PMID- 31991095
OWN - NLM
STAT- MEDLINE
DCOM- 20210701
LR  - 20210701
IS  - 2451-9448 (Electronic)
IS  - 2451-9456 (Print)
IS  - 2451-9448 (Linking)
VI  - 27
IP  - 3
DP  - 2020 Mar 19
TI  - DAGL-Beta Functions as a PUFA-Specific Triacylglycerol Lipase in Macrophages.
PG  - 314-321.e5
LID - S2451-9456(20)30005-2 [pii]
LID - 10.1016/j.chembiol.2020.01.005 [doi]
AB  - 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 (DAGLbeta) in macrophages. We demonstrate 
      that DAGLbeta but not DAGLalpha is expressed and active in bone marrow-derived 
      macrophages (BMDMs) as determined by activity-based protein profiling analysis of 
      SILAC BMDMs. Genetic disruption of DAGLbeta 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 DAGLbeta-selective 
      inhibitor. Biochemical assays with synthetic substrates confirm PUFA-TAGs as 
      authentic DAGLbeta substrates. In summary, our findings identify DAGLbeta as a 
      PUFA-specific TAG lipase in primary macrophages.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Shin, Myungsun
AU  - Shin M
AD  - Department of Chemistry, University of Virginia, McCormick Road, PO Box 400319, 
      Charlottesville, VA 22904, USA.
FAU - Ware, Timothy B
AU  - Ware TB
AD  - Department of Chemistry, University of Virginia, McCormick Road, PO Box 400319, 
      Charlottesville, VA 22904, USA.
FAU - Hsu, Ku-Lung
AU  - Hsu KL
AD  - 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. Electronic address: 
      kenhsu@virginia.edu.
LA  - eng
GR  - K99 DA035864/DA/NIDA NIH HHS/United States
GR  - R00 DA035864/DA/NIDA NIH HHS/United States
GR  - R01 DA043571/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200127
PL  - United States
TA  - Cell Chem Biol
JT  - Cell chemical biology
JID - 101676030
RN  - 0 (Fatty Acids, Unsaturated)
RN  - EC 3.1.1.3 (Lipase)
RN  - EC 3.1.1.34 (Lipoprotein Lipase)
RN  - EC 3.1.1.34 (diacylglycerol lipase beta, mouse)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Chromatography, Liquid
MH  - Fatty Acids, Unsaturated/chemistry/*metabolism
MH  - Lipase/chemistry/*metabolism
MH  - Lipoprotein Lipase/chemistry/*metabolism
MH  - Macrophages/*metabolism
MH  - Mass Spectrometry
MH  - Metabolomics
MH  - Mice
PMC - PMC7093258
MID - NIHMS1553378
OTO - NOTNLM
OT  - 2-arachidonoylglycerol
OT  - TAG lipase
OT  - activity-based protein profiling
OT  - adipose triglyceride
OT  - chemical proteomics
OT  - diacylglycerol
OT  - diacylglycerol lipase
OT  - endocannabinoid
OT  - inflammation
OT  - lipidomics
OT  - lipolysis
OT  - macrophage
OT  - triglyceride
COIS- Declaration of Interests The authors declare no competing interests.
EDAT- 2020/01/29 06:00
MHDA- 2021/07/02 06:00
PMCR- 2021/03/19
CRDT- 2020/01/29 06:00
PHST- 2019/09/23 00:00 [received]
PHST- 2019/11/19 00:00 [revised]
PHST- 2020/01/04 00:00 [accepted]
PHST- 2020/01/29 06:00 [pubmed]
PHST- 2021/07/02 06:00 [medline]
PHST- 2020/01/29 06:00 [entrez]
PHST- 2021/03/19 00:00 [pmc-release]
AID - S2451-9456(20)30005-2 [pii]
AID - 10.1016/j.chembiol.2020.01.005 [doi]
PST - ppublish
SO  - Cell Chem Biol. 2020 Mar 19;27(3):314-321.e5. doi: 
      10.1016/j.chembiol.2020.01.005. Epub 2020 Jan 27.