Abstract

The purpose of our study was to observe adipokine expression and endothelial function in subclinical hypothyroidism (sHT) rats and to determine whether levothyroxine (LT4) treatment affects these changes. Sixty-five male Wistar rats were randomly divided into five groups: the control group; sHT A, B and C groups and the sHT + T4 group. The sHT rats were induced by methimazole (MMI) and the sHT + T4 rats were administered LT4 treatment after 8 weeks of MMI administration. Thyroid function and lipid levels were measured using radioimmunoassays and enzymatic colorimetric methods, respectively. Serum adiponectin (APN), chemerin, TNF-α, endothelin (ET-1) and nitric oxide (NO) levels were measured using ELISA kits and a nitric-reductive assay. The expression of APN, chemerin and TNF-α in visceral adipose tissue (VAT) was measured in experimental rats using RT-PCR and Western blotting. Hematoxylin–eosin (HE) staining was used to observe changes in adipose tissue. The sHT rats had significantly higher levels of thyroid-stimulating hormone (TSH), TNF-α, chemerin, ET-1, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and lower levels of APN and NO than those in control and sHT + T4 rats. Based on Pearson correlation analysis, the levels of chemerin, TNF-α, ET-1, LDL-C, TC and triglyceride (TG) were positively correlated with TSH, but APN and NO levels were negatively correlated with TSH. These findings demonstrated that high TSH levels contribute to the changes of adipokines and endothelial dysfunction in sHT, but LT4 treatment ameliorates those changes.

Highlights

  • Subclinical hypothyroidism is defined by increased thyroid-stimulating hormone (TSH) with normal thyroid hormone concentrations

  • The Subclinical hypothyroidism (sHT) rats displayed significantly decreased serum nitric oxide (NO) levels and an increased serum ET-1 levels compared with the levels observed in control rats (P < 0.05)

  • The results showed that the level of TSH was significantly positively correlated with levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), TG, chemerin, TNF-α and ET-1 (P < 0.01), but significantly negatively correlated with levels of APN and NO (P < 0.01)

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Summary

Introduction

Subclinical hypothyroidism (sHT) is defined by increased thyroid-stimulating hormone (TSH) with normal thyroid hormone concentrations. A relationship between sHT and atherosclerosis (AS) was reported in a large populationbased study [2, 3]. Multiple lines of evidence have shown that adipokines [4], endothelial dysfunction [5] and dyslipidemia [6] play a central role in the development of AS, but the relationship between these markers and TSH levels in the context of sHT is still unclear. Visceral adipose tissue (VAT) is the main adipose tissue that produces diverse adipokines, and VAT volume is increased in patients with sHT compared with VAT volume in normal controls [8]. The morphological changes of adipocytes in sHT have not been studied

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