Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91, Stockholm, Sweden.
Karolinska Experimental Research and Imaging Center, Karolinska University Hospital, Solna, SE-171 76, Stockholm, Sweden.
Mol Metab. 2017 Mar 30;6(6):611-619. doi: 10.1016/j.molmet.2017.02.006. eCollection 2017 Jun.
Today, the presence and activity of brown adipose tissue (BAT) in adult humans is generally equated with the induced accumulation of [2-F]2-fluoro-2-deoxy-d-glucose ([F]FDG) in adipose tissues, as investigated by positron emission tomography (PET) scanning. In reality, PET-FDG is currently the only method available for 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 [F]FDG uptake by PET and by tissue [H]-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 β-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 β-adrenergic treatment was UCP1 dependent. Thus, therapeutically, UCP1 activity is required for any anti-diabetic effect of BAT activation.
如今，通过正电子发射断层扫描（PET）扫描发现，成年人体内棕色脂肪组织（BAT）的存在和活性通常与脂肪组织中[2-F]2-氟-2-脱氧-d-葡萄糖（[F]FDG）的诱导积累有关。实际上，目前 PET-FDG 是唯一可用于定量测量成年人体内 BAT 活性的方法。其基本假设是葡萄糖摄取反映了组织的产热活性。
为了检验这一基本假设，我们通过 PET 扫描和组织[H]-2-脱氧-d-葡萄糖摄取，在野生型和 UCP1（-/-）小鼠中（即具有或不具有 BAT 独特的产热和耗卡路里能力的小鼠中）研究了[F]FDG 的摄取。
出乎意料的是，我们发现β-肾上腺素能诱导（由 CL-316,243 诱导）的葡萄糖摄取与 UCP1 无关。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不是继发于产热，而是由独立的细胞信号传导控制，这里证明是通过先前描述的 KU-0063794 敏感的 mTOR 途径介导的。
因此，PET-FDG 扫描不仅揭示了活跃的 BAT 沉积物，而且还揭示了任何具有肾上腺素能介导的葡萄糖摄取途径的组织。相比之下，我们发现，长期β-肾上腺素能治疗的葡萄糖摄取改善效果是 UCP1 依赖性的。因此，在治疗上，UCP1 活性是 BAT 激活产生任何抗糖尿病作用所必需的。
