Zahedan J Res Med Sci. 2019 January; 21(1):e65536. Published online 2019 February 6. doi: 10.5812/zjrms.65536. Research Article Investigating the Effect of Experimental Hypothyroidism on Insulin/Thyroid Hormones and Hepatic Steatosis Vahideh Sadat Nazemi 1 , Mohammad Reza Dayer 1, * and Tayebeh Mohammadi 1, 2 1 Department of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran 2 Department of Basic Sciences, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran * Corresponding author: Department of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran. Tel/Fax: +98-6133331045, Email: mrdayer@scu.ac.ir Received 2017 December 25; Revised 2019 January 13; Accepted 2019 January 26. Abstract Background: The close physiological and biochemical relationships between insulin/thyroid hormones and intermediary metabolism, as well as hepatic homeostasis, are well documented. Apart from significant changes in thyroid hormones levels and altered insulin secretion or resistance, there is no consistency regarding the presence of hepatic storage diseases and fatty liver in hypothyroid patients. Objectives: The main objective of the current study was to evaluate the effect of experimental hypothyroidism on insulin level and histological alterations in the liver such as changes in lipid and glycogen reservoirs. Methods: In this study, 20 adult male Wistar rats were assigned to two similar groups including control and hypothyroid. Experi- mental hypothyroidism was induced by 0.02% propylthiouracil (PTU) administered to rats via drinking water for two months. The rates were then killed and blood samples were assayed for TSH, T4, T3, insulin hormones, and lipid profile. The left lobes of rats’ livers were also used for the histological study. Results: Our results indicated that the two-month administration of 0.02% PTU induced mild hypothyroidism associated with about a 50% reduction in the insulin level. The examination of liver samples showed that there were no significant changes in the overall architecture of liver tissue as compared to normal controls; that is, hepatocytes morphology, appearance, and position of the core, as well as glycogen content, were the same. The main finding of the current work was that in the hypothyroid group, the mild steatosis was accompanied by dyslipidemia. Conclusions: Based on our findings, a two-month administration of 0.02% PTU induces mild hypothyroidism in rates associated with a 50% decrease in the insulin level and mild steatosis in liver hepatocytes. This condition in long period may predispose hy- pothyroid individuals to develop diabetes mellitus and fatty liver simultaneously. Keywords: Propylthiouracil, Mild Hypothyroidism, Fatty Liver, Insulin 1. Background Thyroid hormones, including tetraiodothyronine or thyroxine (T4) and triiodothyronine (T3), play critical roles in intermediary metabolism and energy expendi- ture through affecting carbohydrates, proteins, and lipids metabolism. They may either modulate the metabolic pathway flux directly or modulate the effects of some reg- ulatory hormones on their target cells indirectly (1). For instance, T3 and T4 hormones induce agonistic or antag- onistic effects on insulin levels in different tissues. There- fore, the interactions between insulin and thyroid hor- mones lead to a balance in glucose metabolism in these tissues. Accordingly, any abnormal alterations in thyroid hormones levels in hypo/hyperthyroidism disease distort this balance and lead to impaired glucose metabolism (2). It has been shown that T3 in the liver acts opposite to in- sulin and increases glucose output either by enhancing gluconeogenesis or by accelerating glycogenolysis at the expense of decreasing glycogen content (2, 3). Neverthe- less, there are conflicting reports that T3 acts similar to in- sulin in the expression of glycogen synthase (4, 5). Hypothyroidism is age-dependent and occurs at a higher incidence in women suffering from insufficient production of T3 and T4 hormones in the thyroid gland (6). Thyroid stimulating hormone (TSH) increases highly in this condition to stimulate the thyroid gland for more production of T3 and T4 hormones. High risk of dyslipi- demia and cardiovascular complications are the known consequences in these patients (7). The liver is the place where T4 is deiodinated and converted to T3, wherefore it plays an important role in the metabolic effects of thyroid Copyright © 2019, Zahedan Journal of Research in Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.