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Production of branched-chain very-long-chain fatty acids by fatty acid elongases and their tissue distribution in mammals
- Source :
- Biochimica et biophysica acta. Molecular and cell biology of lipids. 1866(1)
- Publication Year :
- 2020
-
Abstract
- Although most mammalian fatty acids (FAs) are straight-chain, there also exist branched-chain FAs such as iso- and anteiso-FAs, especially in the meibomian glands. Meibum lipids, which are secreted from the meibomian glands and are important for dry eye prevention, contain abundant branched-chain lipids, such as cholesteryl esters and wax esters with chain-lengths of ≥C21 (very-long-chain; VLC). However, the exact tissue distribution of branched-chain lipids or the enzymes involved in the production of branched-chain VLCFAs has remained poorly understood. Here, we revealed that FA elongases ELOVL1, ELOVL3, and ELOVL7, of the seven mammalian ELOVL isozymes, elongated saturated branched-chain acyl-CoAs. ELOVL3 was highly active toward iso-C17:0 and anteiso-C17:0 acyl-CoAs and elongated them up to iso-C23:0 and anteiso-C25:0 acyl-CoAs, respectively. ELOVL1 elongated both iso- and anteiso-C23:0 acyl-CoAs to C25:0 acyl-CoAs. By establishing a liquid chromatography-tandem mass spectrometry method capable of separating branched- and straight-chain lipids, we showed that essentially all of the cholesteryl esters and 88% of the wax esters in the mouse meibomian glands are branched. In Elovl1 mutant mice, the levels of ≥C24:0 branched-chain cholesteryl esters and ≥C25:0 branched-chain wax esters were decreased, indicating that ELOVL1 indeed elongates branched-chain VLC acyl-CoAs in vivo. In addition, substantial amounts of ceramides containing branched-chain FAs were present in the skin, meibomian glands, and liver. Our findings provide new insights into the molecular mechanisms that create FA and lipid diversity.
- Subjects :
- 0301 basic medicine
Male
Ceramide
Fatty Acid Elongases
Very long chain fatty acid
Meibomian gland
Mice, Transgenic
Ceramides
Isozyme
Substrate Specificity
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
medicine
Animals
Humans
Molecular Biology
Skin
chemistry.chemical_classification
Wax
Meibomian Glands
Cell Biology
Aldehyde Oxidoreductases
Wax ester
Mice, Inbred C57BL
030104 developmental biology
Enzyme
medicine.anatomical_structure
HEK293 Cells
chemistry
Biochemistry
Gene Expression Regulation
Liver
visual_art
Lipidomics
Cholesteryl ester
visual_art.visual_art_medium
lipids (amino acids, peptides, and proteins)
Acyl Coenzyme A
Cholesterol Esters
030217 neurology & neurosurgery
Acyltransferases
Amino Acids, Branched-Chain
Sterol O-Acyltransferase
Subjects
Details
- ISSN :
- 18792618
- Volume :
- 1866
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Biochimica et biophysica acta. Molecular and cell biology of lipids
- Accession number :
- edsair.doi.dedup.....9089b79715bd144f291533eae4516605