Approaches to correct thyroid status in female rats with visceral obesity

Obesity can lead to thyroid dysfunction in male rats, as shown in our primary studies. The aim of this work was to study the morpho-functional state of the thyroid gland in diet-induced visceral obesity and variants of its non-drug correction in female Wistar rats.

The experiments involved six groups of animals. Rats were fed either a standard diet (StD) or a high-calorie diet (HCD), which induced visceral obesity. Obesity was corrected by switching from HCD to StD and/or by treadmill running. The following animal groups were utilized in the study: 1) “StD” – 16 weeks; 2) “HCD” – 16 weeks; 3) “HCD/StD” – 8/8 weeks; 4) “StD + running” – 16/8 weeks; 5) “HCD + running” – 16/8 weeks; 6) “HCD/StD + running” – 8/8 weeks.

An increase in thyroxine (T4) levels was observed in the blood serum of female rats in the HCD group. At the same time, thyroperoxidase (TPO) activity and malonic dialdehyde (MDA) content in thyroid tissue decreased, and morphological signs of thyroid hypofunction were observed. The most complete recovery of TPO activity and morpho-functional characteristics of thyroid tissue was observed during the transition from HCD to StD. Moderate physical activity against the background of HCD had a positive effect on some morphometric characteristics of the thyroid, but did not restore the values of TPO and MDA. With combined correction of obesity (HCD/StD + running), a partial restoration of the organ histostructure with normalisation of TPO activity, but not MDA, was observed.

Thus, diet-induced visceral obesity is accompanied by an increase in blood thyroxine levels, yet morphological and biochemical signs of decreased functional activity of the thyroid gland tissue develop. A successful correction of visceral obesity, accompanied by the restoration of thyroid structure and function, can be achieved by transitioning from HCD to StD.

1. Biondi B. Subclinical Hypothyroidism in Patients with Obesity and Metabolic Syndrome: A Narrative Review. Nutrients, 2023, vol. 16, no. 1, art. 87, pp. 1–13. https://doi.org/10.3390/nu16010087

2. Sych Yu. P., Fadeev V. V., Mel’nichenko G. A., Syrkin A. L., Roitman A. P. Disorders of lipid metabolism in subclinical hypothyroidism. Problemy Endokrinologii [Problems of Endocrinology], 2004, vol. 50, no. 3, pp. 48–52 (in Russian). https://doi.org/10.14341/probl11429

3. Walczak K., Sieminska L. Obesity and Thyroid Axis. International Journal of Environmental Research and Public Health, 2021, vol. 18, no. 18, art. 9434, pp. 1–23. https://doi.org/10.3390/ijerph18189434

4. Ciloglu F., Peker I., Pehlivan A., Karacabey K., Ilhan N., Saygin O., Ozmerdivenli R. Exercise intensity and its effects on thyroid hormones. Neuroendocrinology Letters, 2005, vol. 26, no. 6, pp. 830–834.

5. Roa Dueñas O. H., Koolhaas C., Voortman T., Franco O. H., Ikram M. A., Peeters R. P., Chaker L. Thyroid Function and Physical Activity: A Population-Based Cohort Study. Thyroid, 2021, vol. 31, no. 6, pp. 870–875. https://doi.org/10.1089/thy.2020.0517

6. Bansal A., Kaushik A., Singh C. M., Sharma V., Singh H. The effect of regular physical exercise on the thyroid function of treated hypothyroid patients: An interventional study at a tertiary care center in Bastar region of India. Archives of Medicine and Health Sciences, 2015, vol. 3, no. 2, pp. 244–246. https://doi.org/10.4103/2321-4848.171913

7. Fathi M., Mosaferi Ziaaldini M., Khairabadi S., Hejazi K. Effect of Aerobic Exercise on Thyroid Hormones and Quality of Life in Obese Postmenopausal Women. Medical Laboratory Journal, 2018, vol. 12, no. 6, pp. 5–11. https://doi.org/10.29252/mlj.12.6.5

8. Klasson C. L., Sadhir S., Pontzer H. Daily physical activity is negatively associated with thyroid hormone levels, inflammation, and immune system markers among men and women in the NHANES dataset. PLoS One, 2022, vol. 17, no. 7, art. e0270221, pp. 1–15. https://doi.org/10.1371/journal.pone.0270221

9. Duñabeitia I., González-Devesa D., Varela-Martínez S., Diz-Gómez J. C., Ayán-Pérez C. Effect of physical exercise in people with hypothyroidism: systematic review and meta-analysis. Scandinavian Journal of Clinical and Laboratory Investigation, 2023, vol. 83, no. 8, pp. 523–532. https://doi.org/10.1080/00365513.2023.2286651

10. Patel H., Alkhawam H., Madanieh R., Shah N., Kosmas C. E., Vittorio T. J. Aerobic vs anaerobic exercise training effects on the cardiovascular system. World Journal of Cardiology, 2017, vol. 9, no. 2, pp. 134–138. https://doi.org/10.4330/wjc.v9.i2.134

11. Sheptulina A. F., Golubeva Yu. A., Drapkina O. M. Fructose consumption as a risk factor for metabolic syndrome and nonalcoholic fatty liver disease. Dokazatel’naya gastroenterologiya [Russian Journal of evidence-based Gastroenterology], 2023, vol. 12, no. 1, pp. 85–92 (in Russian). https://doi.org/10.17116/dokgastro20231201185

