Download PDF
Exp Clin Endocrinol Diabetes 2020; 128(06/07): 428-431
DOI: 10.1055/a-1014-2510
Mini-Review

More Than Fever - Novel Concepts in the Regulation of Body Temperature by Thyroid Hormones

Jens Mittag
1   University of Lübeck, Center of Brain Behavior and Metabolism (CBBM), Lübeck, Germany
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Thyroid hormone is well known for its profound effects on body temperature. This minireview summarizes the recent discoveries on the underlying mechanisms, including the role of the hormone’s central actions in the control of brown adipose tissue thermogenesis, its effect on browning of white adipose tissue, the possible involvement of thyroid hormone transporters, and the potential contribution of its downstream metabolites such as 3-iodothyronamine.

Key words

thyroid hormone receptor - brown fat - beige fat - fever - pyrexia - anapyrexia - thyronamine


Publication History

Received: 12 July 2019
Received: 05 September 2019

Accepted: 16 September 2019

Article published online:
25 October 2019

© Georg Thieme Verlag KG
Stuttgart · New York

 

  • References

  • 1 Silva JE. Thermogenic mechanisms and their hormonal regulation. Physiological Reviews 2006; 86: 435-464
    CrossrefPubMedGoogle Scholar
  • 2 Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiological Reviews 2004; 84: 277-359
    CrossrefPubMedGoogle Scholar
  • 3 Wikstrom L, Johansson C, Salto C. et al. Abnormal heart rate and body temperature in mice lacking thyroid hormone receptor alpha 1. The EMBO Journal 1998; 17: 455-461
    CrossrefPubMedGoogle Scholar
  • 4 Yen PM. Physiological and molecular basis of thyroid hormone action. Physiological Reviews 2001; 81: 1097-1142
    CrossrefPubMedGoogle Scholar
  • 5 Mittag J. Peripheral Regulation of Energy Metabolism by Thyroid Hormone. Hot Thyroidology 2009; HT02/09
    PubMedGoogle Scholar
  • 6 Bianco AC, McAninch EA. The role of thyroid hormone and brown adipose tissue in energy homoeostasis. The Lancet Diabetes & Endocrinology 2013; 1: 250-258 DOI: 10.1016/S2213-8587(13)70069-X.
    CrossrefPubMedGoogle Scholar
  • 7 Hoefig CS, Harder L, Oelkrug R. et al. Thermoregulatory and cardiovascular consequences of a transient thyrotoxicosis and recovery in male mice. Endocrinology 2016; 157: 2957-2967 DOI: 10.1210/en.2016-1095.
    CrossrefPubMedGoogle Scholar
  • 8 Johann K, Cremer AL, Fischer AW. et al. Thyroid-hormone-induced browning of white adipose tissue does not contribute to thermogenesis and glucose consumption. Cell Reports 2019; 27: 3385-3400 e3383 DOI: 10.1016/j.celrep.2019.05.054.
    CrossrefPubMedGoogle Scholar
  • 9 Warner A, Rahman A, Solsjö P. et al. Inappropriate heat dissipation ignites brown fat thermogenesis in mice with a mutant thyroid hormone receptor alpha 1. Proceedings of the National Academy of Sciences of the United States of America 2013; 110: 16241-16246
    CrossrefPubMedGoogle Scholar
  • 10 Lopez M, Varela L, Vazquez MJ. et al. Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. Nature Medicine 2010; 16: 1001-1008
    CrossrefPubMedGoogle Scholar
  • 11 Martinez-Sanchez N, Seoane-Collazo P, Contreras C. et al. Hypothalamic AMPK-ER Stress-JNK1 axis mediates the central actions of thyroid hormones on energy balance. Cell Metabolism 2017; 26: 212-229 e212 DOI: 10.1016/j.cmet.2017.06.014.
    CrossrefPubMedGoogle Scholar
  • 12 Weiner J, Hankir M, Heiker JT. et al. Thyroid hormones and browning of adipose tissue. Molecular and Cellular Endocrinology 2017; 458: 156-159 DOI: 10.1016/j.mce.2017.01.011.
    CrossrefPubMedGoogle Scholar
  • 13 Martinez-Sanchez N, Moreno-Navarrete JM, Contreras C. et al. Thyroid hormones induce browning of white fat. The Journal of Endocrinology 2017; 232: 351-362 DOI: 10.1530/JOE-16-0425.
    CrossrefPubMedGoogle Scholar
  • 14 Warner A, Mittag J. Breaking BAT: can browning create a better white?. The Journal of Endocrinology 2016; 228: R19-R29 DOI: 10.1530/JOE-15-0408.
    CrossrefPubMedGoogle Scholar
  • 15 Lin JZ, Martagon AJ, Cimini SL. et al. Pharmacological activation of thyroid hormone receptors elicits a functional conversion of white to brown fat. Cell Reports 2015; 13: 1528-1537 DOI: 10.1016/j.celrep.2015.10.022.
    CrossrefPubMedGoogle Scholar
  • 16 Dittner C, Lindsund E, Cannon B. et al. At thermoneutrality, acute thyroxine-induced thermogenesis and pyrexia are independent of UCP1. Molecular Metabolism 2019; 25: 20-34 DOI: 10.1016/j.molmet.2019.05.005.
