantly differences among study groups in TJs genes, muscle strength and CSA (P≤0.05). Our finding showed that resistance training along with supplement can increase the level of ZO-1 (P=0.011), and Occ genes (P=0.023) expression. Indeed, resistance training plus supplement had synergistic effect on muscle CSA and grip strength (P=0.001) that can be comparable with young group. In addition, supplement alone appears that doesn’t have beneficial impact on physical function but surprisingly our finding shows strong inverse correlation between Occ and grip strength (p=0.015, r= -1.0) in supplement group which implies that although supplement alone can’t improve physical function but can maintain intestinal barrier function.

What is already known on this subject?

Gut-muscle axis is a well-known issue and it is clear that there is strong relation between gut microbiome, muscle function and mass. Each component that can increase SCFA maybe will alleviate inflammation and will decrease level of pro-inflammatory cytokines.

 

What this study adds?

In this study, it was found that although there is a close relationship between intestinal bacterial content and muscle, this relationship is not established between the physical structure of intestinal tight junction and muscle function. There is weak and negative relation between Occ and grip strength that maybe produced by supplement. However, the combination of exercise and supplementation likely be an effective solution to prevent the loss of muscle mass associated with aging and the reduction of the expression of tight junction genes.

Keywords

Main Subjects

Acknowledgements

The authors are grateful to all individuals who contributed to the conducting and process of this study, especially the animal performance laboratory team for their technical support in “Gene and Tissue Laboratory of Pasargad” and Milad Poya Company for providing supplement components.

Funding

None.

Compliance with ethical standards

Conflict of interest The authors declare that they have no conflict of interest.

Ethical approval Animals had free access to standard food and water. All stages of keeping and slaughtering rats were carried out according to the rules of the Animal Ethics Committee of Shahid Beheshti University, Tehran, Iran (ethical code: IR.SBU.REC.1402.052).

Informed consent Animal study.

Author contributions

Conceptualization: H.A., M.M.; Methodology: H.A., M.M.; Software: M.M.; Validation: M.M., Formal analysis; Investigation: H.A, M.M.; Resources: H.A.; Data curation: H.A., M.M.; Writing - original draft: M.M.; Writing – review & editing: H.A.; Visualization: M.M., H.A.; Supervision: H.A. Project administration: M.M.; Funding acquisition: H.A.

