Thyroid morphology and functional alterations in male and female rats with diet-induced visceral obesity

Abstract

With obesity reaching epidemic proportions worldwide, its impact on thyroid function is gaining increasing attention. Epidemiological studies show an association between obesity, hypothyroidism, and circulating thyroid antibodies but experimental research is needed to investigate the mechanisms underlying these associations. This study aimed to investigate thyroid function indicators in male and female rats subjected to a high-calorie diet for 16 weeks. We assessed mass-metric indices, blood biochemical markers, thyroid morphometry, and tissue concentrations of triglycerides, malonic dialdehyde (MDA), and thyroperoxidase (TPO) activity. The results revealed biochemical features of metabolic syndrome, including elevated thyroxine (T4) levels in peripheral blood. Morphological analysis indicated steatosis and thyroid hypofunction, with increased triglyceride accumulation, decreased TPO activity, and lower MDA levels in the thyroid tissue. These findings suggest that visceral obesity in male and female rats promotes early signs of thyroid dysfunction, potentially leading to hypothyroidism.

Keywords

High-calorie diet / Visceral obesity / Rats / Thyroid function / Thyroid hormones / Morphological changes

Funding

This work was supported by the State Program for Scientific Research of the National Academy of Sciences of Belarus (No.: 4.1.1.5).

Conflict of interest

The authors declare that they have no competing interests.

References

[1] Okunogbe A, Nugent R, Spencer G, Powis J, Ralston J, Wilding J. Economic impacts of overweight and obesity: Current and future estimates for 161 countries. BMJ Glob Health. 2022; 7(9):e009773. doi: 10.1136/bmjgh-2022-009773

[2] Reinehr T. Obesity and thyroid function. Mol Cell Endocrinol. 2010; 316(2):165-171. doi: 10.1016/j.mce.2009.06.005

[3] Sanyal D, Raychaudhuri M. Hypothyroidism and obesity: An intriguing link. Indian J Endocrinol Metab. 2016; 20(4):554-557. doi: 10.4103/2230-8210.183454

[4] Du FM, Kuang HY, Duan BH, Liu DN, Yu XY. Associations between thyroid hormones within the euthyroid range and indices of obesity in obese Chinese women of reproductive age. Metab Syndr Relat Disord. 2019; 17(8):416-422. doi: 10.1089/met.2019.0036

[5] Alevizaki M, Saltiki K, Voidonikola P, Mantzou E, Papamichael C, Stamatelopoulos K. Free thyroxine is an independent predictor of subcutaneous fat in euthyroid individuals. Eur J Endocrinol. 2009; 161(3):459-465. doi: 10.1530/EJE-09-0441

[6] Song RH, Wang B, Yao QM, Li Q, Jia X, Zhang JA. The impact of obesity on thyroid autoimmunity and dysfunction: A systematic review and meta-analysis. Front Immunol. 2019; 10:2349. doi: 10.3389/fimmu.2019.02349

[7] Yan Y, Xu M, Wu M, et al. Obesity is associated with subclinical hypothyroidism in the presence of thyroid autoantibodies: A cross-sectional study. BMC Endocr Disord. 2022; 22(1):94. doi: 10.1186/s12902-022-00981-0

[8] Gancheva S, Zhelyazkova-Savova M, Galunska B, Chervenkov T. Experimental models of metabolic syndrome in rats. Scr Sci Med. 2015; 47(2):14-21. doi: 10.14748/ssm.v47i2.1145

[9] Marcondes FK, Bianchi FJ, Tanno AP. Determination of the estrous cycle phases of rats: Some helpful considerations. Braz J Biol. 2002; 62(4A):609-614. doi: 10.1590/s1519-69842002000400008

[10] Khoubnasabjafari M, Ansarin K, Jouyban A. Reliability of malondialdehyde as a biomarker of oxidative stress in psychological disorders. Bioimpacts. 2015; 5(3):123-127. doi: 10.15171/bi.2015.20

[11] Alexander NM. A spectrophotometric assay for iodide oxidation by thyroid peroxidase. Anal Biochem. 1962; 4: 341-345. doi: 10.1016/0003-2697(62)90097-0

[12] Митюкова ТА, Чудиловская ЕН, Мигалевич АС. Определение активности тиреопероксидазы в ткани щитовидной железы (экспериментальное исследование). Лабораторная диагностика. Восточная Европа. (Mityukova TA, Chudilovskaya EH, Mihalevich AC. Determination of thyroid peroxidase activity in the thyroid tissue of rats [experimental study]. Laboratory diagnostics. East Eur). 2020;9(3):285-293. [In Russ]. doi: 10.34883/PI.2020.9.3.009

