In vivo imaging of brown adipose tissue vasculature reactivity during adrenergic stimulation of non-shivering thermogenesis in mice.

In vivo imaging of brown adipose tissue vasculature reactivity during adrenergic stimulation of non-shivering thermogenesis in mice.
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DOI:
10.1038/s41598-022-25819-6
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发表时间:
2022-12-10
期刊:
影响因子:
4.6
通讯作者:
Branca, Rosa T.
Branca, Rosa T.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Garside, John C.;Livingston, Eric W.;Frank, Jonathan E.;Yuan, Hong;Branca, Rosa T.

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棕色脂肪组织(BAT)是一种专门用于产热(非颤抖性产热)的脂肪组织,被哺乳动物用于在暴露于寒冷时保护核心体温。几项研究表明,在非颤抖性产热期间,BAT需氧量的增加通过组织血流量的局部和特定增加来满足。虽然BAT的脉管系统已经在啮齿动物中使用组织学、光学和CT成像技术进行了广泛的死后研究,但在非颤抖产热刺激期间的脉管系统变化从未在体内直接检测到。在这里,通过使用具有金纳米颗粒的计算机断层扫描(CT)血管造影术,我们非侵入性地研究了在去甲肾上腺素(一种已知介导棕色脂肪产热的血管收缩剂)和CL 316,243(一种已知也在啮齿动物中引起BAT产热的特异性β3-肾上腺素能激动剂)对非颤抖性产热的肾上腺素能刺激期间BAT血管系统的变化。我们发现,虽然CL 316,243在BAT中引起局部血管舒张,但对全身其他血管系统的影响很小,去甲肾上腺素除了引起外周血管收缩外,还引起局部血管舒张。因此,与CL相比,在注射NE后观察到BAT灌注的显著更大的相对增加。本研究证明了在临床前研究中使用体内CT血管造影作为定性和定量评估BAT血管反应性的有效工具。
Brown adipose tissue (BAT) is a fat tissue specialized in heat production (non-shivering thermogenesis) and used by mammals to defend core body temperature when exposed to cold. Several studies have shown that during non-shivering thermogenesis the increase in BAT oxygen demand is met by a local and specific increase in tissue’s blood flow. While the vasculature of BAT has been extensively studied postmortem in rodents using histology, optical and CT imaging techniques, vasculature changes during stimulation of non-shivering thermogenesis have never been directly detected in vivo. Here, by using computed tomography (CT) angiography with gold nanoparticles we investigate, non-invasively, changes in BAT vasculature during adrenergic stimulation of non-shivering thermogenesis by norepinephrine, a vasoconstrictor known to mediate brown fat heat production, and by CL 316,243, a specific β3-adrenergic agonist also known to elicit BAT thermogenesis in rodents. We found that while CL 316,243 causes local vasodilation in BAT, with little impact on the rest of the vasculature throughout the body, norepinephrine leads to local vasodilation in addition to peripheral vasoconstriction. As a result, a significantly greater relative increase in BAT perfusion is observed following the injection of NE compared to CL. This study demonstrates the use of in vivo CT angiography as an effective tool in assessing vascular reactivity in BAT both qualitatively and quantitatively in preclinical studies.
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发表时间: 2011-02
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