Brown adipose tissue lipoprotein and glucose disposal is not determined by thermogenesis in uncoupling protein 1-deficient mice
Brown adipose tissue lipoprotein and glucose disposal is not determined by thermogenesis in uncoupling protein 1-deficient mice
复制标题
DOI：
10.1194/jlr.ra119000455
复制
发表时间：
2020-11-01
影响因子：
6.5
通讯作者：
Heeren, Joerg
中科院分区：
文献类型：
--
作者：
Fischer, Alexander W.;Behrens, Janina;Heeren, Joerg
适应性产热高度依赖解偶联蛋白1(UCP1)，这是一种存在于棕色脂肪组织(BAT)和白色脂肪组织(WAT)中的生热脂肪细胞表达的蛋白质。人和小鼠蝙蝠的产热能力可以通过正电子发射断层扫描-计算机断层扫描定量摄取F-18-脱氧葡萄糖或脂质示踪剂来测量。BAT的激活通常是在冷暴露或用β-3肾上腺素能受体激动剂如CL316,243(CL)治疗的情况下进行的研究。目前，尚不清楚冷刺激摄取葡萄糖或脂质示踪剂是否是UCP1介导的产热的良好替代标记物。在使用放射性标记示踪剂的代谢研究中，我们发现，与保持在低温下的WT小鼠相比，Ucp1(-/-)轻度冷激活BAT的葡萄糖摄取量增加。相反，在持续冷暴露或CL处理实现完全生热激活后，检测到较低的葡萄糖处置。相反，在UCP1缺陷的小鼠中，长期激活的生热脂肪组织对脂蛋白衍生脂肪酸的摄取显著增加。这种效应与Ucp1(-/-)小鼠脂肪组织中更高的交感神经张力有关，BAT和WAT中产热基因水平的提高表明了这一点。因此，葡萄糖和脂蛋白的处理并不一定反映UCP1依赖的生热活性，但尤其是脂质摄取反映了脂肪组织的交感激活。
Adaptive thermogenesis is highly dependent on uncoupling protein 1 (UCP1), a protein expressed by thermogenic adipocytes present in brown adipose tissue (BAT) and white adipose tissue (WAT). Thermogenic capacity of human and mouse BAT can be measured by positron emission tomography-computed tomography quantifying the uptake of F-18-fluodeoxyglucose or lipid tracers. BAT activation is typically studied in response to cold exposure or treatment with beta-3-adrenergic receptor agonists such as CL316,243 (CL). Currently, it is unknown whether cold-stimulated uptake of glucose or lipid tracers is a good surrogate marker of UCP1-mediated thermogenesis. In metabolic studies using radiolabeled tracers, we found that glucose uptake is increased in mildly cold-activated BAT of Ucp1(-/-) versus WT mice kept at subthermoneutral temperature. Conversely, lower glucose disposal was detected after full thermogenic activation achieved by sustained cold exposure or CL treatment. In contrast, uptake of lipoprotein-derived fatty acids into chronically activated thermogenic adipose tissues was substantially increased in UCP1-deficient mice. This effect is linked to higher sympathetic tone in adipose tissues of Ucp1(-/-) mice, as indicated by elevated levels of thermogenic genes in BAT and WAT. Thus, glucose and lipoprotein handling does not necessarily reflect UCP1-dependent thermogenic activity, but especially lipid uptake rather mirrors sympathetic activation of adipose tissues.