Effects of glucocorticoids on human brown adipocytes

Barclay, Johanna L.; Agada, Hadiya; Jang, Choon‐Gon; Ward, Micheal; Wetzig, Neil; Ho, Ken K. Y.

doi:10.1530/joe-14-0538

Cited by 47 publications

(41 citation statements)

References 17 publications

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“…However, in adult rodents, glucocorticoids inhibit BAT [23] by interfering with adrenergic signaling [24], [25]. Human data are scarce with one study reporting dexamethasone-induced inhibition of UCP1 expression and metabolic rate in human brown adipocytes in vitro [26], and another reporting BAT activation following administration of the synthetic glucocorticoid prednisolone in vivo [9]. In our study, we chose hydrocortisone to model a physiological acute surge of cortisol, as seen during the perinatal period and at times of acute stress.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoids modulate human brown adipose tissue thermogenesis in vivo

et al. 2017

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IntroductionBrown adipose tissue (BAT) is a thermogenic organ with substantial metabolic capacity and has important roles in the maintenance of body weight and metabolism. Regulation of BAT is primarily mediated through the β-adrenoceptor (β-AR) pathway. The in vivo endocrine regulation of this pathway in humans is unknown. The objective of our study was to assess the in vivo BAT temperature responses to acute glucocorticoid administration.MethodsWe studied 8 healthy male volunteers, not pre-selected for BAT presence or activity and without prior BAT cold-activation, on two occasions, following an infusion with hydrocortisone (0.2 mg.kg− 1.min− 1 for 14 h) and saline, respectively. Infusions were given in a randomized double-blind order. They underwent assessment of supraclavicular BAT temperature using infrared thermography following a mixed meal, and during β-AR stimulation with isoprenaline (25 ng.kg fat-free mass− 1.min− 1 for 60 min) in the fasting state.ResultsDuring hydrocortisone infusion, BAT temperature increased both under fasting basal conditions and during β-AR stimulation. We observed a BAT temperature threshold, which was not exceeded despite maximal β-AR activation. We conclude that BAT thermogenesis is present in humans under near-normal conditions. Glucocorticoids modulate BAT function, representing important physiological endocrine regulation of body temperature at times of acute stress.

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Section: Discussionmentioning

confidence: 99%

Glucocorticoids modulate human brown adipose tissue thermogenesis in vivo

et al. 2017

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“…There is some evidence that both adiponectin and GR are expressed in BAT, and therefore it is reasonable to hypothesize that the levels of GR within this tissue would be reduced in the present adipocyte GR knockdown mice (Iacobellis et al, 2013; Viengchareun et al, 2001; Zhang et al, 2002). While dexamethasone reduces the proliferation of human white adipocytes, it stimulates proliferation of human brown adipocytes (Barclay et al, 2015). Furthermore, in BAT, 11β-HSD1, which amplifies local glucocorticoid activity within the tissue, has profound effects on BAT function (Liu et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Adipocyte glucocorticoid receptors mediate fat-to-brain signaling

Kloet

Krause

Solomon

et al. 2015

Psychoneuroendocrinology

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Stress-related (e.g., depression) and metabolic pathologies (e.g., obesity) are important and often co-morbid public health concerns. Here we identify a connection between peripheral glucocorticoid receptor (GR) signaling originating in fat with the brain control of both stress and metabolism. Mice with reduced adipocyte GR hypersecrete glucocorticoids following acute psychogenic stress and are resistant to diet-induced obesity. This hypersecretion gives rise to deficits in responsiveness to exogenous glucocorticoids, consistent with reduced negative feedback via adipocytes. Increased stress reactivity occurs in the context of elevated hypothalamic expression of hypothalamic-pituitary-adrenal (HPA) axis-excitatory neuropeptides and in the absence of altered adrenal sensitivity, consistent with a central cite of action. Our results identify a novel mechanism whereby activation of the adipocyte GR promotes peripheral energy storage while inhibiting the HPA axis, and provide functional evidence for a fat-to-brain regulatory feedback network that serves to regulate not just homeostatic energy balance but also responses to psychogenic stimuli.

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“…In mice, an impairment of mitochondrial function has been related to increased epididymal adiposity after GC treatment (94). Recent in vitro data showed that dexamethasone induces proliferation, differentiation and basal metabolic activity of human brown adipocytes but inhibits their function under adrenergic stimulation (95).…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

Metabolic comorbidities in Cushing's syndrome

Ferraú

Korbonits

2015

European Journal of Endocrinology

149

121

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Cushing's syndrome (CS) patients have increased mortality primarily due to cardiovascular events induced by glucocorticoid (GC) excess-related severe metabolic changes. Glucose metabolism abnormalities are common in CS due to increased gluconeogenesis, disruption of insulin signalling with reduced glucose uptake and disposal of glucose and altered insulin secretion, consequent to the combination of GCs effects on liver, muscle, adipose tissue and pancreas. Dyslipidaemia is a frequent feature in CS as a result of GC-induced increased lipolysis, lipid mobilisation, liponeogenesis and adipogenesis. Protein metabolism is severely affected by GC excess via complex direct and indirect stimulation of protein breakdown and inhibition of protein synthesis, which can lead to muscle loss. CS patients show changes in body composition, with fat redistribution resulting in accumulation of central adipose tissue. Metabolic changes, altered adipokine release, GC-induced heart and vasculature abnormalities, hypertension and atherosclerosis contribute to the increased cardiovascular morbidity and mortality. In paediatric CS patients, the interplay between GC and the GH/IGF1 axis affects growth and body composition, while in adults it further contributes to the metabolic derangement. GC excess has a myriad of deleterious effects and here we attempt to summarise the metabolic comorbidities related to CS and their management in the perspective of reducing the cardiovascular risk and mortality overall.

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Effects of glucocorticoids on human brown adipocytes

Cited by 47 publications

References 17 publications

Glucocorticoids modulate human brown adipose tissue thermogenesis in vivo

Glucocorticoids modulate human brown adipose tissue thermogenesis in vivo

Adipocyte glucocorticoid receptors mediate fat-to-brain signaling

Metabolic comorbidities in Cushing's syndrome

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