Effects of glucocorticoids on human brown adipocytes.
Clinical cases of glucocorticoid (GC) excess are characterized by increased fat mass and obesity through the accumulation of white adipocytes. The effects of GCs on growth and function of brown adipose tissue are unknown and may contribute to the negative energy balance observed clinically. This study aims to evaluate the effect of GCs on proliferation, differentiation, and metabolic function of brown adipocytes. Human brown adipocytes sourced from supraclavicular fat biopsies were grown in culture and differentiated to mature adipocytes. Human white adipocytes sourced from subcutaneous abdominal fat biopsies were cultured as controls. Effects of dexamethasone on growth, differentiation (UCP1, CIDEA, and PPARGC1A expression), and function (oxygen consumption rate (OCR)) of brown adipocytes were quantified. Dexamethasone (1 μM) significantly stimulated the proliferation of brown preadipocytes and reduced that of white preadipocytes. During differentiation, dexamethasone (at 0.1, 1, and 10 μM) stimulated the expression of UCP1, CIDEA, and PPARGC1A in a concentration-dependent manner and enhanced by fourfold to sixfold the OCR of brown adipocytes. Isoprenaline (100 nM) significantly increased (P<0.05) expression of UCP1 and OCR of brown adipocytes. These effects were significantly reduced (P<0.05) by dexamethasone. Thus, we show that dexamethasone stimulates the proliferation, differentiation, and function of human brown adipocytes but inhibits adrenergic stimulation of the functioning of brown adipocytes. We conclude that GCs exert complex effects on development and function of brown adipocytes. These findings provide strong evidence for an effect of GCs on the biology of human brown adipose tissue (BAT) and for the involvement of the BAT system in the metabolic manifestation of Cushing's syndrome.
School of MedicineUniversity of Queensland, Herston, Queensland, AustraliaMater Research InstituteThe University of Queensland at TRI, South Brisbane, Queensland, AustraliaThe Translational Research Institute37 Kent Street, Woolloongabba, Brisbane, Queensland, AustraliaPrincess Alexandra HospitalBrisbane, Queensland, Australia School of MedicineUniversity of Queensland, Herston, Queensland, AustraliaMater Research InstituteThe University of Queensland at TRI, South Brisbane, Queensland, AustraliaThe Translational Research Institute37 Kent Street, Woolloongabba, Brisbane, Queensland, AustraliaPrincess Alexandra HospitalBrisbane, Queensland, Australia School of MedicineUniversity of Queensland, Herston, Queensland, AustraliaMater Research InstituteThe University of Queensland at TRI, South Brisbane, Queensland, AustraliaThe Translational Research Institute37 Kent Street, Woolloongabba, Brisbane, Queensland, AustraliaPrincess Alexandra HospitalBrisbane, Queensland, Australia.
Johanna L
JL
Barclay
School of MedicineUniversity of Queensland, Herston, Queensland, AustraliaMater Research InstituteThe University of Queensland at TRI, South Brisbane, Queensland, AustraliaThe Translational Research Institute37 Kent Street, Woolloongabba, Brisbane, Queensland, AustraliaPrincess Alexandra HospitalBrisbane, Queensland, Australia School of MedicineUniversity of Queensland, Herston, Queensland, AustraliaMater Research InstituteThe University of Queensland at TRI, South Brisbane, Queensland, AustraliaThe Translational Research Institute37 Kent Street, Woolloongabba, Brisbane, Queensland, AustraliaPrincess Alexandra HospitalBrisbane, Queensland, Australia.
Hadiya
H
Agada
School of MedicineUniversity of Queensland, Herston, Queensland, AustraliaMater Research InstituteThe University of Queensland at TRI, South Brisbane, Queensland, AustraliaThe Translational Research Institute37 Kent Street, Woolloongabba, Brisbane, Queensland, AustraliaPrincess Alexandra HospitalBrisbane, Queensland, Australia School of MedicineUniversity of Queensland, Herston, Queensland, AustraliaMater Research InstituteThe University of Queensland at TRI, South Brisbane, Queensland, AustraliaThe Translational Research Institute37 Kent Street, Woolloongabba, Brisbane, Queensland, AustraliaPrincess Alexandra HospitalBrisbane, Queensland, Australia.
Christina
C
Jang
School of MedicineUniversity of Queensland, Herston, Queensland, AustraliaMater Research InstituteThe University of Queensland at TRI, South Brisbane, Queensland, AustraliaThe Translational Research Institute37 Kent Street, Woolloongabba, Brisbane, Queensland, AustraliaPrincess Alexandra HospitalBrisbane, Queensland, Australia School of MedicineUniversity of Queensland, Herston, Queensland, AustraliaMater Research InstituteThe University of Queensland at TRI, South Brisbane, Queensland, AustraliaThe Translational Research Institute37 Kent Street, Woolloongabba, Brisbane, Queensland, AustraliaPrincess Alexandra HospitalBrisbane, Queensland, Australia.
Micheal
M
Ward
School of MedicineUniversity of Queensland, Herston, Queensland, AustraliaMater Research InstituteThe University of Queensland at TRI, South Brisbane, Queensland, AustraliaThe Translational Research Institute37 Kent Street, Woolloongabba, Brisbane, Queensland, AustraliaPrincess Alexandra HospitalBrisbane, Queensland, Australia.
Neil
N
Wetzig
School of MedicineUniversity of Queensland, Herston, Queensland, AustraliaMater Research InstituteThe University of Queensland at TRI, South Brisbane, Queensland, AustraliaThe Translational Research Institute37 Kent Street, Woolloongabba, Brisbane, Queensland, AustraliaPrincess Alexandra HospitalBrisbane, Queensland, Australia School of MedicineUniversity of Queensland, Herston, Queensland, AustraliaMater Research InstituteThe University of Queensland at TRI, South Brisbane, Queensland, AustraliaThe Translational Research Institute37 Kent Street, Woolloongabba, Brisbane, Queensland, AustraliaPrincess Alexandra HospitalBrisbane, Queensland, Australia School of MedicineUniversity of Queensland, Herston, Queensland, AustraliaMater Research InstituteThe University of Queensland at TRI, South Brisbane, Queensland, AustraliaThe Translational Research Institute37 Kent Street, Woolloongabba, Brisbane, Queensland, AustraliaPrincess Alexandra HospitalBrisbane, Queensland, Australia k.ho@uq.edu.au.
Ken K Y
KK
Ho
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism; D052437:Adipocytes, Brown / Q000187:drug effects* / Q000502:physiology; D059331:Adrenergic Neurons / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects / Q000235:genetics; D000071256:Uncoupling Protein 1
D005938:Glucocorticoids; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1; D003907:Dexamethasone; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C468386:HSD11B1 protein, human
adipogenesis; brown fat; glucocorticoids; thermogenesis