Hypothyroidism Induces a Moderate Steatohepatitis Accompanied by Liver Regeneration, Mast Cells Infiltration, and Changes in the Expression of the Farnesoid X Receptor

Rodríguez-Castelán, Julia; Corona-Pérez, Adriana; Nicolás-Toledo, Leticia; Martı́nez–Gómez, Margarita; Castelán, Francisco; Cuevas-Romero, Estela

doi:10.1055/s-0042-112367

Cited by 15 publications

(13 citation statements)

References 45 publications

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“…There are miscellaneous reports in conformity with our findings, which show lipid depositions in drug-induced hypothyroid models (22,23), whereas there are also some in contrast (24,25). Our histological studies indicated the accumulation of glycogen depositions in the liver of the hypothyroid group as suggested by others (26).…”

Section: Discussionsupporting

confidence: 92%

Investigating the Effect of Experimental Hypothyroidism on Insulin/Thyroid Hormones and Hepatic Steatosis

Nazemi

Dayer

Mohammadi

2019

Zahedan J Res Med Sci

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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. Experimental 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 hypothyroid individuals to develop diabetes mellitus and fatty liver simultaneously.

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Section: Discussionsupporting

confidence: 92%

Investigating the Effect of Experimental Hypothyroidism on Insulin/Thyroid Hormones and Hepatic Steatosis

Nazemi

Dayer

Mohammadi

2019

Zahedan J Res Med Sci

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“…In this regard, adipocytes from the VAT of diverse mammals express TRs and deiodinases, suggesting a direct effect of thyroid hormones on this tissue [48]. Additionally, dyslipidemias and hypertrophy of the periovarian VAT found in hypothyroid virgin rabbits seems to be accompanied by steatohepatitis [49]. This conjunction of results could help to explain the link between ovarian dysfunction and nonalcoholic fatty liver disease, obesity, insulin resistance, and dyslipidemias observed in women [50].…”

Section: Discussionmentioning

confidence: 99%

Hypothyroidism Reduces the Size of Ovarian Follicles and Promotes Hypertrophy of Periovarian Fat with Infiltration of Macrophages in Adult Rabbits

Rodríguez-Castelán

Méndez-Tepepa

Carrillo-Portillo

et al. 2017

BioMed Research International

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Ovarian failure is related to dyslipidemias and inflammation, as well as to hypertrophy and dysfunction of the visceral adipose tissue (VAT). Although hypothyroidism has been associated with obesity, dyslipidemias, and inflammation in humans and animals, its influence on the characteristics of ovarian follicles in adulthood is scarcely known. Control and hypothyroid rabbits were used to analyze the ovarian follicles, expression of aromatase in the ovary, serum concentration of lipids, leptin, and uric acid, size of adipocytes, and infiltration of macrophages in the periovarian VAT. Hypothyroidism did not affect the percentage of functional or atretic follicles. However, it reduced the size of primary, secondary, and tertiary follicles considered as large and the expression of aromatase in the ovary. This effect was associated with high serum concentrations of total cholesterol and low-density lipoprotein cholesterol (LDL-C). In addition, hypothyroidism induced hypertrophy of adipocytes and a major infiltration of CD68+ macrophages into the periovarian VAT. Our results suggest that the reduced size of ovarian follicles promoted by hypothyroidism could be associated with dyslipidemias, hypertrophy, and inflammation of the periovarian VAT. Present findings may be useful to understand the influence of hypothyroidism in the ovary function in adulthood.

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“…MB07811 treatment reduced liver steatosis and lowered plasma free fatty acid, triglyceride, and serum AST while upregulating lipid metabolism genes [42]. Finally, similar phenotypes were also noted in rabbits, where hypothyroidism induced moderate NASH [43].…”

Section: Linking Thyroid Hormone and Its Receptors To Chronic Liver Dmentioning

confidence: 58%

Thyroid hormone in the regulation of hepatocellular carcinoma and its microenvironment

et al. 2018

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Hepatocellular carcinoma (HCC) commonly arises from a liver damaged by extensive inflammation and fibrosis. Various factors including cytokines, morphogens, and growth factors are involved in the crosstalk between HCC cells and the stromal microenvironment. Increasing our understanding of how stromal components interact with HCC and the signaling pathways involved could help identify new therapeutic and/or chemopreventive targets. It has become increasingly clear that the cross-talk between tumor cells and host stroma plays a key role in modulating tumor growth. Emerging reports suggest a relationship between HCC and thyroid hormone signaling (dysfunction), raising the possibility that perturbed thyroid hormone (TH) regulation influences the cancer microenvironment and cancer phenotype. This review provides an overview of the role of thyroid hormone and its related pathways in HCC and, specifically, its role in regulating the tumor microenvironment.

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Hypothyroidism Induces a Moderate Steatohepatitis Accompanied by Liver Regeneration, Mast Cells Infiltration, and Changes in the Expression of the Farnesoid X Receptor

Cited by 15 publications

References 45 publications

Investigating the Effect of Experimental Hypothyroidism on Insulin/Thyroid Hormones and Hepatic Steatosis

Investigating the Effect of Experimental Hypothyroidism on Insulin/Thyroid Hormones and Hepatic Steatosis

Hypothyroidism Reduces the Size of Ovarian Follicles and Promotes Hypertrophy of Periovarian Fat with Infiltration of Macrophages in Adult Rabbits

Thyroid hormone in the regulation of hepatocellular carcinoma and its microenvironment

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