PMID- 30523059
OWN - NLM
STAT- MEDLINE
DCOM- 20190904
LR  - 20190904
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 476
IP  - 1
DP  - 2019 Jan 11
TI  - Glycerol-3-phosphate acyltransferases 3 and 4 direct glycerolipid synthesis and 
      affect functionality in activated macrophages.
PG  - 85-99
LID - 10.1042/BCJ20180381 [doi]
AB  - Macrophage classical M1 activation via TLR4 triggers a variety of responses to 
      achieve the elimination of foreign pathogens. During this process, there is also 
      an increase in lipid droplets which contain large quantities of triacylglycerol 
      (TAG) and phospholipid (PL). The functional consequences of this increment in 
      lipid mass are poorly understood. Here, we studied the contribution of 
      glycerolipid synthesis to lipid accumulation, focusing specifically on the first 
      and rate-limiting enzyme of the pathway: glycerol-3-phosphate acyltransferase 
      (GPAT). Using bone marrow-derived macrophages (BMDMs) treated with Kdo(2)-lipid 
      A, we showed that glycerolipid synthesis is induced during macrophage activation. 
      GPAT4 protein level and GPAT3/GPAT4 enzymatic activity increase during this 
      process, and these two isoforms were required for the accumulation of cell TAG 
      and PL. The phagocytic capacity of Gpat3(-/-) and Gpat4(-/-) BMDM was impaired. 
      Additionally, inhibiting fatty acid beta-oxidation reduced phagocytosis only 
      partially, suggesting that lipid accumulation is not necessary for the energy 
      requirements for phagocytosis. Finally, Gpat4(-/-) BMDM expressed and released 
      more pro-inflammatory cytokines and chemokines after macrophage activation, 
      suggesting a role for GPAT4 in suppressing inflammatory responses. Together, 
      these results provide evidence that glycerolipid synthesis directed by GPAT4 is 
      important for the attenuation of the inflammatory response in activated 
      macrophages.
CI  - (c) 2019 The Author(s). Published by Portland Press Limited on behalf of the 
      Biochemical Society.
FAU - Quiroga, Ivana Y
AU  - Quiroga IY
AD  - Instituto de Investigaciones Bioquimicas de La Plata, Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas, Facultad de Ciencias Medicas, Universidad 
      Nacional de La Plata, La Plata 1900, Argentina.
FAU - Pellon-Maison, Magali
AU  - Pellon-Maison M
AD  - Instituto de Investigaciones Bioquimicas de La Plata, Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas, Facultad de Ciencias Medicas, Universidad 
      Nacional de La Plata, La Plata 1900, Argentina.
FAU - Suchanek, Amanda L
AU  - Suchanek AL
AD  - Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599, 
      U.S.A.
FAU - Coleman, Rosalind A
AU  - Coleman RA
AD  - Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599, 
      U.S.A.
FAU - Gonzalez-Baro, Maria R
AU  - Gonzalez-Baro MR
AUID- ORCID: 0000-0002-6778-284X
AD  - Instituto de Investigaciones Bioquimicas de La Plata, Consejo Nacional de 
      Investigaciones Cientificas y Tecnicas, Facultad de Ciencias Medicas, Universidad 
      Nacional de La Plata, La Plata 1900, Argentina mgbaro@med.unlp.edu.ar.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190111
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Phospholipids)
RN  - 0 (Triglycerides)
RN  - EC 2.3.1.15 (GPAT4 protein, mouse)
RN  - EC 2.3.1.15 (Glycerol-3-Phosphate O-Acyltransferase)
RN  - EC 2.3.1.51 (1-Acylglycerol-3-Phosphate O-Acyltransferase)
RN  - EC 2.3.1.51 (GPAT3 protein, mouse)
SB  - IM
MH  - 1-Acylglycerol-3-Phosphate O-Acyltransferase/genetics/*metabolism
MH  - Animals
MH  - Glycerol-3-Phosphate O-Acyltransferase/genetics/*metabolism
MH  - Inflammation/enzymology/genetics/pathology
MH  - *Lipogenesis
MH  - Macrophage Activation/genetics
MH  - Macrophages/*enzymology/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Phospholipids/*biosynthesis/genetics
MH  - Triglycerides/*biosynthesis/genetics
OTO - NOTNLM
OT  - Kdo2-lipid A
OT  - cytokines
OT  - lipid droplet
OT  - phagocytosis
OT  - phospholipid
OT  - triacylglycerol
EDAT- 2018/12/14 06:00
MHDA- 2019/09/05 06:00
CRDT- 2018/12/08 06:00
PHST- 2018/05/21 00:00 [received]
PHST- 2018/12/03 00:00 [revised]
PHST- 2018/12/05 00:00 [accepted]
PHST- 2018/12/14 06:00 [pubmed]
PHST- 2019/09/05 06:00 [medline]
PHST- 2018/12/08 06:00 [entrez]
AID - BCJ20180381 [pii]
AID - 10.1042/BCJ20180381 [doi]
PST - epublish
SO  - Biochem J. 2019 Jan 11;476(1):85-99. doi: 10.1042/BCJ20180381.