Exp Clin Endocrinol Diabetes 2020; 128(06/07): 446-449
DOI: 10.1055/a-1020-5354
Mini-Review

Novel Aspects of White Adipose Tissue Browning by Thyroid Hormones

Kerstin Krause
1   Department of Endocrinology and Nephrology, University Hospital Leipzig, Leipzig, Germany
› Author Affiliations

Abstract

Thyroid hormones are essential for the full thermogenic capacity of brown adipose tissue. The thermogenic response of brown adipocytes to thyroid hormones is resulting from the synergistic interaction of thyroid hormones with the sympathetic nervous system. In recent years, evidence has been provided that thyroid hormones also induce the browning of white adipose tissues. This review will provide a brief overview about the recent findings regarding the effects of thyroid hormones on adipose tissue thermogenesis including central and peripheral regulation of white adipose tissue browning.



Publication History

Received: 14 August 2019

Accepted: 14 August 2019

Article published online:
07 November 2019

© Georg Thieme Verlag KG
Stuttgart · New York

 
  • References

  • 1 Bianco AC, McAninch EA. The role of thyroid hormone and brown adipose tissue in energy homoeostasis. Lancet Diabetes Endocrinol 2013; 1: 250-258
  • 2 Silva JE, Bianco SDC. Thyroid-adrenergic interactions: Physiological and clinical implications. Thyroid Off J Am Thyroid Assoc 2008; 18: 157-165
  • 3 Rubio A, Raasmaja A, Silva JE. Thyroid hormone and norepinephrine signaling in brown adipose tissue. II: Differential effects of thyroid hormone on beta 3-adrenergic receptors in brown and white adipose tissue. Endocrinology 1995; 136: 3277-3284
  • 4 Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell 2014; 156: 20-44
  • 5 Cannon B, Nedergaard J. Brown adipose tissue: Function and physiological significance. Physiol Rev 2004; 84: 277-359
  • 6 Bartness TJ, Vaughan CH, Song CK. Sympathetic and sensory innervation of brown adipose tissue. Int J Obes 2005; 2010 34: S36-S42
  • 7 Rothwell NJ, Stock MJ. A role for brown adipose tissue in diet-induced thermogenesis. Nature 1979; 281: 31-35
  • 8 Petrovic N, Walden TB, Shabalina IG. et al. Chronic peroxisome proliferator-activated receptor γ (PPARγ) Activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem 2010; 285: 7153-7164
  • 9 Harms M, Seale P. Brown and beige fat: Development, function and therapeutic potential. Nat Med 2013; 19: 1252-1263
  • 10 Himms-Hagen J, Cui J, Danforth E. et al. Effect of CL-316,243, a thermogenic beta 3-agonist, on energy balance and brown and white adipose tissues in rats. Am J Physiol 1994; 266: R1371-R1382
  • 11 Cypess AM, Weiner LS, Roberts-Toler C. et al. Activation of human brown adipose tissue by a β3-adrenergic receptor agonist. Cell Metab 2015; 21: 33-38
  • 12 Rohm M, Schäfer M, Laurent V. et al. An AMP-activated protein kinase-stabilizing peptide ameliorates adipose tissue wasting in cancer cachexia in mice. Nat Med 2016; 22: 1120-1130
  • 13 Brent GA. Mechanisms of thyroid hormone action. J Clin Invest 2012; 122: 3035-3043
  • 14 McAninch EA, Bianco AC. Thyroid hormone signaling in energy homeostasis and energy metabolism. Ann NY Acad Sci 2014; 1311: 77-87
  • 15 Ribeiro MO, Carvalho SD, Schultz JJ. et al. Thyroid hormone--sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoform–specific. J Clin Invest 2001; 108: 97-105
  • 16 Salvatore D, Simonides WS, Dentice M. et al. Thyroid hormones and skeletal muscle–new insights and potential implications. Nat Rev Endocrinol 2014; 10: 206-214
  • 17 Silva JE. Fat and energy economy in hypo- and hyperthyroidism are not the mirror image of one another. Endocrinology 2010; 151: 4-6
  • 18 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
  • 19 Martínez-Sánchez 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 Metab 2017; 26: 212-229.e12
