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在非寒战性产热的肾上腺素能刺激过程中,UCP1基因敲除小鼠和UCP1基因野生型小鼠棕色脂肪组织中[F]FDG摄取的差异。

Differences in [F]FDG uptake in BAT of UCP1 -/- and UCP1 +/+ during adrenergic stimulation of non-shivering thermogenesis.

作者信息

McHugh Christian T, Garside John, Barkes Jared, Frank Jonathan, Dragicevich Constance, Yuan Hong, Branca Rosa T

机构信息

Department of Physics and Astronomy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Biomedical Research Imaging Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

出版信息

EJNMMI Res. 2020 Nov 7;10(1):136. doi: 10.1186/s13550-020-00726-x.

Abstract

BACKGROUND

Brown adipose tissue (BAT) is a fat tissue found in most mammals that helps regulate energy balance and core body temperature through a sympathetic process known as non-shivering thermogenesis. BAT activity is commonly detected and quantified in [F]FDG positron emission tomography/computed tomography (PET/CT) scans, and radiotracer uptake in BAT during adrenergic stimulation is often used as a surrogate measure for identifying thermogenic activity in the tissue. BAT thermogenesis is believed to be contingent upon the expression of the protein UCP1, but conflicting results have been reported in the literature concerning [F]FDG uptake within BAT of mice with and without UCP1. Differences in animal handling techniques such as feeding status, type of anesthetic, type of BAT stimulation, and estrogen levels were identified as possible confounding variables for [F]FDG uptake. In this study, we aimed to assess differences in BAT [F]FDG uptake between wild-type and UCP1-knockout mice using a protocol that minimizes possible variations in BAT stimulation caused by different stress responses to mouse handling.

RESULTS

[F]FDG PET/CT scans were run on mice that were anesthetized with pentobarbital after stimulation of non-shivering thermogenesis by norepinephrine. While in wild-type mice [F]FDG uptake in BAT increased significantly with norepinephrine stimulation of BAT, there was no consistent change in [F]FDG uptake in BAT of mice lacking UCP1.

CONCLUSIONS

[F]FDG uptake within adrenergically stimulated BAT of wild-type and UCP1-knockout mice can significantly vary such that an [F]FDG uptake threshold cannot be used to differentiate wild-type from UCP1-knockout mice. However, while an increase in BAT [F]FDG uptake during adrenergic stimulation is consistently observed in wild-type mice, in UCP1-knockout mice [F]FDG uptake in BAT seems to be independent of β-adrenergic stimulation of non-shivering thermogenesis.

摘要

背景

棕色脂肪组织(BAT)是在大多数哺乳动物体内发现的一种脂肪组织,它通过一种称为非颤抖性产热的交感过程来帮助调节能量平衡和核心体温。BAT活性通常在[F]FDG正电子发射断层扫描/计算机断层扫描(PET/CT)中检测和量化,并且在肾上腺素能刺激期间BAT中放射性示踪剂的摄取常被用作识别该组织中产热活性的替代指标。BAT产热被认为取决于蛋白质UCP1的表达,但文献中关于有和没有UCP1的小鼠BAT内[F]FDG摄取的结果相互矛盾。动物处理技术的差异,如喂食状态、麻醉类型、BAT刺激类型和雌激素水平,被确定为[F]FDG摄取可能的混杂变量。在本研究中,我们旨在使用一种方案来评估野生型和UCP1基因敲除小鼠之间BAT [F]FDG摄取的差异,该方案可最大限度减少因对小鼠处理的不同应激反应而导致的BAT刺激的可能变化。

结果

在用去甲肾上腺素刺激非颤抖性产热后,对用戊巴比妥麻醉的小鼠进行了[F]FDG PET/CT扫描。在野生型小鼠中,随着BAT受到去甲肾上腺素刺激,BAT中[F]FDG摄取显著增加,而在缺乏UCP1的小鼠BAT中,[F]FDG摄取没有一致的变化。

结论

野生型和UCP1基因敲除小鼠在肾上腺素能刺激的BAT内[F]FDG摄取可能有显著差异,以至于不能用[F]FDG摄取阈值来区分野生型和UCP1基因敲除小鼠。然而,虽然在野生型小鼠中始终观察到肾上腺素能刺激期间BAT [F]FDG摄取增加,但在UCP1基因敲除小鼠中,BAT中[F]FDG摄取似乎与非颤抖性产热的β-肾上腺素能刺激无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1636/7648812/f6afa4abcccb/13550_2020_726_Fig1_HTML.jpg

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