Section of Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
Proc Natl Acad Sci U S A. 2012 Jun 19;109(25):10001-5. doi: 10.1073/pnas.1207911109. Epub 2012 Jun 4.
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 (18)F-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.
作为棕色脂肪组织 (BAT) 的潜在激活剂，轻度寒冷暴露和拟交感神经药物已被认为可用于治疗肥胖症和糖尿病，但它们是否激活相同的途径尚不清楚。在 10 名健康的人类志愿者中，我们发现拟交感神经麻黄碱会升高血压、心率和能量消耗，并增加多种循环代谢物，包括葡萄糖、胰岛素和甲状腺激素。寒冷暴露也会升高血压和能量消耗，但会降低心率，对代谢物几乎没有影响。重要的是，寒冷会增加每个志愿者的（18）F-氟脱氧葡萄糖正电子发射断层扫描（PET-CT）测量的 BAT 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，麻黄碱不会刺激人类的 BAT。相比之下，轻度寒冷暴露会刺激 BAT 的能量消耗，而其他全身影响较小，这表明寒冷会激活特定的交感神经通路。模仿 BAT 冷激活的药物可能为治疗肥胖症提供一种有前途的方法，同时最大限度地减少全身影响。
