Departments of Nutritional Science and Toxicology, University of California Berkeley, Berkeley, California 94720, United States.
ACS Chem Biol. 2012 Nov 16;7(11):1884-91. doi: 10.1021/cb300194b. Epub 2012 Sep 6.
Detection and quantification of fatty acid fluxes in animal model systems following physiological, pathological, or pharmacological challenges is key to our understanding of complex metabolic networks as these macronutrients also activate transcription factors and modulate signaling cascades including insulin sensitivity. To enable noninvasive, real-time, spatiotemporal quantitative imaging of fatty acid fluxes in animals, we created a bioactivatable molecular imaging probe based on long-chain fatty acids conjugated to a reporter molecule (luciferin). We show that this probe faithfully recapitulates cellular fatty acid uptake and can be used in animal systems as a valuable tool to localize and quantitate in real time lipid fluxes such as intestinal fatty acid absorption and brown adipose tissue activation. This imaging approach should further our understanding of basic metabolic processes and pathological alterations in multiple disease models.
在生理、病理或药理学挑战后,检测和定量动物模型系统中的脂肪酸通量对于我们理解复杂代谢网络至关重要,因为这些宏量营养素还能激活转录因子并调节信号级联反应,包括胰岛素敏感性。为了实现对动物体内脂肪酸通量的非侵入性、实时、时空定量成像,我们基于与报告分子(荧光素)连接的长链脂肪酸,创建了一种可激活的分子成像探针。我们证明,该探针忠实地再现了细胞脂肪酸摄取,并可在动物系统中作为一种有价值的工具,用于实时定位和定量脂质通量,如肠道脂肪酸吸收和棕色脂肪组织激活。这种成像方法应该有助于我们理解多种疾病模型中的基本代谢过程和病理改变。