Faculty of Biology, Department of Animal Physiology, Philipps-Universität Marburg, 35043 Marburg, Germany.
J Lipid Res. 2014 Mar;55(3):398-409. doi: 10.1194/jlr.M042895. Epub 2013 Dec 16.
We used noninvasive magnetic resonance imaging (MRI) and magnetic resonance spectroscopy to compare interscapular brown adipose tissue (iBAT) of wild-type (WT) and uncoupling protein 1 (UCP1)-knockout mice lacking UCP1-mediated nonshivering thermogenesis (NST). Mice were sequentially acclimated to an ambient temperature of 30°C, 18°C, and 5°C. We detected a remodeling of iBAT and a decrease in its lipid content in all mice during cold exposure. Ratios of energy-rich phosphates (ATP/ADP, phosphocreatine/ATP) in iBAT were maintained stable during noradrenergic stimulation of thermogenesis in cold- and warm-adapted mice and no difference between the genotypes was observed. As free fatty acids (FFAs) serve as fuel for thermogenesis and activate UCP1 for uncoupling of oxidative phosphorylation, brown adipose tissue is considered to be a main acceptor and consumer of FFAs. We measured a major loss of FFAs from iBAT during noradrenergic stimulation of thermogenesis. This mobilization of FFAs was observed in iBAT of WT mice as well as in mice lacking UCP1. The high turnover and the release of FFAs from iBAT suggests an enhancement of lipid metabolism, which in itself contributes to the sympathetically activated NST and which is independent from uncoupled respiration mediated by UCP1. Our study demonstrates that MRI, besides its potential for visualizing and quantification of fat tissue, is a valuable tool for monitoring functional in vivo processes like lipid and phosphate metabolism during NST.
我们使用非侵入性磁共振成像(MRI)和磁共振波谱来比较野生型(WT)和解偶联蛋白 1(UCP1)敲除小鼠的肩胛间棕色脂肪组织(iBAT),这些小鼠缺乏 UCP1 介导的非颤抖性产热(NST)。小鼠依次适应环境温度为 30°C、18°C 和 5°C。我们在冷暴露期间检测到所有小鼠的 iBAT 重塑和脂质含量减少。在冷适应和暖适应小鼠的产热过程中,iBAT 中高能磷酸盐(ATP/ADP、磷酸肌酸/ATP)的比率保持稳定,并且在基因型之间没有观察到差异。由于游离脂肪酸(FFAs)作为产热的燃料,并激活 UCP1 以解偶联氧化磷酸化,因此棕色脂肪组织被认为是 FFAs 的主要接受者和消费者。我们在冷适应小鼠中测量到 iBAT 中游离脂肪酸(FFAs)在去甲肾上腺素刺激产热期间的大量损失。在 WT 小鼠的 iBAT 中以及在缺乏 UCP1 的小鼠中都观察到了这种 FFAs 的动员。iBAT 中 FFAs 的高周转率和释放表明脂质代谢增强,这本身有助于交感神经激活的 NST,并且独立于 UCP1 介导的解偶联呼吸。我们的研究表明,MRI 除了具有可视化和量化脂肪组织的潜力外,还是监测 NST 期间脂质和磷酸盐代谢等体内功能过程的有价值工具。