Molecular and cellular characteristics of brown

棕色的分子和细胞特征

• 批准号: 15081201
• 负责人: SAITO Masayuki
• 金额: $ 49.15万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15081201/
• 关键词: brown adipose tissue; β-adrenoceptor; leptin; UCP1; white fat; thermogenesis; obesity; sympathetic nerve; 体脂肪; FDG-PET; 寒冷刺激; 脱共役蛋白質; 褐色脂肪細胞; 白色脂肪細胞; UCP; エネルギー消費; 遺伝子

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

我们研究了棕色脂肪组织（BAT）产热在调节小鼠和狗的能量底物代谢和肥胖中的作用，特别关注BAT产热的关键分子UCP 1的交感神经调节.用存在于脂肪细胞中的β3-肾上腺素受体激动剂处理，增加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，但在UCP 1敲除小鼠中没有。当小鼠用瘦素（一种主要的内源性厌食信号分子）处理时，也发现了类似的产热和抗肥胖作用.还在犬中检查了β3-肾上腺素能刺激的作用。每天用β3-肾上腺素受体激动剂治疗肥胖比格犬，通过CT估计，体脂含量显著降低，皮下脂肪组织中UCP 1表达明显增加。 ...更多信息 以上结果表明UCP 1依赖的BAT产热在β3-肾上腺素受体激动剂和瘦素的减肥作用中以及在能量平衡的调节中起重要作用.研究了BAT中与产热相关的葡萄糖利用，特别关注UCP 1的作用。去甲肾上腺素（NA）增加WT小鼠组织AMP水平、5 '-AMP活化蛋白激酶活性和BAT对2-脱氧葡萄糖（2-DG）的摄取，而NA的这些刺激作用在UCP 1-KO小鼠中明显减弱。因此，交感神经刺激下BAT对葡萄糖的利用是由于UCP 1和AMP-激酶的串联激活，从而反映了体内BAT的活性.通过正电子发射断层扫描监测健康成年志愿者的组织氟脱氧葡萄糖摄取，还检查了脂肪组织中的葡萄糖利用，发现冷暴露后葡萄糖利用增强，肥胖者的葡萄糖利用低于瘦受试者。这些发现与成年人中不存在BAT的公认观点相反，表明BAT在人类的能量代谢中发挥着重要作用，就像在小鼠和狗中一样。少

项目成果

Human brown adipose tissue evaluated by FDG-PET : activation by cold exposure

通过 FDG-PET 评估人棕色脂肪组织：冷暴露激活

• 发表时间: 2007
• 作者: Saito M;Okamatsu-Ogura Y;Tsujisaki M;Kaji T;Nakada K.
• 通讯作者: Nakada K.

Noradrenaline stimulates glucose uptake in brown adipose tisue through the activation of UCP1 and AMP kinase.

去甲肾上腺素通过激活 UCP1 和 AMP 激酶来刺激棕色脂肪组织中的葡萄糖摄取。

• 发表时间: 2005
• 作者: M. Saito;K. Inokuma;C. Toda;Y. Okamatsu;K. Kimura
• 通讯作者: K. Kimura

Indispensable role of UCP1 for aniti-obesity effect of BETA-3-adrenergic agonists.

UCP1 对于 BETA-3-肾上腺素能激动剂的抗肥胖作用起着不可或缺的作用。

• 发表时间: 2004
• 作者: M. Saito;K. Inokuma. A. Omachi;Y. Matsushita;K. Kimura;H. Yamashita
• 通讯作者: H. Yamashita

Postprandial changes in leptin concentrations of cerebrospinal fluid in dogs during development of obesity

肥胖发展过程中犬脑脊液瘦素浓度的餐后变化

• 发表时间: 2006
• 期刊: Am. J. Vet. Res. 67
• 作者: Nishii N;Nodake H;Takasu M;Soe O;Ohba Y;Maeda S;Ohtsuka Y;Honjo T;Saito M;Kitagawa H.
• 通讯作者: Kitagawa H.

Minor role of brown fatthermogenesis in IL-1 beta-inducedfever

棕色脂肪产热在 IL-1 β 诱导的发热中的次要作用

• 发表时间: 2007
• 作者: Okamatsu-Ogura;Y.;Kitao;N.;Kimura,K.;Saito;M.
• 通讯作者: M.