β(3)-Adrenergically induced glucose uptake in brown adipose tissue is independent of UCP1 presence or activity: Mediation through the mTOR pathway.
β(3)-Adrenergically induced glucose uptake in brown adipose tissue is independent of UCP1 presence or activity: Mediation through the mTOR pathway.
复制标题
DOI：
10.1016/j.molmet.2017.02.006
复制
发表时间：
2017-06
影响因子：
8.1
通讯作者：
Bengtsson T
中科院分区：
文献类型：
--
作者：
Olsen JM;Csikasz RI;Dehvari N;Lu L;Sandström A;Öberg AI;Nedergaard J;Stone-Elander S;Bengtsson T
如今，成人中棕色脂肪组织（BAT）的存在和活性通常等同于脂肪组织中[2- 18 F]2-氟-2-脱氧-d-葡萄糖（[18 F]FDG）的诱导积累，如正电子发射断层扫描（PET）所研究的。实际上，PET-FDG是目前唯一可用于成年人体内BAT活性定量的方法。基本假设是葡萄糖摄取反映了组织的产热活动。为了检验这一基本假设，我们在此跟踪了野生型和UCP 1（-/-）小鼠（即具有或不具有BAT独特产热和卡路里消耗能力的小鼠）中PET和组织[3 H]-2-脱氧-d-葡萄糖摄取的[18 F]FDG摄取。出乎意料的是，我们发现β3-肾上腺素能诱导（CL-316，243）的葡萄糖摄取不依赖于UCP 1。因此，尽管PET-FDG扫描充分反映了葡萄糖摄取，但这种急性葡萄糖摄取并非继发于产热，而是由独立的细胞信号传导控制，在此证明通过先前描述的KU-0063794敏感性mTOR途径介导。因此，PET-FDG扫描并不完全显示活性BAT沉积物，而是显示具有肾上腺素能介导的葡萄糖摄取途径的任何组织。相反，我们发现延长β3-肾上腺素能治疗的显著葡萄糖摄取改善作用是UCP 1依赖性的。因此，在治疗上，UCP 1活性是BAT激活的任何抗糖尿病作用所必需的。BAT中的β3肾上腺素能葡萄糖摄取不依赖于UCP 1。葡萄糖摄取不是继发于产热，而是通过mTOR途径。葡萄糖摄取和产热都需要充分影响葡萄糖稳态。
Today, the presence and activity of brown adipose tissue (BAT) in adult humans is generally equated with the induced accumulation of [2-18F]2-fluoro-2-deoxy-d-glucose ([18F]FDG) in adipose tissues, as investigated by positron emission tomography (PET) scanning. In reality, PET-FDG is currently the only method available for in vivo quantification of BAT activity in adult humans. The underlying assumption is that the glucose uptake reflects the thermogenic activity of the tissue. To examine this basic assumption, we here followed [18F]FDG uptake by PET and by tissue [3H]-2-deoxy-d-glucose uptake in wildtype and UCP1(−/−) mice, i.e. in mice that do or do not possess the unique thermogenic and calorie-consuming ability of BAT. Unexpectedly, we found that β3-adrenergically induced (by CL-316,243) glucose uptake was UCP1-independent. Thus, whereas PET-FDG scans adequately reflect glucose uptake, this acute glucose uptake is not secondary to thermogenesis but is governed by an independent cellular signalling, here demonstrated to be mediated via the previously described KU-0063794-sensitive mTOR pathway. Thus, PET-FDG scans do not exclusively reveal active BAT deposits but rather any tissue possessing an adrenergically-mediated glucose uptake pathway. In contrast, we found that the marked glucose uptake-ameliorating effect of prolonged β3-adrenergic treatment was UCP1 dependent. Thus, therapeutically, UCP1 activity is required for any anti-diabetic effect of BAT activation. β3-adrenergically glucose uptake in BAT is UCP1-independent. Glucose uptake is not secondary to thermogenesis but is through the mTOR pathway. Both glucose uptake and thermogenesis are needed to fully effect glucose homeostasis.