Resistance training reduces FTO gene expression in subcutaneous adipose tissue and improves glycemic control in diabetic rats

Document Type : Original Article

Authors

1 Exercise Physiology, Department of Physical Education, Saveh Branch, Islamic Azad University, Saveh, Iran

2 Associate Professor of Exercise Physiology, Department of Physical Education, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran. ORCID: 0000 0002 5963 2323

Abstract

Fat mass and obesity-associated gene (FTO) is directly associated with increased risk of obesity and type 2 diabetes mellitus (T2DM). The purpose of current study was to investigate the effect of 12 weeks of resistance training (RT) on FTO expression in subcutaneous adipose tissue, glucose, and insulin levels in T2DM rats. Sixteen males Wistar rats (220±10 gr) with T2DM induced by streptozotocin-nicotinamide injection were randomly assigned into resistance training (RT; n=8) and control (Con; n=8) groups. RT was performed for 12 weeks, 5 days per week. FTO expression in subcutaneous adipose tissue, fasting blood glucose (FBS), insulin and insulin resistance (HOMA-IR) were measured 48 hours after the last exercise training session.   After the exercise training intervention, the FTO expression (p=0.004) and FBS (p=0.001) were significantly lower in the RT compared to the Con group while the insulin in the RT was significantly higher than that in the Con group (p=0.001). There was no significant difference in the insulin resistance between the two groups (p˃0.05). According to findings, it seems that RT can decrease FBS and FTO expression in subcutaneous adipose tissue of T2DM rats. Improved blood glucose in diabetic rats might be partially attributed to reduced FTO expression in response to RT.   

What is already known on this subject?

Excessive body fat mass may cause diabetes and some metabolic disorders. Body fat percentage managements may improve diabetes.

 

What this study adds?

Resistance exercise training can decrease fasting blood glucose and FTO expression in subcutaneous adipose tissue of T2DM rats.

Keywords

Main Subjects

Acknowledgement

This article is taken from the Master's thesis in exercise physiology from Islamic Azad University, Saveh Branch. We are grateful to all those who cooperated with us in this research.

Funding

None.

Compliance with ethical standards

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

Ethical approval This study has been approved by the Ethics Committee of the Research Institute of Physical Education and Sports Sciences with code IR.SSRI.REC.1400.1028.

Informed consent Animal study.

