Department of Internal Medicine and Endocrinology, Aarhus University Hospital, 8200 Aarhus N, Denmark.
Institute of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark.
Int J Mol Sci. 2018 Sep 1;19(9):2597. doi: 10.3390/ijms19092597.
The capacity to increase energy expenditure makes brown adipose tissue (BAT) a putative target for treatment of metabolic diseases such as obesity. Presently, investigation of BAT in vivo is mainly performed by fluoro-d-glucose positron emission tomography (FDG PET)/CT. However, non-radioactive methods that add information on, for example, substrate metabolism are warranted. Thus, the aim of this study was to evaluate the potential of hyperpolarized [1-C]pyruvate Magnetic Resonance Imaging (HP-MRI) to determine BAT activity in mice following chronic cold exposure. Cold (6 °C) and thermo-neutral (30 °C) acclimated mice were scanned with HP-MRI for assessment of the interscapular BAT (iBAT) activity. Comparable mice were scanned with the conventional method FDG PET/MRI. Finally, iBAT was evaluated for gene expression and protein levels of the specific thermogenic marker, uncoupling protein 1 (UCP1). Cold exposure increased the thermogenic capacity 3⁻4 fold ( < 0.05) as measured by gene and protein analysis. Furthermore, cold exposure as compared with thermo-neutrality increased iBAT pyruvate metabolism by 5.5-fold determined by HP-MRI which is in good agreement with the 5-fold increment in FDG uptake ( < 0.05) measured by FDG PET/MRI. iBAT activity is detectable in mice using HP-MRI in which potential changes in intracellular metabolism may add useful information to the conventional FDG PET studies. HP-MRI may also be a promising radiation-free tool for repetitive BAT studies in humans.
棕色脂肪组织(BAT)具有增加能量消耗的能力,使其成为治疗肥胖等代谢性疾病的潜在靶点。目前,体内 BAT 的研究主要通过氟代葡萄糖正电子发射断层扫描(FDG PET)/CT 进行。然而,需要添加关于代谢等信息的非放射性方法。因此,本研究旨在评估超极化 [1-C] 丙酮酸磁共振成像(HP-MRI)在慢性冷暴露后确定小鼠 BAT 活性的潜力。将冷(6°C)和热中性(30°C)驯化的小鼠用 HP-MRI 扫描,以评估肩胛间 BAT(iBAT)的活性。用常规方法 FDG PET/MRI 扫描可比的小鼠。最后,评估 iBAT 的特定生热标志物解偶联蛋白 1(UCP1)的基因表达和蛋白水平。基因和蛋白分析表明,冷暴露使产热能力增加了 3-4 倍(<0.05)。与热中性相比,冷暴露使 iBAT 丙酮酸代谢增加了 5.5 倍,这与 FDG PET/MRI 测量的 FDG 摄取增加 5 倍(<0.05)一致。使用 HP-MRI 可以在小鼠中检测到 BAT 活性,其中细胞内代谢的潜在变化可能会为传统的 FDG PET 研究提供有用的信息。HP-MRI 也可能是一种有前途的无辐射工具,可用于人类重复性 BAT 研究。