Metabolomics

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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. 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.

INSTRUMENT(S): Direct infusion MS - positive, Direct infusion MS - negative

SUBMITTER: Meei-Hua Lin  

PROVIDER: MTBLS1138 | MetaboLights | 2021-07-15

REPOSITORIES: MetaboLights

Dataset's files

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Action DRS
MTBLS1138 Other
1Oacylcer 15769-1-011018-4_1.raw Raw
1Oacylcer 16018-5-030215-3_1.raw Raw
1Oacylcer 16657-1-022015-1-o-acyl_1.raw Raw
1Oacylcer 16657-2-022015-3-o-acyl_1.raw Raw
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Fatty acid transport protein 4 is required for incorporation of saturated ultralong-chain fatty acids into epidermal ceramides and monoacylglycerols.

Lin Meei-Hua MH   Hsu Fong-Fu FF   Crumrine Debra D   Meyer Jason J   Elias Peter M PM   Miner Jeffrey H JH  

Scientific reports 20190913 1


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<sup>-/-</sup> mice die neonatally from a defective barrier. Here we used electron microscopy and lipidomics to characterize defects in Fatp4<sup>-/-</sup> mice. Mutants showed lamellar body, corneocyte lipid envelope, and cornified envelope abnormalities. Lipid  ...[more]

Publication: 1/5

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