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      Thyroid Stimulating Hormone (TSH) Is Associated With General and Abdominal Obesity: A Cohort Study in School-Aged Girls During Puberty in East China

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          Abstract

          Objectives: Although the association between thyroid stimulating hormone (TSH) and obesity in children has been investigated in several cross-sectional studies, no study evaluated this association among girls during puberty, which were in a key period closely related to the fluctuations of thyroid hormones and development of obesity. Therefore, we conducted a cohort study to investigate the association of general and abdominal obesity with TSH in girls during puberty.

          Setting and participants: A cohort study of 481 school-aged girls during puberty was conducted in four regions in east China, with a baseline survey in 2017 and a follow-up survey in 2019.

          Outcome measures: Anthropometric indexes including height, weight and waist circumference (WC) were measured, and body mass index (BMI) was then calculated. Blood samples were collected to determine TSH and free thyroxine (FT4).

          Results: Of the 474 girls at baseline survey, the prevalences of BMI-based general obesity and WC-based abdominal obesity were 19.8% (94/474) and 21.7% (103/474), respectively. Compared with normal weight girls, the median serum TSH level was significantly higher in general obese girls ( P = 0.037), but not in central obese girls ( P = 0.173). Multiple logistic regression models indicated that those in the highest tertile of serum TSH level had a significantly higher risk of BMI-based overweight/obesity (OR = 1.83, 95% CI 1.01 to 3.32) compared with the lowest tertile. Analyses from 435 girls prospectively followed-up for 2 years revealed that those with general or central obesity also had higher follow-up TSH level ( P = 0.004 and P = 0.008, respectively). The TSH level for girls with general obesity at baseline but normal weight at follow-up was 0.45 mU/L (95% CI 0.11 to 0.79) higher than those with normal weight at baseline and follow-up.

          Conclusions: TSH was positively associated with both general and abdominal obesity among girls during puberty.

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          Most cited references40

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          Adipokines in inflammation and metabolic disease.

          The worldwide epidemic of obesity has brought considerable attention to research aimed at understanding the biology of adipocytes (fat cells) and the events occurring in adipose tissue (fat) and in the bodies of obese individuals. Accumulating evidence indicates that obesity causes chronic low-grade inflammation and that this contributes to systemic metabolic dysfunction that is associated with obesity-linked disorders. Adipose tissue functions as a key endocrine organ by releasing multiple bioactive substances, known as adipose-derived secreted factors or adipokines, that have pro-inflammatory or anti-inflammatory activities. Dysregulated production or secretion of these adipokines owing to adipose tissue dysfunction can contribute to the pathogenesis of obesity-linked complications. In this Review, we focus on the role of adipokines in inflammatory responses and discuss their potential as regulators of metabolic function.
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            Thyroid hormone regulation of metabolism.

            Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, α and β, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T4), to the active form, triiodothyronine (T3), by 5'-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets.
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              Childhood obesity as a predictor of morbidity in adulthood: a systematic review and meta-analysis.

              Obese children are at higher risk of being obese as adults, and adult obesity is associated with an increased risk of morbidity. This systematic review and meta-analysis investigates the ability of childhood body mass index (BMI) to predict obesity-related morbidities in adulthood. Thirty-seven studies were included. High childhood BMI was associated with an increased incidence of adult diabetes (OR 1.70; 95% CI 1.30-2.22), coronary heart disease (CHD) (OR 1.20; 95% CI 1.10-1.31) and a range of cancers, but not stroke or breast cancer. The accuracy of childhood BMI when predicting any adult morbidity was low. Only 31% of future diabetes and 22% of future hypertension and CHD occurred in children aged 12 or over classified as being overweight or obese. Only 20% of all adult cancers occurred in children classified as being overweight or obese. Childhood obesity is associated with moderately increased risks of adult obesity-related morbidity, but the increase in risk is not large enough for childhood BMI to be a good predictor of the incidence of adult morbidities. This is because the majority of adult obesity-related morbidity occurs in adults who were of healthy weight in childhood. Therefore, targeting obesity reduction solely at obese or overweight children may not substantially reduce the overall burden of obesity-related disease in adulthood.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                30 September 2020
                2020
                : 11
                : 620
                Affiliations
                [1] 1Department of Epidemiology, School of Public Health, Fudan University , Shanghai, China
                [2] 2Key Laboratory of Public Health Safety of Ministry of Education , Shanghai, China
                [3] 3Department of Chronic Disease Control and Prevention, Deqing County Center for Disease Control and Prevention , Huzhou, China
                [4] 4Department of Chronic Disease Control and Prevention, Yuhuan City Center for Disease Control and Prevention , Taizhou, China
                [5] 5Department of Chronic Disease Control and Prevention, Minhang District Center for Disease Control and Prevention , Shanghai, China
                [6] 6Department of Chronic Disease Control and Prevention, Haimen City Center for Disease Control and Prevention , Nantong, China
                [7] 7School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa , Ottawa, ON, Canada
                Author notes

                Edited by: Christoph Reiners, University Hospital Würzburg, Germany

                Reviewed by: Takao Ando, Nagasaki University Hospital, Japan; Giorgio Napolitano, University of Studies G. d'Annunzio Chieti and Pescara, Italy

                *Correspondence: Na Wang na.wang@ 123456fudan.edu.cn

                This article was submitted to Thyroid Endocrinology, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2020.00620
                7561409
                33117269
                c9a6afb6-6d37-4596-8e14-e7bcbe7d5394
                Copyright © 2020 Wang, Dong, Fu, Su, Jiang, Xu, Li, Qian, Wang, Chen and Jiang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 17 April 2020
                : 29 July 2020
                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 42, Pages: 9, Words: 5128
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Categories
                Endocrinology
                Original Research

                Endocrinology & Diabetes
                thyroid stimulating hormone,general obesity,central obesity,school-aged girls,puberty,cohort study

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