Author contributions

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

References

Bodaghabadi, Z., Mohammadi, L., Halabchi, F., Tavakol, Z., Kluzek, S., Rajabian Tabesh, M. … Alizadehet, Z. (2023). Effects of high-dairy versus low-dairy, high-protein and low-calorie diets combined with aerobic exercise on central body fat in overweight women: A pragmatic randomized controlled trial. Obesity Medicine, 40, 100492. doi: https://doi.org/10.1016/j.obmed.2023.100492.
Borse, S.P., Chhipa, A.S., Sharma, V., Singh, D.P., & Nivsarkar, M. (2021). Management of type 2 diabetes: Current strategies, unfocussed aspects, challenges, and alternatives. Medical Principles and Practice, 30(2), 109-121. doi: http://doi.org/10.1159/000511002.
Botezelli, J.D., Coope, A., Ghezzi, A.C., Cambri, L.T., Moura, L.P., Scariot, P.P., … Pauli1, J. R. (2016). Strength training prevents hyperinsulinemia, insulin resistance, and inflammation independent of weight loss in fructose-fed animals. Scientific Reports, 4(6), 31106. doi: http://doi.org/10.1038/srep31106.
Bravard, A., Veilleux, A., Disse, E., Laville, M., Vidal, H., Tchernof, A., & Rieusset, J. (2013). The expression of FTO in human adipose tissue is influenced by fat depot, adiposity, and insulin sensitivity. Obesity (Silver Spring), 21(6), 1165-73. doi: http://doi.org/10.1002/oby.20110.
 Bronczek, G.A., Soares, G.M., de Barros, J.F., Vettorazzi J.F., Kurauti, M.A., Marconato-Júnior, E. … Costa-Júnior, J.M. (2021). Resistance exercise training improves glucose homeostasis by enhancing insulin secretion in C57BL/6 mice. Scientific Reports, 21 (1), 8574. doi: http://doi.org/10.1038/s41598-021-88105-x.
Celis-Morales, C., Marsaux, C.F., Livingstone, K.M., Navas-Carretero, S., San-Cristobal, R., O'donovan, C.B…. Mathers, J.  (2016). Physical activity attenuates the effect of the FTO genotype on obesity traits in European adults: The Food4Me study. Obesity (Silver Spring), 24(4), 962-9. doi: http://doi.org/10.1002/oby.21422.
Chauhdary, Z., Rehman, K., & Akash, M.S.H. (2021). The composite alliance of FTO locus with obesity-related genetic variants. Clinical and Experimental Pharmacology and Physiology, 48(7), 954-965. doi: http://doi.org/10.1111/1440-1681.13498.
Danaher, J., Stathis, C.G., Wilson, R.A., Moreno-Asso, A., Wellard, R.M., & Cooke, M.B. (2020). High intensity exercise downregulates FTO mRNA expression during the early stages of recovery in young males and females. Nutrition & Metabolism, 17(17), 68. doi: http://doi.org/10.1186/s12986-020-00489-1.
Eizadi. M., Ravasi, A.A., Soory, R., Baesi, K., & Choobineh, S. (2016). The effect of three months of resistance training on TCF7L2 expression in pancreas tissues of type 2 diabetic rats. Avicenna Journal of Medical Biochemistry, 4(1), e34014. doi: http://doi.org/10.17795/ajmb-34014.
Fan, H.Q., He, W., Xu, K.F., Wang, Z.X., Xu, X.Y., & Chen, H. (2015). FTO inhibits insulin secretion and promotes NF-κB activation through positively regulating ROS production in pancreatic β cells. PLoS One, 10(5), e0127705.
Frayling, T.M., Timpson, N.J., Weedon, M.N., Zeggini, E., Freathy, R.M., Lindgren, C.M…. McCarthy, M.I. (2007). A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science, 316, 889-94. doi: http://doi.org/10.1126/science.1141634.
Galicia-Garcia, U., Benito-Vicente, A., Jebari, S. … Martín, C. (2020). Pathophysiology of type 2 diabetes mellitus. International Journal of Molecular Sciences, 21(17), 6275. Doi: http://doi.org/10.3390/ijms21176275.
Jun-Ho, L. (2018). Comprehensive relevance of AMPK in adaptive responses of physical exercise, skeletal muscle and neuromuscular disorders. Journal of the Korean Society of Physical Medicine, 13(3), 141-150. doi: https://doi.org/10.13066/kspm.2018.13.3.141
Kalhor, H., Peeri, M., Matinhomaee, H., & Izadi, M. (2018). The effect of 6 weeks resistance training and HITT on GLP-1 gene expression of diabetic rats. Iranian Journal of Diabetes and Obesity, 10 (1), 42-49. URL: https://ijdo.ssu.ac.ir/article-1-384-.pdf