References

Al-Sadi, R., Dharmaprakash, V., Nighot, P., Guo, S., Nighot, M., Do, T., & Ma, T. Y. (2021). Bifidobacterium bifidum enhances the intestinal epithelial tight junction barrier and protects against intestinal inflammation by targeting the toll-like receptor-2 pathway in an nf-κb-independent manner. International journal of molecular sciences, 22(15), 8070. doi: https://doi.org/10.3390/ijms22158070
Al-Sadi, R., Khatib, K., Guo, S., Ye, D., Youssef, M., & Ma, T. (2011). Occludin regulates macromolecule flux across the intestinal epithelial tight junction barrier. American Journal of Physiology-Gastrointestinal and Liver Physiology, 300(6), G1054-G1064. doi: https://doi.org/10.1152/ajpgi.00055.2011
Allam-Ndoul, B., Castonguay-Paradis, S., & Veilleux, A. (2020). Gut microbiota and intestinal trans-epithelial permeability. International journal of molecular sciences, 21(17), 6402. doi: https://doi.org/10.3390/ijms21176402
Bhat, A. A., Uppada, S., Achkar, I. W., Hashem, S., Yadav, S. K., Shanmugakonar, M., Uddin, S. (2019). Tight junction proteins and signaling pathways in cancer and inflammation: a functional crosstalk. Frontiers in Physiology, 9, 1942 https://doi.org/10.3389/fphys.2018.01942
Blackwood, B. P., Yuan, C. Y., Wood, D. R., Nicolas, J. D., Grothaus, J. S., & Hunter, C. J. (2017). Probiotic Lactobacillus species strengthen intestinal barrier function and tight junction integrity in experimental necrotizing enterocolitis. Journal of probiotics & health, 5(1). doi: https://doi.org/10.4172/2329-8901.1000159
Bass, J. J., Nakhuda, A., Deane, C. S., Brook, M. S., Wilkinson, D. J., Phillips, B. E., & Atherton, P. J. (2020). Overexpression of the vitamin D receptor (VDR) induces skeletal muscle hypertrophy. Molecular metabolism, 42, 101059. doi: https://doi.org/10.1016/j.molmet.2020.101059
Bollen, S. E., Bass, J. J., Fujita, S., Wilkinson, D., Hewison, M., & Atherton, P. J. (2022). The Vitamin D/Vitamin D receptor (VDR) axis in muscle atrophy and sarcopenia. Cellular signalling, 96, 110355. doi: https://doi.org/10.1016/j.cellsig.2022.110355
Chen, S., Zhang, P., Duan, H., Wang, J., Qiu, Y., Cui, Z., Xie, L. (2023). Gut microbiota in muscular atrophy development, progression and treatment: New therapeutic targets and opportunities. The Innovation. doi: https://doi.org/10.1016/j.xinn.2023.100479
Chen, L. H., Chang, S. S., Chang, H. Y., Wu, C. H., Pan, C. H., Chang, C. C., & Huang, H. Y. (2022). Probiotic supplementation attenuates age‐related sarcopenia via the gut–muscle axis in SAMP8 mice. Journal of cachexia, sarcopenia and muscle, 13(1), 515-531. doi: https://doi.org/10.1002/jcsm.12849
Dalle, S., Rossmeislova, L., & Koppo, K. (2017). The role of inflammation in age-related sarcopenia. Frontiers in Physiology, 8, 1045.
Damiano, S., Muscariello, E., La Rosa, G., Di Maro, M., Mondola, P., & Santillo, M. (2019). Dual role of reactive oxygen species in muscle function: can antioxidant dietary supplements counteract age-related sarcopenia?. International journal of molecular sciences, 20(15), 3815. doi: https://doi.org/10.3390/ijms20153815
De Andrade, I. T., Gualano, B., Hevia-Larraín, V., Neves-Junior, J., Cajueiro, M., Jardim, F., & Roschel, H. (2020). Leucine supplementation has no further effect on training-induced muscle adaptations. Med Sci Sports Exerc, 52(8), 1809-14. doi: https://doi.org/10.1249/MSS.0000000000002307
Dzik, K. P., & Kaczor, J. J. (2019). Mechanisms of vitamin D on skeletal muscle function: oxidative stress, energy metabolism and anabolic state. European journal of applied physiology, 119, 825-839. doi: https://doi.org/10.1007/s00421-019-04104-x
Deldicque, L., Theisen, D., & Francaux, M. (2005). Regulation of mTOR by amino acids and resistance exercise in skeletal muscle. European journal of applied physiology, 94, 1-10. doi: https://doi.org/10.1007/s00421-004-1255-6