[13] Басалай АА, Кузнецова ТЕ, Митюкова ТА, и др. Морфофункциональное состояние печени крыс-самцов линии Вистар при диет-индуцированном ожирении и его коррекции. Известия Национальной Академии Наук Беларуси. Серия Медицинских Наук. (Basalai AA, Kuznetsova TE, Mityukova TA, et al. Morphofunctional state of the liver of male Wistar rats during diet-induced obesity and its correction. Proc Natl Acad Sci Belarus Med Ser). 2022;19(3):308-320. [In Russ]. doi: 10.29235/1814-6023-2022-19-3-308-320

[14] Shao SS, Zhao YF, Song YF, et al. Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats. Acta Pharmacol Sin. 2014; 35(11):1411-1420. doi: 10.1038/aps.2014.82

[15] Lee MH, Lee JU, Joung KH, et al. Thyroid dysfunction associated with follicular cell steatosis in obese male mice and humans. Endocrinology. 2015; 156(3):1181-1193. doi: 10.1210/en.2014-1670

[16] Митюкова ТА, Кузнецова ТЕ, Басалай АА, и др. Морфологические и функциональные характеристики щитовидной железы при диет-индуцированном ожирении и его коррекции у крыс самцов Вистар. Патологическая Физиология и Экспериментальная Терапия. (Mityukova TA, Kuznetsova TE, Basalai AA, et al. Morphological and functional characteristics of the thyroid gland in diet-induced obesity and its correction in male Wistar rats. Pathol Physiol Exp Ther). 2023;67(4):47-55. [In Russ]. doi: 10.25557/0031-2991.2023.04.47-55

[17] Kistner TM, Pedersen BK, Lieberman DE. Interleukin 6 as an energy allocator in muscle tissue. Nat Metab. 2022; 4(2): 170-179. doi: 10.1038/s42255-022-00538-4

[18] Mityukova TA, Basalai AA, Chudilovskaya KN, Poluliakh OE, Shcherbakov YV, Kastiuchenka MS. Decrease in muscle mass in diet-induced visceral obesity in male wistar rats: Relationship with hormonal and metabolic parameters. J Evol Biochem Physiol. 2023; 59(4):1277-1286. doi: 10.1134/S0022093023040208

[19] Carvalho DP, Dupuy C. Thyroid hormone biosynthesis and release. Mol Cell Endocrinol. 2017; 458:6-15. doi: 10.1016/j.mce.2017.01.038

[20] Szanto I, Pusztaszeri M, Mavromati M. H2O2 metabolism in normal thyroid cells and in thyroid tumorigenesis: Focus on NADPH oxidases. Antioxidants (Basel). 2019; 8(5):126. doi: 10.3390/antiox8050126

[21] Митюкова ТА, Чудиловская ЕН, Басалай АА. Активность 5’-дейодиназы йодотиронина I типа в печени у крыс получающих высококалорийную диету (экспериментальное исследование). Лабораторная диагностика. Восточная Европа. (Mityukova TA, Chudilovskaya EH, Basalai AA. Activity of type I iodothyronine 5’-deiodinase in the liver in rats receiving a high-calorie diet [experimental study]. laboratory diagnostics. East Eur). 2022;11(1):60-68. [In Russ]. doi: 10.34883/PI.2022.11.1.016

[22] Gereben B, Zeöld A, Dentice M, Salvatore D, Bianco AC. Activation and inactivation of thyroid hormone by deiodinases: Local action with general consequences. Cell Mol Life Sci. 2008; 65(4):570-590. doi: 10.1007/s00018-007-7396-0

[23] Chawla S, Jena S. The anatomy and physiology of laboratory rat. In: Essentials of Laboratory Animal Science: Principles and Practices. Vol. 1. Singapore: Springer; 2021. p. 187-209. doi: 10.1007/978-981-16-0987-9_9

[24] Rizk FH, Barhoma RAE, El-Saka MH, et al. Exercise training and spexin ameliorate thyroid changes in obese type 2 diabetic rats: The possible interlaying mechanisms. Am J Physiol Endocrinol Metab. 2024; 327(3):E313-E327. doi: 10.1152/ajpendo.00213.2024

[25] Biondi B, Kahaly GJ, Robertson RP. Thyroid dysfunction and diabetes mellitus: Two closely associated disorders. Endocr Rev. 2019; 40(3):789-824. doi: 10.1210/er.2018-00163

[26] Mohammed Hussein SM, AbdElmageed RM. The relationship between type 2 diabetes mellitus and related thyroid diseases. Cureus. 2021; 13(12):e20697. doi: 10.7759/cureus.20697

[27] Butler PW, Smith SM, Linderman JD, et al. The Thr92Ala 5’ type 2 deiodinase gene polymorphism is associated with a delayed triiodothyronine secretion in response to the thyrotropin-releasing hormone-stimulation test: A pharmacogenomic study. Thyroid. 2010;20(12): 1407-1412. doi: 10.1089/thy.2010.0244

[28] Shpakov AO. Molecular mechanisms of the relationship between thyroid dysfunctions and diabetes mellitus. J Evol Biochem Physiol. 2018; 54:257-266. doi: 10.1134/S0022093018040014