Noninvasive evaluation of fat-carbohydrate metabolic switching in heart and contracting skeletal muscle.
Noninvasive evaluation of fat-carbohydrate metabolic switching in heart and contracting skeletal muscle.
复制标题
心脏和收缩骨骼肌中脂肪-碳水化合物代谢转换的无创评估。
DOI：
10.1152/ajpendo.00323.2018
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Wang,Shuyan
中科院分区：
文献类型：
--
作者：
DeGrado,TimothyR;Pandey,MukeshK;Belanger,AnthonyP;Basuli,Falguni;Bansal,Aditya;Wang,Shuyan
心脏和骨骼肌(SM)在脂肪和碳水化合物氧化之间的转换能力是代谢性疾病和运动生理学研究的热点。葡萄糖类似物2-[18F]氟-2-脱氧葡萄糖(18F-FDG)的正电子发射断层扫描(PET)提供了一种非侵入性的定量葡萄糖代谢率的手段。然而，由于缺乏合适的粮农组织探针，PET对脂肪酸氧化(FAO)速率的评估一直受到限制。我们开发了一种代谢捕捉型油酸盐类似物，(Z)-18-[18F]氟-4-硫代-八碳-9-烯酸(18F-FTO)，并研究了用18F-FTO和18F-FDG分别测定大鼠心脏和SM中FAO和葡萄糖摄取的可行性。为了提高SM的代谢率，在注射放射性示踪剂前和注射后30min，分别电刺激禁食大鼠股外侧肌(VL)30min。用肉碱棕榈酰转移酶-1(Cpt-1)抑制剂2-[5-(4-chlorophenyl)-pentyl]oxirane-2-carboxylate钠(POCA)预先处理大鼠，观察放射性示踪剂摄取模式对粮农组织药理抑制的反应。小动物的PET图像和18F-FTO和18F-FDG的生物分布数据分别表明，对照组和CPT-1抑制的大鼠心肌能量供应从外源脂肪酸到葡萄糖的深刻代谢转换。未受刺激的SM对两种示踪剂的摄取均较低。在刺激的VL肌肉中，18F-FTO和18F-FDG的摄取分别增加了4.4倍和28倍，而CPT-1的抑制只影响了18F-FTO的摄取(减少了66%)。18F-FTO是一种依赖于FAO的PET探针，可以与18F-FDG和其他代谢探针一起评估能量底物代谢转换。
The ability of heart and skeletal muscle (SM) to switch between fat and carbohydrate oxidation is of high interest in the study of metabolic diseases and exercise physiology. Positron emission tomography (PET) imaging with the glucose analog 2-[18F]fluoro-2-deoxy-glucose (18F-FDG) provides a noninvasive means to quantitate glucose metabolic rates. However, evaluation of fatty acid oxidation (FAO) rates by PET has been limited by the lack of a suitable FAO probe. We have developed a metabolically trapped oleate analog, (Z)-18-[18F]fluoro-4-thia-octadec-9-enoate (18F-FTO), and investigated the feasibility of using18F-FTO and18F-FDG to measure FAO and glucose uptake, respectively, in heart and SM of rats in vivo. To enhance the metabolic rates in SM, the vastus lateralis (VL) muscle was electrically stimulated in fasted rats for 30 min before and 30 min following radiotracer injection. The responses of radiotracer uptake patterns to pharmacological inhibition of FAO were assessed by pretreatment of the rats with the carnitine palmitoyl-transferase-1 (CPT-1) inhibitor sodium 2-[5-(4-chlorophenyl)-pentyl]oxirane-2-carboxylate (POCA). Small-animal PET images and biodistribution data with18F-FTO and18F-FDG demonstrated profound metabolic switching for energy provision in the myocardium from exogenous fatty acids to glucose in control and CPT-1-inhibited rats, respectively. Uptake of both radiotracers was low in unstimulated SM. In stimulated VL muscle,18F-FTO and18F-FDG uptakes were increased 4.4- and 28-fold, respectively, and CPT-1 inhibition only affected18F-FTO uptake (66% decrease).18F-FTO is a FAO-dependent PET probe that may allow assessment of energy substrate metabolic switching in conjunction with18F-FDG and other metabolic probes.