Effectiveness of Exercise and Sex Interaction on Adipokines in Obese Rats

  • Made Mahaguna Putra Doctoral Student of Medical Sciences, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia
  • Muchsin Doewes Faculty of Medicine, Universitas Sebelas Maret
  • Bambang Purwanto Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia
  • Dono Indarto Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia
  • Hasta Handayani Idrus Center for Biomedical Research, Research Organization for Health, National Research and Innovation Agency (BRIN), Jakarta, Indonesia
Keywords: Obesity, Inflammation, Exercise, Adipokines, Sex

Abstract


Background/Aim: Obesity is a low-grade chronic inflammatory state that promotes a pro-inflammatory immune response. Exercise is considered to be able to prevent inflammation in obesity. The main objective was to determine the effect of the interaction between exercise and sex on inflammation and adipokine in obese rats.

Methods: This research is an experiment using a factorial design with a post-test only. The subjects of this study were 30 Sprague Dawley rats. The rats were 4 months old and weighed 120 g. The rats were given a diet high in carbohydrates and fats. The measurement of obese rats used Lee's obesity index. The obese rats were then randomly divided into six groups to be given exercise interventions. The intervention provided consisted of aerobic exercise and anaerobic exercise. The primary outcome is adiponectin, leptin, dipeptidyl peptidase-4 (DPP4), tumour necrosis factor alpha (TNF-α) and adipose tissue hypertrophy.

Results: The study found that increased serum adiponectin levels were influenced by exercise (p < 0.05) and the interaction between exercise and gender (p < 0.05). Decreased serum leptin levels were influenced by gender (p < 0.05) and exercise (p < 0.05). Decreased serum DPP4 levels were influenced by exercise (p < 0.05). Decreased TNF-α expression was influenced by gender (p < 0.05) and the interaction between gender and exercise (p < 0.05). Decreased adipose cell size was influenced by gender (p < 0.05).

 

Conclusion: This study found that aerobic exercise, anaerobic exercise and the interaction between sex and exercise significantly increased serum adiponectin and decreased TNF-α expression.

 

References

Cooke AA, Connaughton RM, Lyons CL, McMorrow AM, Roche HM. Fatty acids and chronic low grade inflammation associated with obesity and the metabolic syndrome. Eur J Pharmacol. 2016 Aug 15;785:207-14. doi: 10.1016/j.ejphar.2016.04.021.

Bairwa SK, Kumari S, Khandelwal N, Kumar Dhaked G, Dhaked S, Bhatt R. Obesity: an important predictor of metabolic syndrome. Scr Med 2023 Mar;54(1):81-5. doi: 10.5937/scriptamed54-40389.

Coelho M, Oliveira T, Fernandes R. Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci. 2013;9(2):191–200. doi: 10.5114/aoms.2013.33181.

Ye J. Mechanisms of insulin resistance in obesity. Front Med China. 2013;7(1):14–24. doi: 10.1007/s11684-013-0262-6.

Wei Y, Chen K, Whaley-Connell AT, Stump CS, Ibdah JA, Sowers JR. Skeletal muscle insulin resistance: role of inflammatory cytokines and reactive oxygen species. Am J Physiol Regul Integr Comp Physiol. 2008 Mar;294(3):R673-80. doi: 10.1152/ajpregu.00561.2007.

Leal V de O, Mafra D. Adipokines in obesity. Clin Chim Acta 2013;419:87–94. doi: 10.1016/J.CCA.2013.02.003.

Shin SK, Song SE, Oh JU, Hwang M, Cho HW, Bae JH, et al. Orexin A-induced inhibition of leptin expression and secretion in adipocytes reducing plasma leptin levels and hypothalamic leptin resistance. Pflugers Arch. 2019 Dec;471(11-12):1407-18. doi: 10.1007/s00424-019-02318-8.

