二酰甘油脂肪酶-β在巨噬细胞中作为多不饱和脂肪酸特异性三酰甘油脂肪酶发挥作用。
DAGL-Beta Functions as a PUFA-Specific Triacylglycerol Lipase in Macrophages.
作者信息
Shin Myungsun, Ware Timothy B, Hsu Ku-Lung
机构信息
Department of Chemistry, University of Virginia, McCormick Road, PO Box 400319, Charlottesville, VA 22904, USA.
Department of Chemistry, University of Virginia, McCormick Road, PO Box 400319, Charlottesville, VA 22904, USA; Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA; University of Virginia Cancer Center, University of Virginia, Charlottesville, VA 22903, USA.
出版信息
Cell Chem Biol. 2020 Mar 19;27(3):314-321.e5. doi: 10.1016/j.chembiol.2020.01.005. Epub 2020 Jan 27.
Here, we apply quantitative chemical proteomics and untargeted lipidomics to assign a polyunsaturated fatty acid (PUFA)-specific triacylglycerol (TAG) lipase activity for diacylglycerol lipase-beta (DAGLβ) in macrophages. We demonstrate that DAGLβ but not DAGLα is expressed and active in bone marrow-derived macrophages (BMDMs) as determined by activity-based protein profiling analysis of SILAC BMDMs. Genetic disruption of DAGLβ resulted in accumulation of cellular TAGs composed of PUFA but not saturated/low unsaturated fatty acid counterparts, which is recapitulated in wild-type macrophages treated with a DAGLβ-selective inhibitor. Biochemical assays with synthetic substrates confirm PUFA-TAGs as authentic DAGLβ substrates. In summary, our findings identify DAGLβ as a PUFA-specific TAG lipase in primary macrophages.
在此，我们应用定量化学蛋白质组学和非靶向脂质组学来确定巨噬细胞中双酰甘油脂肪酶-β（DAGLβ）的多不饱和脂肪酸（PUFA）特异性三酰甘油（TAG）脂肪酶活性。我们证明，通过对稳定同位素标记（SILAC）的骨髓来源巨噬细胞（BMDM）进行基于活性的蛋白质谱分析确定，DAGLβ而非DAGLα在骨髓来源巨噬细胞（BMDM）中表达且具有活性。DAGLβ的基因破坏导致由PUFA组成的细胞TAG积累，而饱和/低不饱和脂肪酸对应物则不会积累，在用DAGLβ选择性抑制剂处理的野生型巨噬细胞中也观察到了这一现象。用合成底物进行的生化分析证实PUFA-TAG是真正的DAGLβ底物。总之，我们的研究结果确定DAGLβ是原代巨噬细胞中一种PUFA特异性TAG脂肪酶。
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