Page 1 of 26
Accepted Preprint first posted on 10 November 2014 as Manuscript JOE-14-0538
JOE-14-0538.R1
The effects of glucocorticoids on human brown adipocytes
1 2
Johanna L Barclay1,4, Hadiya Agada1, Christina Jang1,2, Micheal Ward3, Neil Wetzig2, Ken KY Ho1,2,4
3 4
1
School of Medicine, University of Queensland, Herston, Australia
5
2
Princess Alexandra Hospital, Brisbane, Australia
6
3
Mater Research Institute, The University of Queensland at TRI, South Brisbane, Australia
7
4
The Translational Research Institute, Brisbane, Australia
8 9
Corresponding author :
10
Ken Ho MD, FRACP, FRCP (UK)
11
Translational Research Institute,
12
37 Kent Street
13
Woolloongabba, QLD, 4102
14
Phone: +61 7 3443 8066
15
Fax: +61 7 3443 7779
16
Email: [email protected]
17 18
Short title :
19
Glucocorticoids and human brown fat
20 21
Key words:
22
Brown fat, adipogenesis, glucocorticoids, thermogenesis
23 24
Word count abstract: 237
25 26 1 Copyright © 2014 by the Society for Endocrinology.
Page 2 of 26
JOE-14-0538.R1
27
Abstract
28
Clinical cases of glucocorticoid excess are characterised by increased fat mass and obesity through
29
the accumulation of white adipocytes. The effect of glucocorticoids on brown adipose growth and
30
function is unknown, and may contribute to the negative energy balance observed clinically. This
31
study aims to evaluate the effect of glucocorticoids on brown adipocyte proliferation, differentiation
32
and metabolic function. Human brown adipocytes sourced from supraclavicular fat biopsies were
33
grown in culture and differentiated to mature adipocytes. Human white adipocytes sourced from
34
subcutaneous abdominal fat biopsies were cultured as controls. Dexamethasone effects on brown
35
adipocyte growth, differentiation (Ucp1, Cidea, Pgc1α expression) and function (oxygen
36
consumption rate, OCR) were quantified. Dexamethasone (1 µM) significantly stimulated the
37
proliferation of brown and reduced that of white preadipocytes. During differentiation,
38
dexamethasone (at 0.1, 1 and 10 µM) stimulated the expression of Ucp1, Cidea and Pgc1α in a
39
concentration-dependent manner and enhanced by 4-6 fold the OCR of brown adipocytes.
40
Isoprenaline (100 nM) significantly enhanced (p
Accepted Preprint first posted on 10 November 2014 as Manuscript JOE-14-0538
JOE-14-0538.R1
The effects of glucocorticoids on human brown adipocytes
1 2
Johanna L Barclay1,4, Hadiya Agada1, Christina Jang1,2, Micheal Ward3, Neil Wetzig2, Ken KY Ho1,2,4
3 4
1
School of Medicine, University of Queensland, Herston, Australia
5
2
Princess Alexandra Hospital, Brisbane, Australia
6
3
Mater Research Institute, The University of Queensland at TRI, South Brisbane, Australia
7
4
The Translational Research Institute, Brisbane, Australia
8 9
Corresponding author :
10
Ken Ho MD, FRACP, FRCP (UK)
11
Translational Research Institute,
12
37 Kent Street
13
Woolloongabba, QLD, 4102
14
Phone: +61 7 3443 8066
15
Fax: +61 7 3443 7779
16
Email: [email protected]
17 18
Short title :
19
Glucocorticoids and human brown fat
20 21
Key words:
22
Brown fat, adipogenesis, glucocorticoids, thermogenesis
23 24
Word count abstract: 237
25 26 1 Copyright © 2014 by the Society for Endocrinology.
Page 2 of 26
JOE-14-0538.R1
27
Abstract
28
Clinical cases of glucocorticoid excess are characterised by increased fat mass and obesity through
29
the accumulation of white adipocytes. The effect of glucocorticoids on brown adipose growth and
30
function is unknown, and may contribute to the negative energy balance observed clinically. This
31
study aims to evaluate the effect of glucocorticoids on brown adipocyte proliferation, differentiation
32
and metabolic function. Human brown adipocytes sourced from supraclavicular fat biopsies were
33
grown in culture and differentiated to mature adipocytes. Human white adipocytes sourced from
34
subcutaneous abdominal fat biopsies were cultured as controls. Dexamethasone effects on brown
35
adipocyte growth, differentiation (Ucp1, Cidea, Pgc1α expression) and function (oxygen
36
consumption rate, OCR) were quantified. Dexamethasone (1 µM) significantly stimulated the
37
proliferation of brown and reduced that of white preadipocytes. During differentiation,
38
dexamethasone (at 0.1, 1 and 10 µM) stimulated the expression of Ucp1, Cidea and Pgc1α in a
39
concentration-dependent manner and enhanced by 4-6 fold the OCR of brown adipocytes.
40
Isoprenaline (100 nM) significantly enhanced (p