Romacho T, Sell H, Indrakusuma I, Roehrborn D, Castañeda TR, Jelenik T, et al. DPP4 deletion in adipose tissue improves hepatic insulin sensitivity in diet-induced obesity. Am J Physiol Endocrinol Metab. 2020 May 1;318(5):E590-E599. doi: 10.1152/ajpendo.00323.2019.

Varin EM, Mulvihill EE, Beaudry JL, Pujadas G, Fuchs S, Tanti JF, et al. Circulating levels of soluble dipeptidyl peptidase-4 are dissociated from inflammation and induced by enzymatic DPP4 inhibition. Cell Metab. 2019 Feb 5;29(2):320-334.e5. doi: 10.1016/j.cmet.2018.10.001..

Gleeson M, Bishop NC, Stensel DJ, Lindley MR, Mastana SS, Nimmo MA. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol. 2011 Aug 5;11(9):607-15. doi: 10.1038/nri3041.

Ghoshal K, Bhattacharyya M. Adiponectin: Probe of the molecular paradigm associating diabetes and obesity. World J Diabetes. 2015;6(1):151. doi: 10.4239/WJD.V6.I1.151.

Stanford KI, Middelbeek RJW, Goodyear LJ. Exercise effects on white adipose tissue: Beiging and metabolic adaptations. Diabetes. 2015;64(7):2361–8. doi: 10.2337/db15-0227.

Lee MC, Chung YC, Thenaka PC, Wang YW, Lin YL, Kan NW. Effects of different HIIT protocols on exercise performance, metabolic adaptation, and fat loss in middle-aged and older adults with overweight. Int J Med Sci. 2024 Jun 24;21(9):1689-1700. doi: 10.7150/ijms.96073.

Nieman DC, Wentz LM. The compelling link between physical activity and the body’s defense system. J Sport Heal Sci. 2018;8(3):201. doi: 10.1016/J.JSHS.2018.09.009.

Smith GI, Mittendorfer B, Klein S. Metabolically healthy obesity: facts and fantasies. J Clin Invest. 2019;129(10):3978. doi: 10.1172/JCI129186.

Warburton DER, Nicol CW, Bredin SSD. Health benefits of physical activity: the evidence. CMAJ 2006;174(6):801–9. doi: 10.1503/CMAJ.051351.

Mitsui R, Fukushima M, Taniguchi A, Nakai Y, Aoyama S, Takahashi Y, et al. Insulin secretory capacity and insulin sensitivity in impaired fasting glucose in Japanese. J Diabetes Investig. 2012 Aug 20;3(4):377-83. doi: 10.1111/j.2040-1124.2012.00201.x.

Imazu AA, Goessler KF, Casonatto J, Polito MD. The influence of physical training status on postexercise hypotension in patients with hypertension: a cross-sectional study. Blood Press Monit. 2017 Aug;22(4):196-201. doi: 10.1097/MBP.0000000000000255.

Batista ML Jr, Rosa JC, Lopes RD, Lira FS, Martins E Jr, Yamashita AS, et al. Exercise training changes IL-10/TNF-alpha ratio in the skeletal muscle of post-MI rats. Cytokine. 2010 Jan;49(1):102-8. doi: 10.1016/j.cyto.2009.10.007.

Tan X, Chapman CD, Cedernaes J, Benedict C. Association between long sleep duration and increased risk of obesity and type 2 diabetes: A review of possible mechanisms. Sleep Med Rev. 2018 Aug;40:127-34. doi: 10.1016/j.smrv.2017.11.001.

Collins LM, Dziak JJ, Kugler KC, Trail JB. Factorial experiments: efficient tools for evaluation of intervention components. Am J Prev Med. 2014 Oct;47(4):498-504. doi: 10.1016/j.amepre.2014.06.021.

Shaw R, Festing MF, Peers I, Furlong L. Use of factorial designs to optimize animal experiments and reduce animal use. ILAR J. 2002;43(4):223-32. doi: 10.1093/ilar.43.4.223.

