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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Vydáno v:	Biochimica et biophysica acta. Molecular and cell biology of lipids Ročník 1866; číslo 1; s. 158842
Hlavní autoři:	Tanno, Honoka, Sassa, Takayuki, Sawai, Megumi, Kihara, Akio
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Netherlands Elsevier B.V 01.01.2021
Témata:	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
On-line přístup:	Získat plný text
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Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1388-1981 1879-2618 1879-2618
DOI:	10.1016/j.bbalip.2020.158842