  • 20 Cabral A, Valdivia S, Reynaldo M. et al. Short-term cold exposure activates TRH neurons exclusively in the hypothalamic paraventricular nucleus and raphe pallidus. Neurosci Lett 2012; 518: 86-91
  • 21 Nillni EA. Regulation of the hypothalamic thyrotropin releasing hormone (TRH) neuron by neuronal and peripheral inputs. Front Neuroendocrinol 2010; 31: 134-156
  • 22 Miao Y, Warner M, Gustafsson J-Å. Liver X receptor β: New player in the regulatory network of thyroid hormone and ‘browning’ of white fat. Adipocyte 2016; 5: 238-242
  • 23 Weiner J, Kranz M, Klöting N. et al. Thyroid hormone status defines brown adipose tissue activity and browning of white adipose tissues in mice. Sci Rep 2016; 6: 38124
  • 24 Schulz TJ, Huang P, Huang TL. et al. Brown-fat paucity due to impaired BMP signalling induces compensatory browning of white fat. Nature 2013; 495: 379-383
  • 25 Medina-Gomez G, Calvo RM, Obregon M-J. Thermogenic effect of triiodothyroacetic acid at low doses in rat adipose tissue without adverse side effects in the thyroid axis. Am J Physiol - Endocrinol Metab 2008; 294: E688-E697
  • 26 Schueler PA, Schwartz HL, Strait KA. et al. Binding of 3,5,3’-triiodothyronine (T3) and its analogs to the in vitro translational products of c-erbA protooncogenes: differences in the affinity of the alpha- and beta-forms for the acetic acid analog and failure of the human testis and kidney alpha-2 products to bind T3. Mol Endocrinol Baltim Md 1990; 4: 227-234
  • 27 Villicev CM, Freitas FRS, Aoki MS. et al. Thyroid hormone receptor beta-specific agonist GC-1 increases energy expenditure and prevents fat-mass accumulation in rats. J Endocrinol 2007; 193: 21-29
  • 28 Lin JZ, Martagón AJ, Cimini SL. et al. Pharmacological activation of thyroid hormone receptors elicits a functional conversion of white to brown fat. Cell Rep 2015; 13: 1528-1537
  • 29 Finan B, Clemmensen C, Zhu Z. et al. Chemical hybridization of glucagon and thyroid hormone optimizes therapeutic impact for metabolic disease. Cell 2016; 167: 843-857.e14
  • 30 Beaudry JL, Kaur KD, Varin EM. et al. The brown adipose tissue glucagon receptor is functional but not essential for control of energy homeostasis in mice. Mol Metab 2019; 22: 37-48
  • 31 Dicker A, Zhao J, Cannon B. et al. Apparent thermogenic effect of injected glucagon is not due to a direct effect on brown fat cells. Am J Physiol 1998; 275: R1674-R1682
  • 32 Fisher FM, Kleiner S, Douris N. et al. FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis. Genes Dev 2012; 26: 271-281
  • 33 Adams AC, Astapova I, Fisher FM. et al. Thyroid hormone regulates hepatic expression of fibroblast growth factor 21 in a PPARalpha-dependent manner. J Biol Chem 2010; 285: 14078-14082
  • 34 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 Rep 2019; 27: 3385-3400.e3
  • 35 Alvarez-Crespo M, Csikasz RI, Martínez-Sánchez N. et al. Essential role of UCP1 modulating the central effects of thyroid hormones on energy balance. Mol Metab 2016; 5: 271-282
  • 36 Martínez-Sánchez N, Moreno-Navarrete JM, Contreras C. et al. Thyroid hormones induce browning of white fat. J Endocrinol 2017; 232: 351-362
  • 37 Dittner C, Lindsund E, Cannon B. et al. At thermoneutrality, acute thyroxine-induced thermogenesis and pyrexia are independent of UCP1. Mol Metab 2019; 25: 20-34
  • 38 Triandafillou J, Gwilliam C, Himms-Hagen J. Role of thyroid hormone in cold-induced changes in rat brown adipose tissue mitochondria. Can J Biochem 1982; 60: 530-537
  • 39 Sundin U. GDP binding to rat brown fat mitochondria: Effects of thyroxine at different ambient temperatures. Am J Physiol 1981; 241: C134-C139
  • 40 Ramadan W, Marsili A, Larsen PR. et al. Type-2 Iodothyronine 5′Deiodinase (D2) in Skeletal Muscle of C57Bl/6 Mice. II. Evidence for a role of D2 in the hypermetabolism of thyroid hormone receptor α-deficient mice. Endocrinology 2011; 152: 3093-3102