Molecular and cellular characteristics of brown

我们研究了棕色脂肪组织（brown adipose tissue， BAT）生热在小鼠和狗的能量底物代谢和肥胖调节中的作用，特别关注了交感神经对BAT生热的关键分子UCP1的调节。用脂肪细胞中存在的β3-肾上腺素能受体激动剂治疗，增加了BAT产热、脂质动员和全身能量消耗，而对食物摄入没有显著影响，最终导致野生型（WT）小鼠的白色脂肪重量和脂肪细胞大小显著减少，而在ucp1敲除小鼠中则没有。用瘦素（一种主要的内源性厌食信号分子）治疗小鼠时，也发现了类似的产热和抗肥胖作用。β3-肾上腺素能刺激对狗的影响也进行了研究。每天用β3-肾上腺素能受体激动剂治疗肥胖的比格犬，通过CT估计其体脂含量显著降低，皮下脂肪组织中UCP1表达明显。这些结果表明，ucp1依赖性BAT产热作用在β3-肾上腺素受体激动剂和瘦素的抗肥胖作用和能量平衡调节中具有重要作用。研究了BAT中产热相关的葡萄糖利用，特别关注UCP1的作用。在WT小鼠中，去甲肾上腺素（NA）增加了组织AMP水平、5′-AMP激活的蛋白激酶活性和2-脱氧葡萄糖（2-DG）对BAT的摄取，而在UCP1-KO小鼠中，NA的这些刺激作用大大减弱。因此，BAT中交感刺激的葡萄糖利用是由于UCP1和amp激酶的连续激活，从而反映了BAT在体内的活性。葡萄糖进入脂肪组织的利用也通过正电子发射断层扫描监测健康成人志愿者的组织氟脱氧葡萄糖摄取，发现在寒冷暴露后，肥胖的人比瘦的人更低。这些发现与人们普遍认为的BAT在成年人中不存在的观点相反，表明BAT在人类的能量代谢中发挥着重要作用，就像在老鼠和狗身上一样。少

We have studied the role of brown adipose tissue (BAT) thermogenesis in the regulation of energy substrate metabolism and adiposity in mice and dogs, particularly focusing on the sympathetic nerve regulation of UCP1, a key molecule of BAT thermogenesis.1. Treatment with an agonist for β3-adrenoceptor, which is present in adipocytes, increased BAT thermogenesis, lipid mobilization and whole body energy expenditure without notable effects on food intake, finally resulting in a marked reduction of white fat weight and the size of adipocytes in wild-type (WT), but not in UCP1-knockout, mice. Similar thermogenic and anti-obesity effects were also found when mice were treated with leptin, a major endogenous anorectic signal molecule.2. The effects of β3-adrenergic stimulation were also examined in dogs. Daily treatment of obese beagle dogs with a β3-adrenoceptor agonist resulted in a marked reduction of body fat content estimated by CT, and apparent UCP1 expression in subcutaneous adipose ti … More ssue.All these results indicate a significant role of UCP1-dependent BAT thermogenesis in the anti-obesity effect of β3-adrenoceptor agonists and leptin, and in the regulation of energy balance.3. The thermogenesis-linked glucose utilization in BAT was studied particularly focusing on the role of UCP1. Noradrenaline (NA) increased tissue AMP levels, 5'-AMP-activated protein kinase activity, and 2-deoxyglucose (2-DG) uptake into BAT in WT mice, while these stimulatory effects of NA were much attenuated in UCP1-KO mice. Thus, the sympathetically stimulated glucose utilization in BAT is due to the serial activation of UCP1 and AMP-kinase, and thereby reflects the BAT activity in vivo.4. Glucose utilization into adipose tissue was also examined monitoring tissue fluoro-deoxyglucose uptake by positron emission tomography in healthy adult volunteers, and found to be enhanced after cold exposure and lower in obese than lean subjects. These findings, being against a well-accepted idea that BAT is absent in adult humans, suggest a significant role of BAT in energy metabolism in man, as in the mouse and dog. Less