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      Adipokine expression and endothelial function in subclinical hypothyroidism rats

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          Abstract

          The purpose of our study was to observe adipokine expression and endothelial function in subclinical hypothyroidism (sHT) rats and to determine whether levothyroxine (LT 4) 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 + T 4 group. The sHT rats were induced by methimazole (MMI) and the sHT + T 4 rats were administered LT 4 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 + T 4 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 LT 4 treatment ameliorates those changes.

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          Most cited references46

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          Identification of chemerin receptor (ChemR23) in human endothelial cells: chemerin-induced endothelial angiogenesis.

          Chemerin acting via its distinct G protein-coupled receptor CMKLR1 (ChemR23), is a novel adipokine, circulating levels of which are raised in inflammatory states. Chemerin shows strong correlation with various facets of the metabolic syndrome; these states are associated with an increased incidence of cardiovascular disease (CVD) and dysregulated angiogenesis. We therefore, investigated the regulation of ChemR23 by pro-inflammatory cytokines and assessed the angiogenic potential of chemerin in human endothelial cells (EC). We have demonstrated the novel presence of ChemR23 in human ECs and its significant up-regulation (P<0.001) by pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-6. More importantly, chemerin was potently angiogenic, as assessed by conducting functional in-vitro angiogenic assays; chemerin also dose-dependently induced gelatinolytic (MMP-2 & MMP-9) activity of ECs (P<0.001). Furthermore, chemerin dose-dependently activated PI3K/Akt and MAPKs pathways (P<0.01), key angiogenic and cell survival cascades. Our data provide the first evidence of chemerin-induced endothelial angiogenesis and MMP production and activity. Copyright 2009 Elsevier Inc. All rights reserved.
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            The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial.

            Subclinical hypothyroidism (SCH) is defined as raised serum TSH levels with circulating thyroid hormones within the reference range. It is uncertain whether treatment of SCH with L-thyroxine improves cardiovascular (CV) risk factors and quality of life. The objective of the study was to assess CV risk factors and patient-reported outcomes after treatment. This was a randomized, double-blind, crossover study of L-thyroxine and placebo. The study was conducted with community-dwelling patients. One hundred patients [mean age (sd) 53.8 (12) yr, 81 females] with SCH [mean TSH 6.6 (1.3) mIU/liter] without previously treated thyroid or vascular disease. Intervention consisted of 100 microg L-thyroxine or placebo daily for 12 wk each. Primary parameters were total cholesterol (TC) and endothelial function [brachial artery flow-mediated dilatation (FMD)], an early marker of atherosclerosis. Patient-reported outcomes were also assessed. L-thyroxine treatment reduced TC (vs. placebo) from 231.6 to 220 mg/dl, P < 0.001; low-density lipoprotein cholesterol from 142.9 to 131.3 mg/dl, P < 0.05; waist to hip ratio from 0.83 to 0.81, P < 0.006; and improved FMD from 4.2 to 5.9%, P < 0.001. Multivariate analysis showed that increased serum free T(4) level was the most significant variable predicting reduction in TC or improvement in FMD. Furthermore, the symptom of tiredness improved on L-thyroxine therapy, but other patient-reported outcomes were not significantly different after correction for multiple comparisons. SCH treated by L-thyroxine leads to a significant improvement in CV risk factors and symptoms of tiredness. The CV risk factor reduction is related to the increased level of achieved free T(4) concentration.
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              The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor.

              ACRP30--adipocyte complement-related protein of 30 kDa or AdipoQ--is an abundant serum protein, secreted exclusively from fat cells, which is implicated in energy homeostasis and obesity [1,2]. ACRP30 is a close homologue of the complement protein C1q, which is involved in the recognition of microbial surfaces [3-5] and antibody-antigen complexes [6,7] in the classical pathway of complement. We have determined the crystal structure of a homotrimeric fragment from ACRP30 at 2.1 A resolution. The structure reveals an unexpected homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and C1q families. We suggest that TNFs--which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis--arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between C1q-like proteins and TNFs illuminates the shared functions of these two important groups of proteins.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                February 2018
                12 January 2018
                : 7
                : 2
                : 295-304
                Affiliations
                [1 ]Department of Endocrinology Gansu Provincial Hospital, Lanzhou, China
                [2 ]Department of Clinical Medicine Gansu University of Chinese Medicine, Lanzhou, Gansu, China
                [3 ]Department of Ultrasonic Diagnosis Gansu Provincial Hospital, Lanzhou, China
                Author notes
                Correspondence should be addressed to L Tian: tlm6666@ 123456sina.com

                *(N Gong and C Gao contributed equally to this work)

                Article
                EC180007
                10.1530/EC-18-0007
                5811986
                29440225
                41ec5d86-863f-4b62-afe6-bc59284c83bd
                © 2018 The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 10 January 2018
                : 12 January 2018
                Categories
                Research

                subclinical hypothyroidism,adipose tissue,adipokines,endothelial function,levothyroxine

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