The effect of aerobic training and stevia supplement on expression of the glucose metabolism signaling pathway markers in heart tissue of obese rats

authors:

avatar Zahra Akbari , avatar Asieh Abbassi Daloii ORCID , * , avatar Ahmad Abdi ORCID , avatar sayed javad ziaolhagh

Koomesh: Vol.25, issue 3; 339-349
published online: September 09, 2023
article type: Research Article
received: February 02, 2023
accepted: August 09, 2023

how to cite: Akbari Z, Abbassi Daloii A, Abdi A, ziaolhagh S J. The effect of aerobic training and stevia supplement on expression of the glucose metabolism signaling pathway markers in heart tissue of obese rats. koomesh. 2023;25(3):e152832. 

Abstract

Introduction: Obesity is associated with dysfunction in the metabolic processes of heart tissue, and genetic factors are associated with metabolic homeostasis of heart tissue. This study aimed to evaluate the effect of aerobic training and stevia supplements on the expression of the glucose metabolism signaling pathway markers in the heart tissue of obese rats. Materials and Methods: For the implementation of this experimental research, 25 male Wistar rats (five healthy adult rats and 20 adult obese male rats) were divided into five groups: control (healthy), obese, obese-stevia, obese-aerobic training, and obese-stevia- -aerobic training. Aerobic exercise was performed on a treadmill, five days a week for eight weeks. Supplemental groups received 250 mg of stevia (per kilogram of body weight) by gavage during the intervention period. After anesthesia, an autopsy was performed and heart tissue was removed. gene expression of mTOR, AKT, PI3K ، IRS2، INSR, and PTEN in heart tissue were measured using Real-Time PCR. Results: After the intervention, a decrease of mTOR and PTEN gene expression and an increase of IRS2 and PI3K gene expression in heart tissue were observed in all intervention groups compared to the obese group (P=0.001). Also, the increase of AKT gene expression and the decrease of INSR gene expression in heart tissue were prominent in the obese + exercise + stevia group compared to the obese group (P=0.001). Conclusion: It seems that aerobic training and stevia supplementation can help to improve the factors involved in heart energy metabolism during obesity.

References

  • 1.

    Lam BC, Lim AY, Chan SL, Yum MP, Koh NS, Finkelstein EA. The impact of obesity: a narrative review. Singapore Med J 2023; 64: 163-171.

  • 2.

    Pagidipati NJ, Zheng Y, Green JB, McGuire DK, Mentz RJ, Shah S, et al. Association of obesity with cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease: Insights from TECOS. Am Heart J 2020; 219: 47-57.

  • 3.

    Buono F, Crispo S, Pagano G, Rengo G, Petitto M, Grieco F, et al. Determinants of left ventricular hypertrophy in patients with recent diagnosis of essential hypertension. J Hypertens 2014; 32: 166-173.

  • 4.

    Fontana L, Klein S, Holloszy JO. Effects of long-term calorie restriction and endurance exercise on glucose tolerance, insulin action, and adipokine production. Age (Dordr) 2010; 32: 97-108.

  • 5.

    Chanda D, Luiken JJ, Glatz JF. Signaling pathways involved in cardiac energy metabolism. FEBS Lett 2016; 590: 2364-2374.

  • 6.

    Costa MM, Violato NM, Taboga SR, Ges RM, Bosqueiro JR. Reduction of insulin signalling pathway IRS-1/IRS-2/AKT/mTOR and decrease of epithelial cell proliferation in the prostate of glucocorticoid-treated rats. Int J Exp Pathol 2012; 93: 188-195.

  • 7.

    Gray S, Kim JK. New insights into insulin resistance in the diabetic heart. Trends Endocrinol Metab 2011; 22: 394-403.

  • 8.

    Savova MS, Mihaylova LV, Tews D, Wabitsch M, Georgiev MI. Targeting PI3K/AKT signaling pathway in obesity. Biomed Pharmacother 2023; 159: 114244.

  • 9.