    CrossrefPubMedGoogle Scholar
  • 17 Little AG, Seebacher F. The evolution of endothermy is explained by thyroid hormone-mediated responses to cold in early vertebrates. The Journal of Experimental Biology 2014; 217: 1642-1648 DOI: 10.1242/jeb.088880.
    CrossrefPubMedGoogle Scholar
  • 18 Gavrila A, Hasselgren PO, Glasgow A. et al. Variable cold-induced brown adipose tissue response to thyroid hormone status. Thyroid 2017; 27: 1-10 DOI: 10.1089/thy.2015.0646.
    CrossrefPubMedGoogle Scholar
  • 19 Klieverik LP, Coomans CP, Endert E. et al. Thyroid hormone effects on whole-body energy homeostasis and tissue-specific fatty acid uptake in vivo. Endocrinology 2009; 150: 5639-5648 DOI: 10.1210/en.2009-0297.
    CrossrefPubMedGoogle Scholar
  • 20 Friesema EC, Jansen J, Milici C. et al. Thyroid hormone transporters. Vitamins and Hormones 2005; 70: 137-167
    CrossrefPubMedGoogle Scholar
  • 21 de Jesus LA, Carvalho SD, Ribeiro MO. et al. The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. The Journal of Clinical Investigation 2001; 108: 1379-1385
    CrossrefPubMedGoogle Scholar
  • 22 Schwartz CE, Stevenson RE. The MCT8 thyroid hormone transporter and Allan-Herndon-Dudley syndrome. Best Practice & Research Clinical Endocrinology & Metabolism 2007; 21: 307-321 DOI: 10.1016/j.beem.2007.03.009.
    CrossrefPubMedGoogle Scholar
  • 23 Di Cosmo C, Liao XH, Ye H. et al. Mct8-deficient mice have increased energy expenditure and reduced fat mass that is abrogated by normalization of serum T3 levels. Endocrinology 2013; 154: 4885-4895 DOI: 10.1210/en.2013-1150.
    CrossrefPubMedGoogle Scholar
  • 24 Mayerl S, Muller J, Bauer R. et al. Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. The Journal of Clinical Investigation 2014; 124: 1987-1999 DOI: 10.1172/JCI70324.
    CrossrefPubMedGoogle Scholar
  • 25 Trajkovic M, Visser TJ, Mittag J. et al. Abnormal thyroid hormone metabolism in mice lacking the monocarboxylate transporter 8. The Journal of Clinical Investigation 2007; 117: 627-635
    CrossrefPubMedGoogle Scholar
  • 26 Stromme P, Groeneweg S, Lima de Souza EC. et al. Mutated thyroid hormone transporter OATP1C1 associates with severe brain hypometabolism and juvenile neurodegeneration. Thyroid 2018; 28: 1406-1415 DOI: 10.1089/thy.2018.0595.
    CrossrefPubMedGoogle Scholar
  • 27 Mayerl S, Schmidt M, Doycheva D. et al. Thyroid hormone transporters MCT8 and OATP1C1 control skeletal muscle regeneration. Stem Cell Reports 2018; 10: 1959-1974 DOI: 10.1016/j.stemcr.2018.03.021.
    CrossrefPubMedGoogle Scholar
  • 28 Hoefig CS, Kohrle J, Brabant G. et al. Evidence for extrathyroidal formation of 3-iodothyronamine in humans as provided by a novel monoclonal antibody-based chemiluminescent serum immunoassay. The Journal of Clinical Endocrinology and Metabolism 2011; 96: 1864-1872 DOI: 10.1210/jc.2010-2680.
    CrossrefPubMedGoogle Scholar
  • 29 Kohrle J. The colorful diversity of thyroid hormone metabolites. European Thyroid Journal 2019; 8: 115-129 DOI: 10.1159/000497141.
    CrossrefPubMedGoogle Scholar
  • 30 Scanlan TS, Suchland KL, Hart ME. et al. 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nature Medicine 2004; 10: 638-642
    CrossrefPubMedGoogle Scholar
  • 31 Gachkar S, Oelkrug R, Martinez-Sanchez N. et al. 3-Iodothyronamine induces tail vasodilation through central action in male mice. Endocrinology 2017; 158: 1977-1984 DOI: 10.1210/en.2016-1951.
    CrossrefPubMedGoogle Scholar
  • 32 Braunig J, Mergler S, Jyrch S. et al. 3-Iodothyronamine activates a set of membrane proteins in murine hypothalamic cell lines. Frontiers in Endocrinology 2018; 9: 523 DOI: 10.3389/fendo.2018.00523.
    CrossrefPubMedGoogle Scholar
  • 33 Harder L, Schanze N, Sarsenbayeva A. et al. In vivo effects of repeated thyronamine administration in male C57BL/6J mice. European Thyroid Journal 2018; 7: 3-12 DOI: 10.1159/000481856.
    CrossrefPubMedGoogle Scholar
  • 34 Hoefig CS, Jacobi SF, Warner A. et al. 3-Iodothyroacetic acid lacks thermoregulatory and cardiovascular effects in vivo. British Journal of Pharmacology 2015; 172: 3426-3433 DOI: 10.1111/bph.13131.
    CrossrefPubMedGoogle Scholar
  • 35 Magnus-Levy A. Uber den respiratorischen Gaswechsel unter dem Einfluss der Thyroidea sowie unter verschiedenen pathologischen Zustanden. Berlin Klin Wochenschr 1895; 34: 650-652
    PubMedGoogle Scholar