Research Article
LPGAT1 controls the stearate/palmitate ratio of phosphatidylethanolamine and phosphatidylcholine in sn-1 specific remodeling

https://doi.org/10.1016/j.jbc.2022.101685Get rights and content
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Most mammalian phospholipids contain a saturated fatty acid at the sn-1 carbon atom and an unsaturated fatty acid at the sn-2 carbon atom of the glycerol backbone group. While the sn-2 linked chains undergo extensive remodeling by deacylation and reacylation (Lands cycle), it is not known how the composition of saturated fatty acids is controlled at the sn-1 position. Here, we demonstrate that lysophosphatidylglycerol acyltransferase 1 (LPGAT1) is an sn-1 specific acyltransferase that controls the stearate/palmitate ratio of phosphatidylethanolamine (PE) and phosphatidylcholine. Bacterially expressed murine LPGAT1 transferred saturated acyl-CoAs specifically into the sn-1 position of lysophosphatidylethanolamine (LPE) rather than lysophosphatidylglycerol and preferred stearoyl-CoA over palmitoyl-CoA as the substrate. In addition, genetic ablation of LPGAT1 in mice abolished 1-LPE:stearoyl-CoA acyltransferase activity and caused a shift from stearate to palmitate species in PE, dimethyl-PE, and phosphatidylcholine. Lysophosphatidylglycerol acyltransferase 1 KO mice were leaner and had a shorter life span than their littermate controls. Finally, we show that total lipid synthesis was reduced in isolated hepatocytes of LPGAT1 knockout mice. Thus, we conclude that LPGAT1 is an sn-1 specific LPE acyltransferase that controls the stearate/palmitate homeostasis of PE and the metabolites of the PE methylation pathway and that LPGAT1 plays a central role in the regulation of lipid biosynthesis with implications for body fat content and longevity.

Keywords

acyltransferase
metabolism
molecular species
obesity
phospholipid

Abbreviations

CL
cardiolipin
dMePE
dimethylphosphatidylethanolamine
FBS
fetal bovine serum
LC-ESI-MS/MS
liquid chromatography electrospray-ionization tandem mass spectrometry
LPC
lysophosphatidylcholine
LPE
lysophosphatidylethanolamine
LPG
lysophosphatidylglycerol
LPGAT1
lysophosphatidylglycerol acyltransferase 1
MG
monoglyceride
PA
phosphatidic acid
PC
phosphatidylcholine
PE
phosphatidylethanolamine
PEMT
PE methyltransferase
PG
phospatidylglycerol
PI
phosphatidylinositol
TG
triglyceride

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