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Effect of high-dose glucocorticoid treatment on human brown adipose tissue activity: a randomised, double-blinded, placebo-controlled cross-over trial in healthy men

ABSTRACT: Glucocorticoids (GCs) are widely applied anti-inflammatory drugs that are associated with adverse metabolic effects including insulin resistance and weight gain. Previous research indicated that GCs may negatively impact brown adipose tissue (BAT) in rodents and humans. Here, we demonstrate that treatment of human volunteers with high doses of GCs increases resting energy expenditure (REE) but does not reduce BAT activity. In line with the physiological results, gene expression in human BAT was not significantly altered by GCs in vivo. However, the RNA-sequencing of skeletal muscle revealed that GCs increase the expression of enzymes involved in calcium cycling as well as the respiratory chain. Collectively, these data suggest that the raise of EE after GCs exposure is mediated by skeletal muscle rather than a change in BAT activity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE220158 | GEO | 2023/09/04

REPOSITORIES: GEO

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Project description:Background: The prevalence of type 2 diabetes has increased dramatically in recent decades. Increasing brown adipose tissue (BAT) mass and activity has recently emerged as an interesting approach to not only increase energy expenditure, but also improve glucose homeostasis. BAT can be recruited by prolonged cold exposure in lean, healthy humans. Here, we tested whether cold acclimation could have therapeutic value for patients with type 2 diabetes by improving insulin sensitivity. Methods: Eight type 2 diabetic patients (age 59.3±5.8 years, BMI 29.8±3.2 kg/m2) followed a cold acclimation protocol, consisting of intermittent cold exposure (6 hours/day, 14-14.5 °C) for 12 consecutive days. Before and after cold acclimation, cold-induced BAT activity was assessed by [18F]FDG-PET/CT scanning, insulin sensitivity at thermoneutrality by a hyperinsulinemic-euglycemic clamp, and muscle and WAT biopsies were taken. Results: Cold-induced BAT activity was low, but increased in all patients upon cold acclimation (SUV from 0.40±0.29 to 0.63±0.78, p<0.05). Interestingly, insulin sensitivity showed a very pronounced 40% increase upon cold acclimation (glucose rate of disappearance from 14.9±4.1 to 20.5±6.9 μmol kg-1 min-1, p<0.05). A 40% increase in insulin sensitivity cannot be explained by BAT glucose uptake, in fact basal skeletal muscle GLUT4 content and translocation was markedly increased after cold acclimation, without effects on insulin signaling or AMPk activation. Conclusions: Regular mild cold exposure has marked effects on insulin sensitivity, which are accompanied by small increases in BAT activity and more pronounced effects on skeletal muscle. These data suggest a novel therapeutic option for the treatment of type 2 diabetes. Microarray analysis was performed on abdominal subcutaneous white adipose tissue samples from human type 2 diabetic patients before, and after 10 days of cold acclimation. A total of 14 samples, from 7 subjects, were used for the microarray analysis.

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Effect of high-dose glucocorticoid treatment on human brown adipose tissue activity: a randomised, double-blinded, placebo-controlled cross-over trial in healthy men

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