Cold but not sympathomimetics activates human brown adipose tissue in vivo
Cold but not sympathomimetics activates human brown adipose tissue in vivo
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DOI：
10.1073/pnas.1207911109
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发表时间：
2012-06-19
影响因子：
11.1
通讯作者：
Kahn, C. Ronald
中科院分区：
文献类型：
--
作者：
Cypess, Aaron M.;Chen, Yih-Chieh;Kahn, C. Ronald
作为棕色脂肪组织（BAT）的潜在激活剂，轻度冷暴露和拟交感神经药物已被认为是肥胖和糖尿病的治疗方法，但它们是否激活相同的通路尚不清楚。在10名健康志愿者中，我们发现拟交感神经麻黄碱提高了血压，心率和能量消耗，并增加了多种循环代谢物，包括葡萄糖，胰岛素和甲状腺激素。冷暴露也会增加血压和能量消耗，但会降低心率，对代谢物的影响很小。重要的是，在每个志愿者中，通过F-18-氟脱氧葡萄糖PET-CT测量，寒冷增加了BAT的活性，而麻黄碱未能刺激BAT。因此，在导致交感神经系统广泛激活的剂量下，麻黄碱不会刺激人体的BAT。相比之下，轻度寒冷暴露会刺激BAT能量消耗，而其他全身效应较少，这表明寒冷会激活特定的交感神经通路。模拟BAT冷激活的药物可以提供一种有希望的治疗肥胖的方法，同时最大限度地减少全身效应。
As potential activators of brown adipose tissue (BAT), mild cold exposure and sympathomimetic drugs have been considered as treatments for obesity and diabetes, but whether they activate the same pathways is unknown. In 10 healthy human volunteers, we found that the sympathomimetic ephedrine raised blood pressure, heart rate, and energy expenditure, and increased multiple circulating metabolites, including glucose, insulin, and thyroid hormones. Cold exposure also increased blood pressure and energy expenditure, but decreased heart rate and had little effect on metabolites. Importantly, cold increased BAT activity as measured by F-18-fluorodeoxyglucose PET-CT in every volunteer, whereas ephedrine failed to stimulate BAT. Thus, at doses leading to broad activation of the sympathetic nervous system, ephedrine does not stimulate BAT in humans. In contrast, mild cold exposure stimulates BAT energy expenditure with fewer other systemic effects, suggesting that cold activates specific sympathetic pathways. Agents that mimic cold activation of BAT could provide a promising approach to treating obesity while minimizing systemic effects.