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.
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Authors | Honoka Tanno, Takayuki Sassa, Megumi Sawai, Akio Kihara |
Journal | Biochimica et biophysica acta. Molecular and cell biology of lipids
(Biochim Biophys Acta Mol Cell Biol Lipids)
Vol. 1866
Issue 1
Pg. 158842
(01 2021)
ISSN: 1879-2618 [Electronic] Netherlands |
PMID | 33069870
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2020 Elsevier B.V. All rights reserved. |
Chemical References |
- Acyl Coenzyme A
- Amino Acids, Branched-Chain
- Ceramides
- Cholesterol Esters
- Elovl1 protein, mouse
- Elovl3 protein, mouse
- Elovl7 protein, mouse
- Aldehyde Oxidoreductases
- FAR1 protein, mouse
- AWAT2 protein, mouse
- Acyltransferases
- Fatty Acid Elongases
- Sterol O-Acyltransferase
- sterol O-acyltransferase 1
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Topics |
- Acyl Coenzyme A
(metabolism)
- Acyltransferases
(genetics, metabolism)
- Aldehyde Oxidoreductases
(genetics, metabolism)
- Amino Acids, Branched-Chain
(classification, metabolism)
- Animals
- Ceramides
(classification, metabolism)
- Cholesterol Esters
(classification, metabolism)
- Fatty Acid Elongases
(genetics, metabolism)
- Gene Expression Regulation
- HEK293 Cells
- Humans
- Lipidomics
(methods)
- Liver
(metabolism)
- Male
- Meibomian Glands
(metabolism)
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Skin
(metabolism)
- Sterol O-Acyltransferase
(genetics, metabolism)
- Substrate Specificity
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