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DAGL-Beta Functions as a PUFA-Specific Triacylglycerol Lipase in Macrophages.

Authors: Shin, Myungsun  Ware, Timothy B  Hsu, Ku-Lung 
Citation: Shin M, etal., Cell Chem Biol. 2020 Mar 19;27(3):314-321.e5. doi: 10.1016/j.chembiol.2020.01.005. Epub 2020 Jan 27.
Pubmed: (View Article at PubMed) PMID:31991095
DOI: Full-text: DOI:10.1016/j.chembiol.2020.01.005

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.


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RGD Object Information
RGD ID: 25671402
Created: 2020-04-25
Species: All species
Last Modified: 2020-04-25
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.