Ilyas M, Adzim M, Simbak N, Baig A. sample size calculation for animal studies using degree of freedom (e); an easy and statistically defined approach for metabolomics and genetic research. Curr Trends Biomed Eng Biosci 2017;10(2):1–2. doi: 10.19080/ctbeb.2017.10.555785.

Damasceno DC, Sinzato YK, Bueno A, Dallaqua B, Lima PH, Calderon IM, et al. Metabolic profile and genotoxicity in obese rats exposed to cigarette smoke. Obesity (Silver Spring). 2013 Aug;21(8):1596-601. doi: 10.1002/oby.20152.

Campos KE, Volpato GT, Calderon IM, Rudge MV, Damasceno DC. Effect of obesity on rat reproduction and on the development of their adult offspring. Braz J Med Biol Res. 2008 Feb;41(2):122-5. doi: 10.1590/s0100-879x2008005000001.

King AJF. The use of animal models in diabetes research. Br J Pharmacol. 2012;166(3):877–94. doi: 10.1111/j.1476-5381.2012.01911.x.

Qiao D, Hou L, Liu X. Influence of intermittent anaerobic exercise on mouse physical endurance and antioxidant components. Br J Sports Med. 2006;40(3):214–8. doi: 10.1136/bjsm.2005.020099.

Li NC, Wei XX, Hu YL, Hou X, Xu H. Aerobic exercise blocks interleukin-6 levels and germ cell apoptosis in obese rats. Andrologia. 2018 Mar;50(2). doi: 10.1111/and.12880.

Shaodong C, Haihong Z, Manting L, Guohui L, Zhengxiao Z, Y M Z. Research of influence and mechanism of combining exercise with diet control on a model of lipid metabolism rat induced by high fat diet. Lipids Health Dis. 2013 Feb 20;12:21. doi: 10.1186/1476-511X-12-21.

Jiménez-Maldonado A, Montero S, Lemus M, Cerna-Cortés J, Rodríguez-Hernández A, Mendoza MA, et al. Moderate and high intensity chronic exercise reduces plasma tumor necrosis factor alpha and increases the Langerhans islet area in healthy rats. J Musculoskelet Neuronal Interact. 2019 Sep 1;19(3):354-61. PMID: 31475943.

Macêdo Santiago LÂ, Neto LGL, Borges Pereira G, Leite RD, Mostarda CT, de Oliveira Brito Monzani J, et al. Effects of resistance training on immunoinflammatory response, tnf-alpha gene expression, and body composition in elderly women. J Aging Res. 2018 Oct 28;2018:1467025. doi: 10.1155/2018/1467025.

Rejeki PS, Pranoto A, Rahmanto I, Izzatunnisa N, Yosika GF, Hernaningsih Y, et al. The positive effect of four-week combined aerobic-resistance training on body composition and adipokine levels in obese females. Sports (Basel). 2023 Apr 20;11(4):90. doi: 10.3390/sports11040090.

Peng J, Yin L, Wang X. Central and peripheral leptin resistance in obesity and improvements of exercise. Horm Behav. 2021;133. doi: 10.1016/J.YHBEH.2021.105006.

Bharath LP, Choi WW, Cho JM, Skobodzinski AA, Wong A, Sweeney TE, et al. Combined resistance and aerobic exercise training reduces insulin resistance and central adiposity in adolescent girls who are obese: randomized clinical trial. Eur J Appl Physiol. 2018 Aug;118(8):1653-1660. doi: 10.1007/s00421-018-3898-8.

Simoes E, Correia-Lima J, Sardas L, Storti F, Otani TZDS, Vasques DAC, et al. Sex dimorphism in inflammatory response to obesity in childhood. Int J Obes (Lond). 2021 Apr;45(4):879-887. doi: 10.1038/s41366-021-00753-1.

Garekani ET, Mohebbi H, Kraemer RR, Fathi R. Exercise training intensity/volume affects plasma and tissue adiponectin concentrations in the male rat. Peptides. 2011 May;32(5):1008-12. doi: 10.1016/j.peptides.2011.01.027.

