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Metabolites
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Recent Developments in Thyroid Hormone Regulation in Metabolic Diseases
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Recent Developments in Thyroid Hormone Regulation in Metabolic Diseases

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 11297

Special Issue Editors

Prof. Dr. Eleonore Fröhlich

E-Mail Website
Guest Editor
Center for Medical Research, Medical University of Graz, Stiftingtalstraße 24, 8010 Graz, Austria
Interests: physiologically relevant culture models; automated microscopes for cell monitoring; life cell imaging; biological assessment of nano and microparticles
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Richard Wahl

E-Mail Website
Guest Editor
Institute for Clinical Chemistry and Pathobiochemistry, University Hospital Tuebingen, 72076 Tuebingen, Germany
Interests: clinical diagnostic and experimental thyroidology; clinical nuclear chemistry

Special Issue Information

Dear Colleagues,

Today, thyroid diseases have become an interdisciplinary field of general practitioners, internists (endocrinologists, immunologists, oncologists), nuclear medicine specialists including radiation therapists, surgeons, ophthalmologists and other specialties. The use of modern technologies in basic research has enabled more insight into the mode of action of thyroid hormones and their metabolites, resulting in a potential therapeutic use of thyroid hormone metabolites.

One of the main tasks of thyroid hormones is to control important metabolic steps in the organism.  Besides goiters with all their adverse effects on the organism, autoimmune diseases are among the most common thyroid diseases today. Abnormal thyroid hormones in particular have been linked to cardiovascular diseases, metabolic syndrome and cancer. This Special Issue aims to better understand the interplay of metabolic disorders and thyroid hormone metabolism, reveal new mechanisms of action and the regulation of thyroid hormones or their metabolites and identify innovative modalities for the treatment of thyroid diseases. The role of thyroid hormones and their metabolites in metabolic disorders, bile acid signaling, insulin sensitivity, hepatic gluconeogenesis, aging, neuro-modulatory effects and the immune system is still not entirely clear. Further, additional insight is needed into the regulation via the TRH–TSH–thyroid axis by nutritional signals.

We would like to encourage submissions (original articles, reviews, commentaries) on new findings related to normal and dysregulated thyroid metabolism.  

Prof. Dr. Eleonore Fröhlich
Prof. Dr. Richard Wahl
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • T3, T4, TRH and TSH
  • PPAR, liver X receptor
  • bile acid
  • insulin, insulin resistance, gluconeogenesis
  • brown fat, white fat
  • leptin, ghrelin
  • inflammatory markers
  • epigenetics and molecular biology
  • bone metabolism
  • cardiovascular effects
  • NAFLD/MAFLD

Published Papers (4 papers)

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Research

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24 pages, 3028 KiB  
Article
Changes in Thyroid Metabolites after Liothyronine Administration: A Secondary Analysis of Two Clinical Trials That Incorporated Pharmacokinetic Data
by Nour Diab, Sameer Desale, Mark Danielsen, Josef Köhrle, Nawar Shara and Jacqueline Jonklaas
Metabolites 2022, 12(6), 476; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo12060476 - 24 May 2022
Viewed by 1695
Abstract
We examined relationships between thyroid hormone (TH) metabolites in humans by measuring 3,5-diiodothyronine (3,5-T2) and 3-iodothyronamine (3-T1AM) levels after liothyronine administration. In secondary analyses, we measured 3,5-T2 and 3-T1AM concentrations in stored samples from two clinical trials. In 12 healthy volunteers, THs and [...] Read more.
We examined relationships between thyroid hormone (TH) metabolites in humans by measuring 3,5-diiodothyronine (3,5-T2) and 3-iodothyronamine (3-T1AM) levels after liothyronine administration. In secondary analyses, we measured 3,5-T2 and 3-T1AM concentrations in stored samples from two clinical trials. In 12 healthy volunteers, THs and metabolites were documented for 96 h after a single dose of 50 mcg liothyronine. In 18 patients treated for hypothyroidism, levothyroxine therapy was replaced by daily dosing of 30–45 mcg liothyronine. Analytes were measured prior to the administration of liothyronine weekly for 6 weeks, and then hourly for 8 h after the last liothyronine dose of the study. In the weekly samples from the hypothyroid patients, 3,5-T2 was higher by 0.033 nmol/L with each mcg/dL increase in T4 and 0.24 nmol/L higher with each ng/dL increase in FT4 (p-values = 0.007, 0.0365). In hourly samples after the last study dose of liothyronine, patients with T3 values higher by one ng/dL had 3-T1AM values that were lower by 0.004 nmol/L (p-value = 0.0473); patients with 3,5-T2 higher by one nmol/L had 3-T1AM values higher by 2.45 nmol/L (p-value = 0.0044). The positive correlations between weekly trough levels of 3,5-T2 and T4/FT4 during liothyronine therapy may provide insight into 3,5-T2 production, possibly supporting some production of 3,5-T2 from endogenous T4, but not from exogenous liothyronine. In hourly sampling after liothyronine administration, the negative correlation between T3 levels and 3-T1AM, but positive correlation between 3,5-T2 levels and 3-T1AM could support the hypothesis that 3-T1AM production occurs via 3,5-T2 with negative regulation by T3. Full article
(This article belongs to the Special Issue Recent Developments in Thyroid Hormone Regulation in Metabolic Diseases)
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Review

