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

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. Randomized crossover trial

糖皮质激素（Glucocorticoids, GCs）是一类应用广泛的抗炎药物，其伴随的不良代谢效应包括胰岛素抵抗与体重增加。既往研究提示，糖皮质激素可能对啮齿类动物及人类的棕色脂肪组织（brown adipose tissue, BAT）产生负面影响。本研究证实，对人类志愿者给予大剂量糖皮质激素治疗后，受试者的静息能量消耗（resting energy expenditure, REE）升高，但棕色脂肪组织活性并未降低。与上述生理学结果一致，体内实验中糖皮质激素并未显著改变人类棕色脂肪组织的基因表达水平。然而，对骨骼肌（skeletal muscle）进行RNA测序（RNA-sequencing）后发现，糖皮质激素可上调参与钙循环（calcium cycling）及呼吸链（respiratory chain）过程的酶类表达。综合以上数据，本研究提示，糖皮质激素暴露后能量消耗（energy expenditure, EE）的升高是由骨骼肌介导的，而非棕色脂肪组织活性改变所致。本研究为随机交叉试验