Amirazodi M, Mehrabi A, Rajizadeh MA, Bejeshk MA, Esmaeilpour K, Daryanoosh F, et al. The effects of combined resveratrol and high intensity interval training on the hippocampus in aged male rats: An investigation into some signaling pathways related to mitochondria. Iran J Basic Med Sci. 2022 Feb;25(2):254-62. doi: 10.22038/IJBMS.2022.57780.12853.

Rajizadeh MA, Sheibani V, Bejeshk MA, Mohtashami Borzadaran F, Saghari H, Esmaeilpour K. The effects of high intensity exercise on learning and memory impairments followed by combination of sleep deprivation and demyelination induced by etidium bromide. Int J Neurosci. 2019 Dec;129(12):1166-78. doi: 10.1080/00207454.2019.1640695.

Rajizadeh MA, Esmaeilpour K, Haghparast E, Ebrahimi MN, Sheibani V. Voluntary exercise modulates learning & memory and synaptic plasticity impairments in sleep deprived female rats. Brain Res. 2020 Feb 15;1729:146598. doi: 10.1016/j.brainres.2019.146598.

Liu K, Zhao W, Li C, Tian Y, Wang L, Zhong J, Yan X, Wang Y, Wang L, Wang H. The effects of high-intensity interval training on cognitive performance: a systematic review and meta-analysis. Sci Rep. 2024 Dec 30;14(1):32082. doi: 10.1038/s41598-024-83802-9.

Rajizadeh MA, Moslemizadeh A, Hosseini MS, Rafiei F, Soltani Z, Khoramipour K. Adiponectin receptor 1 could explain the sex differences in molecular basis of cognitive improvements induced by exercise training in type 2 diabetic rats. Sci Rep. 2023 Sep 27;13(1):16267. doi: 10.1038/s41598-023-43519-7.

Chang E, Varghese M, Singer K. Gender and sex differences in adipose tissue. Curr Diab Rep. 2018;18(9). doi: 10.1007/S11892-018-1031-3.

Landen S, Voisin S, Craig JM, McGee SL, Lamon S, Eynon N. Genetic and epigenetic sex-specific adaptations to endurance exercise. Epigenetics. 2019 Jun;14(6):523-535. doi: 10.1080/15592294.2019.1603961.

Lebeck J, Østergård T, Rojek A, Füchtbauer EM, Lund S, Nielsen S, et al. Gender-specific effect of physical training on AQP7 protein expression in human adipose tissue. Acta Diabetol. 2012 Dec;49 Suppl 1:S215-26. doi: 10.1007/s00592-012-0430-1.

Diniz TG, Silva AS, Dos Santos Nunes MK, Ribeiro MD, Filho JM, do Nascimento RAF, et al. Physical activity level influences MTHFR gene methylation profile in diabetic patients. Front Physiol. 2021 Jan 12;11:618672. doi: 10.3389/fphys.2020.618672.

Da Mota GR, Orsatti FL, Delbin MA, Zanesco A. Resistance exercise improves metabolic parameters and changes adipocyte-derived leptin: a comparison between genders in untrained adults. Mot Rev Educ Física. 2016;22(3):217–22. doi: 10.1590/S1980-6574201600030014.

Becic T, Studenik C, Hoffmann G. Exercise increases adiponectin and reduces leptin levels in prediabetic and diabetic individuals: systematic review and meta-analysis of randomized controlled trials. Med Sci. 2018;6(4). doi: 10.3390/MEDSCI6040097.

González-Jurado JA, Suárez-Carmona W, López S, Sánchez-Oliver AJ. Changes in lipoinflammation markers in people with obesity after a concurrent training program: a comparison between men and women. Int J Environ Res Public Health. 2020 Aug 25;17(17):6168. doi: 10.3390/ijerph17176168.

Published
2025/10/31
Section
Original article