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

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.
AuthorsHonoka Tanno, Takayuki Sassa, Megumi Sawai, Akio Kihara
JournalBiochimica 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
PMID33069870 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 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
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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