Thyroid Hormones and their Thermogenic Properties
Mélanie DesChâtelets, ND


Brown adipose tissue (BAT)
White adipose tissue (WAT)


Obesity is a major issue in developed countries. Regulating thyroid hormones is a growingly popular adjunct in a comprehensive approach towards weight loss. Despite growing popularity, there is a lack of knowledge about underlying pathways. This review investigates the thermogenic properties of thyroid hormone on brown adipose tissue (BAT), white adipose tissue (WAT) and the hypothalamus. Current evidence about potential inducers of thermogenesis and potential clinical implications for weight loss are explored.



Hulbert AJ. Thyroid hormones and their effects: a new perspective. Biol Rev Camb Philos Soc. 2000; 75:519–631.
Freake HC, Oppenheimer JH. Thermogenesis and thyroid function. Annu Rev Nutr. 1995; 15:263–291.
Mullur R, Liu Y-Y, Brent GA. Thyroid hormone regulation of metabolism. Physiol Rev. 2014; 94:355–382.
Fonseca TL, Werneck-De-Castro JP, Castillo M, et al. Tissue-specific inactivation of type 2 deiodinase reveals multilevel control of fatty acid oxidation by thyroid hormone in the mouse. Diabetes. 2014; 63:1594–1604.
Silva JE. Thermogenic mechanisms and their hormonal regulation. Physiol Rev. 2006; 86:435–464.
Zhang Q, Miao Q, Ye H, et al. The effects of thyroid hormones on brown adipose tissue in humans: a PET-CT study. Diabetes Metab Res Rev. 2014; 30:513–520.
Oelkrug R, Polymeropoulos ET, Jastroch M. Brown adipose tissue: physiological function and evolutionary significance. J Comp Physiol B, Biochem Syst Environ Physiol. 2015;
Gardner DF, Kaplan MM, Stanley CA, Utiger RD. Effect of tri-iodothyronine replacement on the metabolic and pituitary responses to starvation. N Engl J Med. 1979; 300:579–584.
Müller MJ, Bosy-Westphal A. Adaptive thermogenesis with weight loss in humans. Obesity (Silver Spring). 2013; 21:218–228.
Ponrartana S, Hu HH, Gilsanz V. On the relevance of brown adipose tissue in children. Ann NY Acad Sci. 2013; 1302:24–29.
Gilsanz V, Hu HH, Kajimura S. Relevance of brown adipose tissue in infancy and adolescence. Pediatr Res. 2013; 73:3–9.
Cannon B, Nedergaard J. Yes, even human brown fat is on fire! J Clin Invest. 2012; 122:486–489.
Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004; 84:277–359.
Vijgen G, van Marken Lichtenbelt W. Brown adipose tissue: clinical impact of a re-discovered thermogenic organ. Front Biosci (Elite Ed). 2013; 5:823–833.
Cypess AM, Lehman S, Williams G, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009; 360:1509–1517.
Lee J-Y, Takahashi N, Yasubuchi M, et al. Triiodothyronine induces UCP-1 expression and mitochondrial biogenesis in human adipocytes. Am J Physiol, Cell Physiol. 2012; 302:C463–C472.
Stephens M, Ludgate M, Rees DA. Brown fat and obesity: the next big thing? Clin Endocrinol (Oxf). 2011; 74:661–670.
Marrif H, Schifman A, Stepanyan Z, et al. Temperature homeostasis in transgenic mice lacking thyroid hormone receptor-alpha gene products. Endocrinology. 2005; 146:2872–2884.
Martinez-deMena R, Anedda A, Cadenas S, Obregon M-J. TSH effects on thermogenesis in rat brown adipocytes. Mol Cell Endocrinol. 2015; 404:151–158.
Enerbäck S, Jacobsson A, Simpson EM, et al. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature. 1997; 387:90–94.
Ueta CB, Olivares EL, Bianco AC. Responsiveness to thyroid hormone and to ambient temperature underlies differences between brown adipose tissue and skeletal muscle thermogenesis in a mouse model of diet-induced obesity. Endocrinology. 2011; 152:3571–3581.
