Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, 615 Charles E. Young Drive East, Los Angeles, CA 90095, USA.
Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, 149, 13(th) Street, Charlestown, MA 02129, USA.
Cell Rep. 2018 Dec 4;25(10):2919-2934.e8. doi: 10.1016/j.celrep.2018.11.041.
It is well understood that fatty acids can be synthesized, imported, and modified to meet requisite demands in cells. However, following the movement of fatty acids through the multiplicity of these metabolic steps has remained difficult. To better address this problem, we developed Fatty Acid Source Analysis (FASA), a model that defines the contribution of synthesis, import, and elongation pathways to fatty acid homeostasis in saturated, monounsaturated, and polyunsaturated fatty acid pools. Application of FASA demonstrated that elongation can be a major contributor to cellular fatty acid content and showed that distinct pro-inflammatory stimuli (e.g., Toll-like receptors 2, 3, or 4) specifically reprogram homeostasis of fatty acids by differential utilization of synthetic and elongation pathways in macrophages. In sum, this modeling approach significantly advances our ability to interrogate cellular fatty acid metabolism and provides insight into how cells dynamically reshape their lipidomes in response to metabolic or inflammatory signals.
众所周知，脂肪酸可以通过合成、输入和修饰来满足细胞的必需需求。然而，跟踪脂肪酸在这些代谢步骤中的多重变化一直很困难。为了更好地解决这个问题，我们开发了脂肪酸来源分析（Fatty Acid Source Analysis，FASA），这是一种模型，用于定义合成、输入和延伸途径对饱和、单不饱和和多不饱和脂肪酸库中脂肪酸动态平衡的贡献。FASA 的应用表明延伸可以是细胞脂肪酸含量的主要贡献者，并表明不同的促炎刺激物（例如，Toll 样受体 2、3 或 4）通过在巨噬细胞中差异利用合成和延伸途径，特异性地重新编程脂肪酸的动态平衡。总之，这种建模方法显著提高了我们研究细胞脂肪酸代谢的能力，并深入了解了细胞如何响应代谢或炎症信号动态重塑其脂类组。