    Gupta A, Dey CS. PTEN, a widely known negative regulator of insulin/PI3K signaling, positively regulates neuronal insulin resistance. Mol Biol Cell 2012; 23: 3882-3898.

  • 10.

    Beauchamp EM, Platanias LC. The evolution of the TOR pathway and its role in cancer. Oncogene 2013; 32: 3923.

  • 11.

    Bathina S, Das UN. Dysregulation of PI3K-Akt-mTOR pathway in brain of streptozotocin-induced type 2 diabetes mellitus in Wistar rats. Lipids Health Dis 2018; 17: 168.

  • 12.

    Madani P, avandy SM, Haghshenas R, Pakdel A. Combined effect of eight weeks high intensity resistance training with ginger supplementation on waist to hip ratio, body composition and body mass in obese women. Koomesh 2017; 19: 289-293. (Persian).

  • 13.

    Moghadam E, Eskandari Z, Shiri Shahsavar MR, Mirmoezzi M. Effects of high-intensity interval and mini-trampoline training with calorie restriction on body composition and aerobic capacity in overweight and obese women. Koomesh 2022; 24: 747-756. (Persian).

  • 14.

    Egan B, Zierath JR. Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab 2013; 17: 162-184.

  • 15.

    Platt C, Houstis N, Rosenzweig A. Using exercise to measure and modify cardiac function. Cell Metab 2015; 21: 227-236.

  • 16.

    Gayda M, Ribeiro PA, Juneau M, Nigam A. Comparison of different forms of exercise training in patients with cardiac disease: where does high-intensity interval training fit? Can J Cardiol 2016; 32: 485-494.

  • 17.

    Gsiorowski A, Dutkiewicz J. Comprehensive rehabilitation in chronic heart failure. Ann Agric Environ Med 2013; 20: 606-612.

  • 18.

    Ray J, Kumar S, Laor D, Shereen N, Nwamaghinna F, Thomson A, et al. Effects of stevia rebaudiana on glucose homeostasis, blood pressure and inflammation: a critical review of past and current research evidence. Int J Clin Res Trials 2020; 5: 142.##https://doi.org/10.15344/2456-8007/2020/142.

  • 19.

    Anbazhagan M, Kalpana M, Rajendran R, Natarajan V, Dhanave D. In vitro production of Stevia rebaudiana Bertoni. Emir J Food Agric 2010; 22: 216-222.##https://doi.org/10.9755/ejfa.v22i3.4891.

  • 20.

    Rojas E, Bermdez V, Motlaghzadeh Y, Mathew J, Fidilio E, Faria J, et al. Stevia rebaudiana bertoni and its effects in human disease: emphasizing its role in inflammation, atherosclerosis and metabolic syndrome. Curr Nutr Rep 2018; 7: 161-170.

  • 21.

    Salesi M, Mehrtash M, Daryanoosh F, Tanide N. The role of caloric restriction on lipid coat proteins gene expression and insulin resistance after 8 weeks high caloric diet in male rats. J Arak Uni Med Sci 2018; 21: 21-31 (Persian).

  • 22.

    Sahrapour A, Akbarzadeh S, Bargahi A, Rahbar A. Evaluation of the effect of stevia on serum safety in STZ diabetic rats. thesis, Bushehr Univ Med Sci Health Serv 2013. (Persian).

  • 23.

    Cho DK, Choi DH, Cho JY. Effect of treadmill exercise on skeletal muscle autophagy in rats with obesity induced by a high-fat diet. J Exerc Nutr Biochem 2017; 21: 26-34.

  • 24.

    Ma Z, Qi J, Meng S, Wen B, Zhang J. Swimming exercise training-induced left ventricular hypertrophy involves microRNAs and synergistic regulation of the PI3K/AKT/mTOR signaling pathway. Eur J Appl Physiol 2013; 113: 2473-2486.

  • 25.

    Wallace MA, Hughes DC, Baar K. mTORC1 in the control of myogenesis and adult skeletal muscle mass. In Mol Med mTOR 2016; 37-56.##https://doi.org/10.1016/B978-0-12-802733-2.00025-6.