Stanford KI, Middelbeek RJW, Townsend KL, et al. Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J Clin Invest. 2013; 123:215–223.
Liu X, Zheng Z, Zhu X, et al. Brown adipose tissue transplantation improves whole-body energy metabolism. Cell Res. 2013; 23:851–854.
Liu X, Wang S, You Y, et al. Brown adipose tissue transplantation reverses obesity in Ob/Ob mice. Endocrinology. 2015; 156:2461–2469.
Tsao T-S, Lodish HF, Fruebis J. ACRP30, a new hormone controlling fat and glucose metabolism. Eur J Pharmacol. 2002; 440:213–221.
Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001; 7:941–946.
Kozacz A, Grunt P, Steczkowska M, et al. Thermogenic effect of glucose in hypothyroid subjects. Int J Endocrinol. 2014; 2014:308017.
Kim MS, Hu HH, Aggabao PC, Geffner ME, Gilsanz V . Presence of brown adipose tissue in an adolescent with severe primary hypothyroidism. J Clin Endocrinol Metab. 2014; 99:E1686–E1690.
Silva JE, Larsen PR. Interrelationships among thyroxine, growth hormone, and the sympathetic nervous system in the regulation of 5′-iodothyronine deiodinase in rat brown adipose tissue. J Clin Invest. 1986; 77:1214–1223.
DiSilvestro D, Petrosino J, Aldoori A, Melgar-Bermudez E, Wells A, Ziouzenkova O. Enzymatic intracrine regulation of white adipose tissue. Horm Mol Biol Clin Investig. 2014; 19:39–55.
Wang C-Z, Wei D, Guan M-P, Xue Y-M. Triiodothyronine regulates distribution of thyroid hormone receptors by activating AMP-activated protein kinase in 3T3-L1 adipocytes and induces uncoupling protein-1 expression. Mol Cell Biochem. 2014; 393:247–254.
López M, Alvarez CV, Nogueiras R, Diéguez C. Energy balance regulation by thyroid hormones at central level. Trends Mol Med. 2013; 19:418–427.
Sjögren M, Alkemade A, Mittag J, et al. Hypermetabolism in mice caused by the central action of an unliganded thyroid hormone receptor alpha1. EMBO J. 2007; 26:4535–4545.
Hardie DG. AMPK: positive and negative regulation, and its role in whole-body energy homeostasis. Curr Opin Cell Biol. 2015; 33:1–7.
Hardie DG, Ross FA, Hawley SA. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol. 2012; 13:251–262.
López M, Varela L, Vázquez MJ, et al. Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. Nat Med. 2010; 16:1001–1008.
Coppola A, Liu Z-W, Andrews ZB, et al. A central thermogenic-like mechanism in feeding regulation: an interplay between arcuate nucleus T3 and UCP2. Cell Metab. 2007; 5:21–33.
Grimaldi D, Provini F, Pierangeli G, et al. Evidence of a diurnal thermogenic handicap in obesity. Chronobiol Int. 2015; 32(2):299–302.
al-Adsani H, Hoffer LJ, Silva JE. Resting energy expenditure is sensitive to small dose changes in patients on chronic thyroid hormone replacement. J Clin Endocrinol Metab. 1997; 82:1118–1125.
Martínez de Morentin PB, González-García I, Martins L , et al. Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK. Cell Metab. 2014; 20:41–53.
Zhang Z, Zhang H, Li B, et al. Berberine activates thermogenesis in white and brown adipose tissue. Nat Commun. 2014; 5:5493.
Lee M-S, Kim I-H, Kim C-T, Kim Y. Reduction of body weight by dietary garlic is associated with an increase in uncoupling protein mRNA expression and activation of AMP-activated protein kinase in diet-induced obese mice. J Nutr. 2011; 141:1947–1953.

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