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FAHFAs are detected in postprandial chylomicron and VLDL fractions and can be released from TG estolides by LPL in vitro
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DOI：10.1016/j.jlr.2026.101059.png)
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Abstract
En 中文
Fatty acid esters of hydroxy fatty acids (FAHFAs) are bioactive lipids with anti-diabetic and anti-inflammatory effects, but the mechanisms responsible for their transport in blood are not well understood. In this study, we investigated potential serum carriers of FAHFAs. Microscale thermophoresis showed that binding of 9-PAHSA to serum albumin did not support albumin as the dominant carrier under the conditions tested. We therefore turned our attention to lipoproteins and extracellular vesicles, which were isolated from murine serum by density-based ultracentrifugation and characterized by proteomics and lipidomics. Lipidomic analysis revealed that chylomicrons, very-low-density lipoproteins (VLDL), and low-density lipoproteins (LDL) contain both FAHFAs and their storage form, triacylglycerol estolides (TG-EST). In contrast, no FAHFA-containing lipids were detected in serum extracellular vesicles. As a validation case study, we confirmed the presence of TG-EST in postprandial chylomicrons from human volunteers. Functional assays further showed that lipoprotein lipase (LPL), the enzyme that hydrolyzes triacylglycerols during lipoprotein metabolism, releases FAHFAs from TG-EST. LPL exhibited positional selectivity, releasing distinct PAHSA regioisomers with different efficiencies. Together, these results support the interpretation that FAHFA-related lipids are associated with chylomicron, VLDL, and LDL fractions in the postprandial setting and establish LPL-mediated lipolysis as a potential mechanism for the release and distribution of these bioactive lipids in the circulation.
Keywords:
Fatty acid/Transport
VLDL
Lipoproteins
Lipidomics
Lipase
Apo
apolipoprotein
ATGL
adipose triglyceride lipase
AU
arbitrary unit
BSA
bovine serum albumin
CE
cholesteryl ester
Chol
cholesterol
DCM
dichlormethane
DG-EST
diacylglycerol estolide
ER
endoplasmic reticulum
EV
extracellular vesicle
FA
fatty acid
FAHFA
fatty acid ester of hydroxy fatty acid
HDL
high-density lipoprotein
HFD
high-fat diet
LA
linoleic acid
LC-MS
liquid chromatography - mass spectrometry
LDL
low-density lipoprotein
LPL
lipoprotein lipase
MG-EST
monoacylglycerol estolide
MST
microscale thermophoresis
PA
palmitic acid
PAHSA
palmitic acid ester of hydroxystearic acid
PC
phosphatidylcholine
PE
phosphatidylethanolamine
PI
phosphatidylinositol
PL
phospholipids
SM
sphingomyelin
TG
triacylglycerol
TG-EST
triacylglycerol estolide
VLDL
very low-density lipoprotein
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