Kang, Y., Liu, F., & Liu, Y. (2017). Is FTO gene variant related to cancer risk independently of adiposity? An updated meta-analysis of 129,467 cases and 290,633 controls. Oncotarget, 8(31), 50987-50996. doi: http://doi.org/10.18632/oncotarget.16446
Kim, J.Y. (2021). Optimal diet strategies for weight loss and weight loss maintenance. Journal of Obesity & Metabolic Syndrome, 30(1), 20-31.doi: http://doi.org/10.7570/jomes20065.
Kushkestani, M., Parvani, M., Moghadassi, M., & Baradaran, R. (2022).The effect of six -week high -intensity interval training on muscle expression of FTO and PPAR -γ in obese diabetic rats. Iranian Journal of Health Sciences, 10(2), 29 -39.
Kwak, S.H., & Park, K.S. (2018). Pathophysiology of type 2 diabetes in Koreans. Endocrinology and Metabolism (Seoul), 33(1), 9-16. doi: https://doi.org/10.3803/EnM.2018.33.1.9
Lan, N., Lu, Y., Zhang, Y., Pu, S., Xi, H., Nie, X…. Yuan, W. (2020). FTO: A common genetic basis for obesity and cancer. Frontiers in Genetics, 11, 559138. doi: https://doi.org/10.3389/fgene.2020.559138
Mambiya, M., Shang, M., Wang, Y., Li, Q., Liu, S., Yang, L…. Liu, W. (2019). The play of genes and non-genetic factors on type 2 diabetes. Front Public Health, 7, 349. doi: https://doi.org/10.3389/fpubh.2019.00349
Oza, M.J., & Kulkarni, Y.A. (2018). Formononetin treatment in type 2 diabetic rats reduces insulin resistance and hyperglycaemia. Frontiers in Pharmacology, 9, 739. doi: https://doi.org/10.3389/fphar.2018.00739
Scuteri, A., Sanna, S., Chen, W-M., Uda, M., Albai, G., Strait, J… Abecasis, G.R. (2007). Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLOS Genetics, 3, e115. doi: https://doi.org/10.1371/journal.pgen.0030115
Shill, L., Alam, M., Chowdhury, A., & Alam, S. (2021). Association of FTO gene (rs9939609) with obesity and type-2 diabetes mellitus: Review from current studies. Romanian Journal of Diabetes Nutrition and Metabolic Disease, 28(4), 447-52. URL: http://www.rjdnmd.org/index.php/RJDNMD/article/view/890.
Tavakol, L., & Nematolahzadeh Mahani, M. (2019). Effects of resistance training on insulin resistance and pancreatic beta-cells function in male patients with type 2 diabetes. Journal of Physical Activity and Hormones, 3(1), 19-34. URL: https://journals.iau.ir/article_665357.html
Tucker, L.A., Tucker, J.M., Bailey, B.W., & LeCheminant, J.D. (2015). Dietary patterns as predictors of body fat and BMI in women: A factor analytic study. American Journal of Health Promotion, 29(4), e136-46. doi: http://doi.org/10.4278/ajhp.130327-QUAN-129.
Vieira, R.F.L., Junqueira, R.L., Gaspar, R.C., Muñoz, V.R., & Pauli, J.R. (2020). Exercise activates AMPK signalling: The impact on glucose uptake in the skeletal muscle in aging. Journal of Rehabilitation Therapy, 2(2), 48-53.
Wang, Q., Wang, J., Lin, H., Huo, X., Zhu, Q., & Zhang, M. (2018). Relationship between fat mass and obesity-associated gene expression and type 2 diabetes mellitus severity. Experimental and Therapeutic Medicine, 15(3), 2917-2921. doi: https://doi.org/10.3892/etm.2018.5752
Wu, W., Feng, J., Jiang, D., Zhou, X., Jiang, Q., Cai, M., … Wang, Y. (2017) .AMPK regulates lipid accumulation in skeletal muscle cells through FTO-dependent demethylation of N6-methyladenosine. Scientific Reports, 7, 41606. URL: https://link.springer.com/content/pdf/10.1038/srep41606.pdf
Yang, Y., Liu, B., Xia, W., Yan, J., Liu, H.Y., Hu, L., & Li, S. (2017). FTO genotype and type 2 diabetes mellitus: Spatial analysis and meta-analysis of 62 case-control studies from different regions. Genes (Basel), 8(2), 70. doi: https://doi.org/10.3390/genes8020070
Yazdanpazhooh, S., Banaeifar, A., Arshadi, S., & Eizadi, M. (2018).Six weeks resistance training effect on FTO expression in type ii diabetes rats. Iranian Journal of Diabetes and Obesity, 10 (4), 216-222.
 
Journal of Exercise & Organ Cross Talk
Volume 3, Issue 2
June 2023
Pages 81-85

Files

History

  • Receive Date: 11 April 2023
  • Revise Date: 03 June 2023
  • Accept Date: 11 June 2023

Share

How to cite

Statistics