Fatty acid transport protein 4 is required for incorporation of saturated ultralong-chain fatty acids into epidermal ceramides and monoacylglycerols

Abstract Fatty acid transport protein 4 (FATP4) is an acyl-CoA synthetase that is required for normal permeability barrier in mammalian skin. FATP4 (SLC27A4) mutations cause ichthyosis prematurity syndrome, a nonlethal disorder. In contrast, Fatp4 −/− mice die neonatally from a defective barrier. He...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Meei-Hua Lin, Fong-Fu Hsu, Debra Crumrine, Jason Meyer, Peter M. Elias, Jeffrey H. Miner
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dfc7f6f76ecc4c2db8ed01da88b91819
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:dfc7f6f76ecc4c2db8ed01da88b91819
record_format	dspace
spelling	oai:doaj.org-article:dfc7f6f76ecc4c2db8ed01da88b918192021-12-02T16:08:05ZFatty acid transport protein 4 is required for incorporation of saturated ultralong-chain fatty acids into epidermal ceramides and monoacylglycerols10.1038/s41598-019-49684-y2045-2322https://doaj.org/article/dfc7f6f76ecc4c2db8ed01da88b918192019-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-49684-yhttps://doaj.org/toc/2045-2322Abstract Fatty acid transport protein 4 (FATP4) is an acyl-CoA synthetase that is required for normal permeability barrier in mammalian skin. FATP4 (SLC27A4) mutations cause ichthyosis prematurity syndrome, a nonlethal disorder. In contrast, Fatp4 −/− mice die neonatally from a defective barrier. Here we used electron microscopy and lipidomics to characterize defects in Fatp4 −/− mice. Mutants showed lamellar body, corneocyte lipid envelope, and cornified envelope abnormalities. Lipidomics identified two lipids previously speculated to be present in mouse epidermis, sphingosine β-hydroxyceramide and monoacylglycerol; mutants displayed decreased proportions of these and the two ceramide classes that carry ultralong-chain, amide-linked fatty acids (FAs) thought to be critical for barrier function, unbound ω-O-acylceramide and bound ω-hydroxyceramide, the latter constituting the major component of the corneocyte lipid envelope. Other abnormalities included elevated amounts of sphingosine α-hydroxyceramide, phytosphingosine non-hydroxyceramide, and 1-O-acylceramide. Acyl chain length alterations in ceramides also suggested roles for FATP4 in esterifying saturated non-hydroxy and β-hydroxy FAs with at least 25 carbons and saturated or unsaturated ω-hydroxy FAs with at least 30 carbons to CoA. Our lipidomic analysis is the most thorough such study of the Fatp4 −/− mouse skin barrier to date, providing information about how FATP4 can contribute to barrier function by regulating fatty acyl moieties in various barrier lipids.Meei-Hua LinFong-Fu HsuDebra CrumrineJason MeyerPeter M. EliasJeffrey H. MinerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-18 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Meei-Hua Lin Fong-Fu Hsu Debra Crumrine Jason Meyer Peter M. Elias Jeffrey H. Miner Fatty acid transport protein 4 is required for incorporation of saturated ultralong-chain fatty acids into epidermal ceramides and monoacylglycerols
description	Abstract Fatty acid transport protein 4 (FATP4) is an acyl-CoA synthetase that is required for normal permeability barrier in mammalian skin. FATP4 (SLC27A4) mutations cause ichthyosis prematurity syndrome, a nonlethal disorder. In contrast, Fatp4 −/− mice die neonatally from a defective barrier. Here we used electron microscopy and lipidomics to characterize defects in Fatp4 −/− mice. Mutants showed lamellar body, corneocyte lipid envelope, and cornified envelope abnormalities. Lipidomics identified two lipids previously speculated to be present in mouse epidermis, sphingosine β-hydroxyceramide and monoacylglycerol; mutants displayed decreased proportions of these and the two ceramide classes that carry ultralong-chain, amide-linked fatty acids (FAs) thought to be critical for barrier function, unbound ω-O-acylceramide and bound ω-hydroxyceramide, the latter constituting the major component of the corneocyte lipid envelope. Other abnormalities included elevated amounts of sphingosine α-hydroxyceramide, phytosphingosine non-hydroxyceramide, and 1-O-acylceramide. Acyl chain length alterations in ceramides also suggested roles for FATP4 in esterifying saturated non-hydroxy and β-hydroxy FAs with at least 25 carbons and saturated or unsaturated ω-hydroxy FAs with at least 30 carbons to CoA. Our lipidomic analysis is the most thorough such study of the Fatp4 −/− mouse skin barrier to date, providing information about how FATP4 can contribute to barrier function by regulating fatty acyl moieties in various barrier lipids.
format	article
author	Meei-Hua Lin Fong-Fu Hsu Debra Crumrine Jason Meyer Peter M. Elias Jeffrey H. Miner
author_facet	Meei-Hua Lin Fong-Fu Hsu Debra Crumrine Jason Meyer Peter M. Elias Jeffrey H. Miner
author_sort	Meei-Hua Lin
title	Fatty acid transport protein 4 is required for incorporation of saturated ultralong-chain fatty acids into epidermal ceramides and monoacylglycerols
title_short	Fatty acid transport protein 4 is required for incorporation of saturated ultralong-chain fatty acids into epidermal ceramides and monoacylglycerols
title_full	Fatty acid transport protein 4 is required for incorporation of saturated ultralong-chain fatty acids into epidermal ceramides and monoacylglycerols
title_fullStr	Fatty acid transport protein 4 is required for incorporation of saturated ultralong-chain fatty acids into epidermal ceramides and monoacylglycerols
title_full_unstemmed	Fatty acid transport protein 4 is required for incorporation of saturated ultralong-chain fatty acids into epidermal ceramides and monoacylglycerols
title_sort	fatty acid transport protein 4 is required for incorporation of saturated ultralong-chain fatty acids into epidermal ceramides and monoacylglycerols
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/dfc7f6f76ecc4c2db8ed01da88b91819
work_keys_str_mv	AT meeihualin fattyacidtransportprotein4isrequiredforincorporationofsaturatedultralongchainfattyacidsintoepidermalceramidesandmonoacylglycerols AT fongfuhsu fattyacidtransportprotein4isrequiredforincorporationofsaturatedultralongchainfattyacidsintoepidermalceramidesandmonoacylglycerols AT debracrumrine fattyacidtransportprotein4isrequiredforincorporationofsaturatedultralongchainfattyacidsintoepidermalceramidesandmonoacylglycerols AT jasonmeyer fattyacidtransportprotein4isrequiredforincorporationofsaturatedultralongchainfattyacidsintoepidermalceramidesandmonoacylglycerols AT petermelias fattyacidtransportprotein4isrequiredforincorporationofsaturatedultralongchainfattyacidsintoepidermalceramidesandmonoacylglycerols AT jeffreyhminer fattyacidtransportprotein4isrequiredforincorporationofsaturatedultralongchainfattyacidsintoepidermalceramidesandmonoacylglycerols
_version_	1718384624427597824

Fatty acid transport protein 4 is required for incorporation of saturated ultralong-chain fatty acids into epidermal ceramides and monoacylglycerols

Ejemplares similares