12. Gileva O. G., Butolin E. G., Tereshchenko M. V., Ivanov V. G. Evaluation of indicators of carbohydrate and lipid metabolism in rats depending on the type of high-calorie diet. Ozhirenie i metabolizm [Obesity and metabolism], 2022, vol. 19, no. 1, pp. 47–52 (in Russian). https://doi.org/10.14341/omet12712

13. Yanko R. V., Chaka E. G., Zinchenko A. S., Safonov S. L., Levashov M. I. Features of modeling fatty liver disease in rats of different ages based on a high-calorie diet. Ozhirenie i metabolizm [Obesity and metabolism], 2021, vol. 18, no. 4, pp. 387–397 (in Russian). https://doi.org/10.14341/omet12789

14. Gancheva S., Zhelyazkova-Savova M., Galunska B., Chervenkov T. Experimental models of metabolic syndrome in rats. Scripta Scientifica Medica, 2015, vol. 47, no. 2, pp. 14–21. http://dx.doi.org/10.14748/ssm.v47i2.1145

15. Wang R., Tian H., Guo D., Tian Q., Yao T., Kong X. Impacts of exercise intervention on various diseases in rats. Journal of Sport and Health Science, 2020, vol. 9, no. 3, pp. 211–227. https://doi.org/10.1016/j.jshs.2019.09.008

16. Marcondes F. K., Miguel K. J., Melo L. L., Spadari-Bratfisch R. C. Estrous cycle influences the response of female rats in the elevated plus-maze test. Physiology & Behavior, 2001, vol. 74, no. 4–5, pp. 435–440. https://doi.org/10.1016/S0031-9384(01)00593-5

17. Stal’naya I. D., Garishvili T. G. Method for the determination of malondialdehyde using thiobarbituric acid. Sovre­ mennye metody v biokhimii [Modern methods in biochemistry], Moscow, 1977, pp. 66–68 (in Russian).

18. Mityukova T. A., Chudilovskaya E. N., Migalevich A. S. Determination of Thyroid Peroxidase Activity in the Thyroid Tissue of Rats (Experimental Study). Laboratornaya diagnostika. Vostochnaya Evropa [Laboratory diagnostics. Eastern Europe], 2020, vol. 9, no. 3, pp. 285–293 (in Russian). https://doi.org/10.34883/PI.2020.9.3.009

19. Mityukova T. A., Chudilovskaya E. N., Basalai A. A. Activity of Type I Iodothyronine 5ʹ-Deiodinase in the Liver in Rats Receiving a High-Calorie Diet (Experimental Study). Laboratornaya diagnostika. Vostochnaya Evropa [Laboratory diagnostics. Eastern Europe], 2022, vol. 11, no. 1, pp. 60–68 (in Russian). https://doi.org/10.34883/PI.2022.11.1.016

20. Gereben B., Zeöld A., Dentice M., Salvatore D., Bianco A. C. Activation and inactivation of thyroid hormone by deiodinases: Local action with general consequences. Cellular and Molecular Life Sciences, 2008, vol. 65, no. 4, pp. 570–590. https://doi.org/10.1007/s00018-007-7396-0

21. Chawla S., Jena S. The Anatomy and Physiology of Laboratory Rat. Essentials of Laboratory Animal Science: Principles and Practices, 2021, pp. 187–209. https://doi.org/10.1007/978-981-16-0987-9_9

22. Carvalho D. P., Dupuy C. Thyroid hormone biosynthesis and release. Molecular and Cellular Endocrinology, 2017, vol. 458, pp. 6–15. https://doi.org/10.1016/j.mce.2017.01.038

23. Shao S.-S., Zhao Y.-F., Song Y.-F., Xu C., Yang J.-M., Xuan S.-M., Yan H. L., Yu C.-X., Zhao M., Xu J., Zhao J.-J. Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats. Acta Pharmacologica Sinica, 2014, vol. 35, no. 11, pp. 1411–1420. https://doi.org/10.1038/aps.2014.82

24. Mityukova T. A., Kuznetsova T. E., Basalai A. A., Chudilovskaya E. N., Polulyakh O. E., Shcherbakov Ya. V., Khrustaleva T. A. Morphological and functional characteristics of the thyroid gland in diet-induced obesity and its correction in male Wistar rats. Patologicheskaya fiziologiya i eksperimental’naya terapiya [Pathological Physiology and Experimental Therapy], 2023, vol. 67, no. 4, pp. 47–55 (in Russian). https://doi.org/10.25557/0031-2991.2023.04.47-55

25. Kwon O., Kim K. W., Kim M.-S. Leptin signalling pathways in hypothalamic neurons. Cellular and Molecular Life Sciences, 2016, vol. 73, no. 7, pp. 1457–1477. https://doi.org/10.1007/s00018-016-2133-1

26. Shahid M. A., Ashraf M. A., Sharma S. Physiology, Thyroid Hormone. Treasure Island (FL), StatPearls Publ. [Internet], 2025. Available at: https://www.ncbi.nlm.nih.gov/books/NBK500006/ (accessed 10.08.2025).