Glucocorticoids Acutely Increase Brown Adipose Tissue Activity in Humans, Revealing Species-Specific Differences in UCP-1 Regulation.
Glucocorticoids Acutely Increase Brown Adipose Tissue Activity in Humans, Revealing Species-Specific Differences in UCP-1 Regulation.
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DOI：
10.1016/j.cmet.2016.06.011
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发表时间：
2016-07-12
期刊：
影响因子：
29
通讯作者：
Stimson RH
中科院分区：
文献类型：
--
作者：
Ramage LE;Akyol M;Fletcher AM;Forsythe J;Nixon M;Carter RN;van Beek EJ;Morton NM;Walker BR;Stimson RH
棕色脂肪组织（BAT）在成年人中的发现为代谢疾病提供了一个新的治疗靶点;然而，对人类BAT的调控知之甚少。慢性糖皮质激素过量导致人类肥胖，而糖皮质激素抑制啮齿类动物的BAT激活。我们测试了糖皮质激素是否调节人类的BAT活性。在体内，糖皮质激素泼尼松龙在轻度寒冷暴露（16°C-17°C）期间急剧增加了瘦健康男性BAT对18氟脱氧葡萄糖的摄取（使用PET/CT测量）。此外，泼尼松龙增加锁骨上皮肤温度（使用红外热成像测量）和能量消耗在寒冷，但不温暖，暴露在瘦受试者。在体外，糖皮质激素增加异丙肾上腺素刺激的呼吸和UCP-1在人原代棕色脂肪细胞，但大大降低异丙肾上腺素刺激的呼吸和UCP-1在原代小鼠棕色和米色脂肪细胞。糖皮质激素对BAT功能的高度物种特异性调节可能对激活BAT以改善代谢健康的新型治疗方法的转化具有重要意义。糖皮质激素急性增加但慢性抑制人类BAT活性糖皮质激素增加人类棕色脂肪细胞中的UCP-1和呼吸糖皮质激素降低小鼠棕色和米色脂肪细胞中的UCP-1和呼吸BAT激活的调节存在物种特异性差异人类棕色脂肪组织（BAT）的调节尚不清楚。Ramage等人显示糖皮质激素通过增加UCP-1在人体内和体外急剧增加BAT。然而，糖皮质激素减少UCP-1在鼠米色/棕色脂肪细胞，确定物种特异性差异的BAT功能的调节。
The discovery of brown adipose tissue (BAT) in adult humans presents a new therapeutic target for metabolic disease; however, little is known about the regulation of human BAT. Chronic glucocorticoid excess causes obesity in humans, and glucocorticoids suppress BAT activation in rodents. We tested whether glucocorticoids regulate BAT activity in humans. In vivo, the glucocorticoid prednisolone acutely increased 18fluorodeoxyglucose uptake by BAT (measured using PET/CT) in lean healthy men during mild cold exposure (16°C–17°C). In addition, prednisolone increased supraclavicular skin temperature (measured using infrared thermography) and energy expenditure during cold, but not warm, exposure in lean subjects. In vitro, glucocorticoids increased isoprenaline-stimulated respiration and UCP-1 in human primary brown adipocytes, but substantially decreased isoprenaline-stimulated respiration and UCP-1 in primary murine brown and beige adipocytes. The highly species-specific regulation of BAT function by glucocorticoids may have important implications for the translation of novel treatments to activate BAT to improve metabolic health. Glucocorticoids acutely increase but chronically suppress BAT activity in humans Glucocorticoids increase UCP-1 and respiration in human brown adipocytes Glucocorticoids decrease UCP-1 and respiration in murine brown and beige adipocytes Species-specific differences exist in the regulation of BAT activation The regulation of brown adipose tissue (BAT) in humans is not well understood. Ramage et al. show that glucocorticoids acutely increase BAT in vivo and in vitro in humans through increasing UCP-1. However, glucocorticoids decrease UCP-1 in murine beige/ brown adipocytes, identifying species-specific differences in the regulation of BAT function.