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13 pages, 1001 KiB  
Review
Hyperthyroidism and Wnt Signaling Pathway: Influence on Bone Remodeling
by Dunja Mudri, Ines Bilić Ćurčić, Lucija Meštrović, Ivica Mihaljević and Tomislav Kizivat
Metabolites 2023, 13(2), 241; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo13020241 - 06 Feb 2023
Cited by 1 | Viewed by 3096
Abstract
Graves’ disease is an autoimmune disease of the thyroid gland, characterized by increased production of thyroid hormones, which can affect many different organ systems in the body. Among other problems, it can cause disorders of the skeletal system, shortening the bone remodeling cycle [...] Read more.
Graves’ disease is an autoimmune disease of the thyroid gland, characterized by increased production of thyroid hormones, which can affect many different organ systems in the body. Among other problems, it can cause disorders of the skeletal system, shortening the bone remodeling cycle and causing a decrease in bone density. The Wnt cascade signaling pathway and the β-catenin, as a part of the canonical Wnt pathway, also play roles in maintaining bone mass. Inhibition of the Wnt pathway can cause bone loss, and its stimulation can increase it. The Wnt signaling pathway influences the effectiveness of thyroid hormones by affecting receptors for thyroid hormones and deiodinase, while thyroid hormones can change levels of β-catenin within the cell cytoplasm. This indicates that the Wnt pathway and thyroid hormone levels, including hyperthyroidism, are linked and may act together to change bone density. In this review article, we attempt to explain the interplay between thyroid hormones and the Wnt pathway on bone density, with a focus on directions for further research and treatment options. Full article
(This article belongs to the Special Issue Recent Developments in Thyroid Hormone Regulation in Metabolic Diseases)
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26 pages, 1580 KiB  
Review
Insight into Potential Interactions of Thyroid Hormones, Sex Hormones and Their Stimulating Hormones in the Development of Non-Alcoholic Fatty Liver Disease
by Eleonore Fröhlich and Richard Wahl
Metabolites 2022, 12(8), 718; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo12080718 - 04 Aug 2022
Cited by 8 | Viewed by 2661
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is a common manifestation of metabolic syndrome. In addition to lifestyle, endocrine hormones play a role in the dysregulation of hepatic metabolism. The most common endocrine hormones contributing to metabolic syndrome are alterations in the levels of thyroid [...] Read more.
Non-Alcoholic Fatty Liver Disease (NAFLD) is a common manifestation of metabolic syndrome. In addition to lifestyle, endocrine hormones play a role in the dysregulation of hepatic metabolism. The most common endocrine hormones contributing to metabolic syndrome are alterations in the levels of thyroid hormones (THs, predominantly in subclinical hypothyroidism) and of sex hormones (in menopause). These hormonal changes influence hepatic lipid and glucose metabolism and may increase hepatic fat accumulation. This review compares the effects of sex hormones, THs and the respective stimulating hormones, Thyroid-Stimulating Hormone (TSH) and Follicle-Stimulating Hormone (FSH), on the development of hepatosteatosis. TSH and FSH may be more relevant to the dysregulation of hepatic metabolism than the peripheral hormones because metabolic changes were identified when only levels of the stimulating hormones were abnormal and the peripheral hormones were still in the reference range. Increased TSH and FSH levels appear to have additive effects on the development of NAFLD and to act independently from each other. Full article
(This article belongs to the Special Issue Recent Developments in Thyroid Hormone Regulation in Metabolic Diseases)
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18 pages, 4949 KiB  
Review
Interplay between Fatty Acid Binding Protein 4, Fetuin-A, Retinol Binding Protein 4 and Thyroid Function in Metabolic Dysregulation
by Daniela Dadej, Ewelina Szczepanek-Parulska and Marek Ruchała
Metabolites 2022, 12(4), 300; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo12040300 - 29 Mar 2022
Cited by 6 | Viewed by 2991
Abstract
Signalling between the tissues integrating synthesis, transformation and utilization of energy substrates and their regulatory hormonal axes play a substantial role in the development of metabolic disorders. Interactions between cytokines, particularly liver derived hepatokines and adipokines, secreted from adipose tissue, constitute one of [...] Read more.
Signalling between the tissues integrating synthesis, transformation and utilization of energy substrates and their regulatory hormonal axes play a substantial role in the development of metabolic disorders. Interactions between cytokines, particularly liver derived hepatokines and adipokines, secreted from adipose tissue, constitute one of major areas of current research devoted to metabolic dysregulation. The thyroid exerts crucial influence on the maintenance of basal metabolic rate, thermogenesis, carbohydrate and lipid metabolism, while its dysfunction promotes the development of metabolic disorders. In this review, we discuss the interplay between three adipokines: fatty acid binding protein type 4, fetuin-A, retinol binding protein type 4 and thyroid hormones, that shed a new light onto mechanisms underlying atherosclerosis, cardiovascular complications, obesity, insulin resistance and diabetes accompanying thyroid dysfunction. Furthermore, we summarize clinical findings on those cytokines in the course of thyroid disorders. Full article
(This article belongs to the Special Issue Recent Developments in Thyroid Hormone Regulation in Metabolic Diseases)
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