Animal NE2

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Last modified date
  • August 20, 2022
Creator
  • Garside, John C
    • ORCID: 0000-0001-8917-5007
    • Affiliation: College of Arts and Sciences, Department of Physics and Astronomy
    • Other Affiliation: Biomedical Research Imaging Center
Abstract
  • 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.
Methodology
  • In vivo CTA studies were performed on six C57 male mice using a microCT scanner, Quantum GX2 system (Perkin Elmer, Waltham, Massachusetts). The mice were first sedated with an intraperitoneal injection of 70 mg/kg pentobarbital, and an initial CT scan was performed. The CT imaging parameters were 90 kVp of peak voltage, 88 µA of current, standard resolution with 120 µm nominal resolution, 41 mm FOV for one bed acquisition. Then, the mice were intravenously injected with 100 µL of 200 mg/ml solution of Mvivo blood pool contrast agent (MediLumine, Quebec, Canada). The Mvivo contrast agent is a relatively new gold-nanoparticle based blood pool contrast agent with core particle size of 15 nm. Compared to the other gold nanoparticle based contrast agent, Aurovist, Mvivo showed much longer circulation time with similar enhancement power (data not shown). At 5 min after the injection of Mvivo, a second CT scan was performed. The mice were then either injected subcutaneously with norepinephrine (n=3, 1 mg/kg, subcutaneous) or CL-316,243 (n=3, 1 mg/kg, subcutaneous), and a third CT scan was performed at ten minutes post injection. Finally, the mice were euthanized with an overdose of pentobarbital (200mg/kg), and a high-resolution postmortem scan was performed with 40 µm isotropic nominal resolution to be achieved in the region of iBAT.
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  • 3D
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  • Dataset
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  • In Copyright
License
  • CC0 1.0 Universal
Language
  • English

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