Francino, M. P. (2016). Antibiotics and the human gut microbiome: dysbioses and accumulation of resistances. Frontiers in microbiology, 6, 1543.  doi: https://doi.org/10.3389/fmicb.2015.01543
Hornberger Jr, T. A., & Farrar, R. P. (2004). Physiological hypertrophy of the FHL muscle following 8 weeks of progressive resistance exercise in the rat. Canadian journal of applied physiology, 29(1), 16-31. doi: https://doi.org/10.1139/h04-002.
Hsu, T. H., Wu, T. J., Tai, Y. A., Huang, C. S., Liao, J. W., & Yeh, S. L. (2023). The combination of quercetin and leucine synergistically improves grip strength by attenuating muscle atrophy by multiple mechanisms in mice exposed to cisplatin. Plos one, 18(9), e0291462. doi: https://doi.org/10.1371/journal.pone.0291462
Ju, S. H., Lee, E. J., Sim, B. C., Nga, H. T., Lee, H. Y., Tian, J., ... & Yi, H. S. (2023). Leucine-enriched amino acid supplementation and exercise to prevent sarcopenia in patients on hemodialysis: a single-arm pilot study. Frontiers in Nutrition, 10, 1069651. https://doi.org/10.3389/fnut.2023.1069651
Khailova, L., Dvorak, K., Arganbright, K. M., Halpern, M. D., Kinouchi, T., Yajima, M., & Dvorak, B. (2009). Bifidobacterium bifidum improves intestinal integrity in a rat model of necrotizing enterocolitis. American Journal of Physiology-Gastrointestinal and Liver Physiology, 297(5), G940-G949. doi: https://doi.org/10.1152/ajpgi.00141.2009
Lee, M. C., Tu, Y. T., Lee, C. C., Tsai, S. C., Hsu, H. Y., Tsai, T. Y., ... & Huang, C. C. (2021). Lactobacillus plantarum TWK10 improves muscle mass and functional performance in frail older adults: A randomized, double-blind clinical trial. Microorganisms, 9(7), 1466 doiI: https://doi.org/10.3390/microorganisms9071466
Lim, C. H., Gil, J. H., Quan, H., Viet, D. H., & Kim, C. K. (2018). Effect of 8‐week leucine supplementation and resistance exercise training on muscle hypertrophy and satellite cell activation in rats. Physiological reports, 6(12), e13725.  https://doi.org/10.14814/phy2.13725
Ma, J., Piao, X., Mahfuz, S., Long, S., & Wang, J. (2022). The interaction among gut microbes, the intestinal barrier and short chain fatty acids. Animal Nutrition, 9, 159-174. doi: https://doi.org/10.1016/j.aninu.2021.09.012
Martínez-Arnau, F. M., Fonfría-Vivas, R., & Cauli, O. (2019). Beneficial effects of leucine supplementation on criteria for sarcopenia: asystematic review. Nutrients, 11(10), 2504. doi: https://doi.org/10.3390/nu11102504
Meyer, T. N., Schwesinger, C., Ye, J., Denker, B. M., & Nigam, S. K. (2001). Reassembly of the tight junction after oxidative stress depends on tyrosine kinase activity. Journal of Biological Chemistry, 276(25), 22048-22055. doi: https://doi.org/10.1074/jbc.M011477200
Nicastro, H., Zanchi, N. E., da Luz, C. R., de Moraes, W. M., Ramona, P., de Siqueira Filho, M. A., ... & Lancha Jr, A. H. (2012). Effects of leucine supplementation and resistance exercise on dexamethasone-induced muscle atrophy and insulin resistance in rats. Nutrition, 28(4), 465-471. doi: https://doi.org/10.1016/j.nut.2011.08.008
Przewłócka, K., Folwarski, M., Kaźmierczak-Siedlecka, K., Skonieczna-Żydecka, K., & Kaczor, J. J. (2020). Gut-muscle axis exists and may affect skeletal muscle adaptation to training. Nutrients, 12(5), 1451. doi: https://doi.org/10.3390/nu12051451
Prokopidis, K., Giannos, P., Kirwan, R., Ispoglou, T., Galli, F., Witard, O. C., & Isanejad, M. (2023). Impact of probiotics on muscle mass, muscle strength and lean mass: a systematic review and meta‐analysis of randomized controlled trials. Journal of Cachexia, Sarcopenia and Muscle, 14(1), 30-44. https://doi.org/10.1002/jcsm.13132
Rao, R. (2008). Oxidative stress-induced disruption of epithelial and endothelial tight junctions. Frontiers in bioscience: a journal and virtual library, 13, 7210. doi: https://doi.org/10.2741/3223