  • 26.

    Showkat M, Beigh MA, Andrabi KI. mTOR signaling in protein translation regulation: implications in cancer genesis and therapeutic interventions. Mol Biol Int 2014; 2014: 686984.

  • 27.

    Sato S, Kataoka S, Sato M, Takahashi A, Norikura T, Mukai Y. Effect of Bangle (Zingiber purpureum) extract and low-intensity exercise on mTOR phosphorylation and autophagy flux in skeletal muscles of rats on a high-fat diet. J Funct Foods 2018; 47: 554-561.##https://doi.org/10.1016/j.jff.2018.06.010.

  • 28.

    Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell 2017; 168: 960-976.

  • 29.

    Ghigo A, Laffargue M, Li M, Hirsch E. PI3K and calcium signaling in cardiovascular disease. Circ Res 2017; 121: 282-292.

  • 30.

    Harrison CL, Lombard CB, Moran LJ, Teede HJ. Exercise therapy in polycystic ovary syndrome: a systematic review. Hum Reprod Update 2011; 17: 171-183.

  • 31.

    Choi K, Kim YB. Molecular mechanism of insulin resistance in obesity and type 2 diabetes. Korean J Intern Med 2010; 25: 119-129.

  • 32.

    Oliveira AG, Carvalho BM, Tobar N, Ropelle ER, Pauli JR, Bagarolli RA, et al. Physical exercise reduces circulating lipopolysaccharide and TLR4 activation and improves insulin signaling in tissues of DIO rats. Diabetes 2011; 60: 784-796.

  • 33.

    Lencu C, Nicula R, Lotrean ML. Hormonal response to physical exercise. Palestrica of the third millennium - Civilization and Sport. 2016; 56-60.

  • 34.

    Cheng Z, Tseng Y, White MF. Insulin signaling meets mitochondria in metabolism. Trends Endocrinol Metab 2010; 21: 589-598.

  • 35.

    Zhao X, An X, Yang C, Sun W, Ji H and Lian F. The crucial role and mechanism of insulin resistance in metabolic disease. Front. Endocrinol 2023; 14: 1149239.

  • 36.

    Stiles BL. PI-3-K and AKT: Onto the mitochondria. Adv Drug Deliv Rev 2009; 61: 1276-1282.

  • 37.

    Weeks KL, Gao X, Du XJ, Boey EJ, Matsumoto A, Bernardo BC, et al. Phosphoinositide 3-kinase p110 is a master regulator of exercise-induced cardioprotection and PI3K gene therapy rescues cardiac dysfunction. Circ Heart Fail 2012; 5: 523-534.

  • 38.

    Machrina Y, AL-Rasyid Damanik H, 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. J Health Sci 2018; 4: 50-56.

  • 39.

    Matsuda S, Nakanishi A, Wada Y, Kitagishi Y. Roles of PI3K/AKT/PTEN pathway as a target for pharmaceutical therapy. Open Med Chem J 2013; 7: 23-29.

  • 40.

    Ohno K, Okuda K, Uehara T. Endogenous S-sulfhydration of PTEN helps protect against modification by nitric oxide. Biochem Biophys Res Commun 2015; 456: 245-249.

  • 41.

    Khokhar M, Purohit P, Tomo S, Agarwal RG, Gadwal A, Bajpai NK, et al. PTEN, MMP2, and NF-B and regulating microRNA-181 aggravate insulin resistance and progression of diabetic nephropathy: a case-control study. Kidney Dialysis 2023; 3: 121-138.##https://doi.org/10.3390/kidneydial3010011.

  • 42.

    Goyal SK, Samsher, Goyal RK. Stevia (Stevia rebaudiana) a bio-sweetener: a review. Int J Food Sci Nutr 2010; 61: 1-10.

  • 43.

    Ahmad U, Ahmad RS. Anti-diabetic property of aqueous extract of Stevia rebaudiana Bertoni leaves in Streptozotocin-induced diabetes in albino rats. BMC Complement Altern Med. 2018; 18: 179.