Production of branched-chain very-long-chain fatty acids by fatty acid elongases and their tissue distribution in mammals

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 li...

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Published in:Biochimica et biophysica acta. Molecular and cell biology of lipids Vol. 1866; no. 1; p. 158842
Main Authors: Tanno, Honoka, Sassa, Takayuki, Sawai, Megumi, Kihara, Akio
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01.01.2021
Subjects:
Acyl Coenzyme A - metabolism
Acyltransferases - genetics
Acyltransferases - metabolism
Aldehyde Oxidoreductases - genetics
Aldehyde Oxidoreductases - metabolism
Amino Acids, Branched-Chain - classification
Amino Acids, Branched-Chain - metabolism
Animals
Branched-chain fatty acid
Ceramide
ceramides
Ceramides - classification
Ceramides - metabolism
Cholesterol Esters - classification
Cholesterol Esters - metabolism
Cholesteryl ester
eyes
fatty acid elongase
Fatty Acid Elongases - genetics
Fatty Acid Elongases - metabolism
Gene Expression Regulation
HEK293 Cells
Humans
isozymes
Lipidomics - methods
liquid chromatography
liver
Liver - metabolism
Male
Meibomian gland
Meibomian Glands - metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
mutants
Skin - metabolism
Sterol O-Acyltransferase - genetics
Sterol O-Acyltransferase - metabolism
Substrate Specificity
tandem mass spectrometry
tissue distribution
Very-long-chain fatty acid
Wax ester
Crat
MS
Tg-Elovl1
SOAT
TLC
MGD
MS/MS
VLC
Meibomian gland
ELOVL
FAl
TFLL
FAR
AWAT
LC
Ceramide
Branched-chain fatty acid
Very-long-chain fatty acid
Cholesteryl ester
FA
Wax ester
IVL
ISSN:1388-1981, 1879-2618, 1879-2618
Online Access:Get full text
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Summary: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. [Display omitted] •Saturated branched-chain fatty acids are elongated by ELOVL1, ELOVL3, and ELOVL7.•ELOVL1 produces very-long-chain branched-chain fatty acids in the meibomian glands.•Branched-chain fatty acids are incorporated into ceramides.•Branched-chain ceramides are present in the meibomian glands and liver.
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ISSN:1388-1981
1879-2618
1879-2618
DOI:10.1016/j.bbalip.2020.158842