Glucocorticoids and regulation of brown adipose tissue in humans – physiological and pathophysiological considerations

Authors

  • Aleksander Rajczewski Poznan University of Medical Sciences
  • Magdalena Gibas-Dorna Poznan University of Medical Sciences, Department of Physiology

DOI:

https://doi.org/10.20883/jms.2017.236

Keywords:

brown adipose tissue, glucocorticoids, obesity, WAT browning

Abstract

This review discusses the effects of glucocorticoids (GCs) on brown adipose tissue (BAT) in the context of obesity prevention and therapy. Due to the unique expression of the uncoupling protein 1 (UCP1), BAT is capable of non-shivering thermogenesis, also defined as a metabolic heat production, related to increased metabolic rate. All processes that contribute to an increase in activity and/or quantity of BAT are able to upturn metabolism, and thus enable the above therapeutic goals to be achieved. GCs may stimulate BAT differentiation and proliferation. In the case of differentiation, the opposite effect of GCs has been also described. Within white adipose tissue (WAT) GCs inhibit the formation of so called beige adipocytes that are functionally and morphologically similar to the adipocytes from BAT. The activity of GCs with concomitant inhibition of WAT browning is mediated by the induction of microRNA-27b (MIR27B) expression. GCs are responsible for the decline in BAT activity as the body ages. Depriving the body of an enzyme responsible for local reduction of cortisone into an active GC-cortisol in BAT (11ß-hydroxysteroid dehydrogenase type 1; 11ß-HSD1) prevents the reduction of BAT activity. The effects of high doses of GCs on BAT generally depend on the exposure time. Prolonged elevation in GCs level decreases BAT activity. During adrenergic stimulation the effect of GCs on BAT is ambiguous, because both decrease and increase in activity has been described. A full understanding of the GCs impact on brown remodeling in WAT may reveal a discovery of a novel preventive and therapeutic strategies for obesity and possibly other metabolic disorders.

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References

Ravussin E, Kozak LP. Have we entered the brown adipose tissue renaissance? Obes Rev. 2009 May;10(3):265–8.

UCP1 uncoupling protein 1 [Homo sapiens (human)] – Gene – NCBI. [Internet] [Cited 2017 Apr 9]. Available at: https://www.ncbi.nlm.nih.gov/gene/7350.

Barclay JL, Agada H, Jang C, Ward M, Wetzig N, Ho KKY. Effects of glucocorticoids on human brown adipocytes. J Endocrinol. 2015 Feb;224(2):139–47.

Singh S, Rajput YS, Barui AK, Sharma R, Grover S. Expression of developmental genes in brown fat cells grown in vitro is linked with lipid accumulation. In Vitro Cell Dev Biol Anim. 2015 Nov;51(10):1003–11.

Hudak CS, Sul HS. Pref-1, a Gatekeeper of Adipogenesis. Front Endocrinol (Lausanne) [Internet]. 2013 Jul 3 [Cited 2017 Apr 9]. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699714.

Armengol J, Villena JA, Hondares E, Carmona MC, Sul HS, Iglesias R, et al. Pref-1 in brown adipose tissue: specific involvement in brown adipocyte differentiation and regulatory role of C/EBP?. Biochem J. 2012 May 1;443(3):799–810.

Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nat Med. 2013 Oct;19(10):1252–63.

van den Beukel JC, Boon MR, Steenbergen J, Rensen PCN, Meijer OC, Themmen APN, et al. Cold Exposure Partially Corrects Disturbances in Lipid Metabolism in a Male Mouse Model of Glucocorticoid Excess. Endocrinology. 2015 Nov;156(11):4115–28.

Kong X, Yu J, Bi J, Qi H, Di W, Wu L, et al. Glucocorticoids transcriptionally regulate miR-27b expression promoting body fat accumulation via suppressing the browning of white adipose tissue. Diabetes. 2015 Feb;64(2):393–404.

Seale P, Kajimura S, Yang W, Chin S, Rohas LM, Uldry M, et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab. 2007 Jul;6(1):38–54.

Lee M-J, Pramyothin P, Karastergiou K, Fried SK. Deconstructing the roles of glucocorticoids in adipose tissue biology and the development of central obesity. Biochim Biophys Acta. 2014 Mar;1842(3):473–81.

Doig CL, Fletcher RS, Morgan SA, McCabe EL, Larner DP, Tomlinson JW, et al. 11ß-HSD1 modulates the set-point of brown adipose tissue response to glucocorticoids in male mice. Endocrinology. 2017 Mar 27.

Poggioli R, Ueta CB, Drigo RAE, Castillo M, Fonseca TL, Bianco AC. Dexamethasone reduces energy expenditure and increases susceptibility to diet-induced obesity in mice. Obesity (Silver Spring). 2013 Sep;21(9):E415–420.

Zeng X, Jedrychowski MP, Chen Y, Serag S, Lavery GG, Gygi SP, et al. Lysine-specific demethylase 1 promotes brown adipose tissue thermogenesis via repressing glucocorticoid activation. Genes Dev. 2016 Aug 15;30(16):1822–36.

Alvarez-Crespo M, Csikasz RI, Martínez-Sánchez N, Diéguez C, Cannon B, Nedergaard J, et al. Essential role of UCP1 modulating the central effects of thyroid hormones on energy balance. Mol Metab. 2016 Feb 10;5(4):271–82.

Bianco AC, Silva JE. Intracellular conversion of thyroxine to triiodothyronine is required for the optimal thermogenic function of brown adipose tissue. J Clin Invest. 1987. Jan;79(1):295–300.

Martinez-deMena R, Calvo R-M, Garcia L, Obregon MJ. Effect of glucocorticoids on the activity, expression and proximal promoter of type II deiodinase in rat brown adipocytes. Mol Cell Endocrinol. 2016 Jun 15;428:58–67.

Sotelo-Rivera I, Jaimes-Hoy L, Cote-Vélez A, Espinoza-Ayala C, Charli J-L, Joseph-Bravo P. An acute injection of corticosterone increases thyrotrophin-releasing hormone expression in the paraventricular nucleus of the hypothalamus but interferes with the rapid hypothalamus pituitary thyroid axis response to cold in male rats. J Neuroendocrinol. 2014 Dec;26(12):861–9.

Ramage LE, Akyol M, Fletcher AM, Forsythe J, Nixon M, Carter RN, et al. Glucocorticoids Acutely Increase Brown Adipose Tissue Activity in Humans, Revealing Species-Specific Differences in UCP-1 Regulation. Cell Metab. 2016 Jul 12;24(1):130–41.

Virtue S, Vidal-Puig A. Assessment of brown adipose tissue function. Front Physiol [Internet]. 2013 Jun 4 [cited 2017 May 3]. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671177.

Yoneshiro T, Aita S, Matsushita M, Okamatsu-Ogura Y, Kameya T, Kawai Y, et al. Age-Related Decrease in Cold-Activated Brown Adipose Tissue and Accumulation of Body Fat in Healthy Humans. Obesity. 2011 Sep 1;19(9):1755–60.

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Published

2017-09-30

How to Cite

1.
Rajczewski A, Gibas-Dorna M. Glucocorticoids and regulation of brown adipose tissue in humans – physiological and pathophysiological considerations. JMS [Internet]. 2017 Sep. 30 [cited 2024 Apr. 20];86(3):227-30. Available from: https://jms.ump.edu.pl/index.php/JMS/article/view/236

Issue

Section

Review Papers
Received 2017-06-05
Accepted 2017-06-27
Published 2017-09-30