Sheth, P., Delos Santos, N., Seth, A., LaRusso, N. F., & Rao, R. (2007). Lipopolysaccharide disrupts tight junctions in cholangiocyte monolayers by a c-Src-, TLR4-, and LBP-dependent mechanism. American Journal of Physiology-Gastrointestinal and Liver Physiology, 293(1), G308-G318. doi: https://doi.org/10.1152/ajpgi.00582.2006
Saha, K., Ganapathy, A. S., Wang, A., Morris, N. M., Suchanec, E., Yochum, G & Nighot, P. (2022). Autophagy Increases Occludin Levels to Enhance Intestinal Paracellular Tight Junction Barrier. bioRxiv, 2022-04. doi: https://doi.org/10.1101/2022.04.11.487876
Shin, H. E., Kwak, S. E., Di Zhang, D., Lee, J., Yoon, K. J., Cho, H. S., & Song, W. (2020). Effects of treadmill exercise on the regulation of tight junction proteins in aged mice. Experimental Gerontology, 141, 111077. doi: https://doi.org/10.1016/j.exger.2020.111077
Stio, M., Retico, L., Annese, V., & Bonanomi, A. G. (2016). Vitamin D regulates the tight-junction protein expression in active ulcerative colitis. Scandinavian journal of gastroenterology, 51(10), 1193-1199. doi: https://doi.org/10.1080/00365521.2016.1185463
Takeshita, H., Yamamoto, K., Nozato, S., Inagaki, T., Tsuchimochi, H., Shirai, M., Yokoyama, S. (2017). Modified forelimb grip strength test detects aging-associated physiological decline in skeletal muscle function in male mice. Scientific reports, 7(1), 42323. doi: https://doi.org/10.1038/srep42323
Trabal, J., Forga, M., Leyes, P., Torres, F., Rubio, J., Prieto, E., & Farran-Codina, A. (2015). Effects of free leucine supplementation and resistance training on muscle strength and functional status in older adults: a randomized controlled trial. Clinical Interventions in Aging, 713-723.  doi: https://doi.org/10.2147/CIA.S75271
Uchitomi, R., Oyabu, M., & Kamei, Y. (2020). Vitamin D and sarcopenia: potential of vitamin D supplementation in sarcopenia prevention and treatment. Nutrients, 12(10), 3189. doi: https://doi.org/10.3390/nu12103189
Walston, J. D. (2012). Sarcopenia in older adults. Current opinion in rheumatology, 24(6), 623. doi: https://doi.org/10.1097/BOR.0b013e328358d59b
West, N. P., Pyne, D. B., Cripps, A. W., Hopkins, W. G., Eskesen, D. C., Jairath, A., & Fricker, P. A. (2011). Lactobacillus fermentum (PCC®) supplementation and gastrointestinal and respiratory-tract illness symptoms: a randomised control trial in athletes. Nutrition journal, 10, 1-11. doi: https://doi.org/10.1186/1475-2891-10-30
Zhao, J., Huang, Y., & Yu, X. (2021). A narrative review of gut-muscle axis and sarcopenia: The potential role of gut microbiota. International Journal of General Medicine, 1263-1273. doi: https://doi.org/10.2147/IJGM.S301141
Zhang, J., Vincent, K. P., Peter, A. K., Klos, M., Cheng, H., Huang, S. M., & Ross, R. S. (2020). Cardiomyocyte expression of ZO-1 is essential for normal atrioventricular conduction but does not alter ventricular function. Circulation research, 127(2), 284-297. doi: https://doi.org/10.1161/CIRCRESAHA.119.315539
Zuhl, M., Schneider, S., Lanphere, K., Conn, C., Dokladny, K., & Moseley, P. (2014). Exercise regulation of intestinal tight junction proteins. British journal of sports medicine, 48(12), 980-986. doi: https://doi.org/10.1136/bjsports-2012-091585
Zhao, J., Zhao, Y., Liu, H., Cao, Q., Feng, L., Zhang, Z., & Jiang, J. (2023). Dietary Leucine Improves Fish Intestinal Barrier Function by Increasing Humoral Immunity, Antioxidant Capacity, and Tight Junction. International Journal of Molecular Sciences, 24(5), 4716. doi: https://doi.org/10.3390/ijms24054716
Journal of Exercise & Organ Cross Talk
Volume 3, Issue 4
December 2023
Pages 173-182

Files

History

  • Receive Date: 16 October 2023
  • Revise Date: 24 December 2023
  • Accept Date: 30 December 2023

Share

How to cite

Statistics