title: Impaired epidermal permeability barrier in mice lacking elovl1, the gene responsible for very-long-chain fatty acid production.
abstract: The sphingolipid backbone ceramide (Cer) is a major component of lipid lamellae in the stratum corneum of epidermis and has a pivotal role in epidermal barrier formation. Unlike Cers in other tissues, Cers in epidermis contain extremely long fatty acids (FAs). Decreases in epidermal Cer levels, as well as changes in their FA chain lengths, cause several cutaneous disorders. However, the molecular mechanisms that produce such extremely long Cers and determine their chain lengths are poorly understood. We generated mice deficient in the Elovl1 gene, which encodes the FA elongase responsible for producing C20 to C28 FAs. Elovl1 knockout mice died shortly after birth due to epidermal barrier defects. The lipid lamellae in the stratum corneum were largely diminished in these mice. In the epidermis of the Elovl1-null mice, the levels of Cers with ≥C26 FAs were decreased, while those of Cers with ≤C24 FAs were increased. In contrast, the levels of C24 sphingomyelin were reduced, accompanied by an increase in C20 sphingomyelin levels. Two ceramide synthases, CerS2 and CerS3, expressed in an epidermal layer-specific manner, regulate Elovl1 to produce acyl coenzyme As with different chain lengths. Elovl1 is a key determinant of epidermal Cer chain length and is essential for permeability barrier formation.
authors.affiliation: Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sassa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ohno
authors.forename: Shotaro
authors.initials: S
authors.lastname: Suzuki
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Nomura
authors.forename: Chieko
authors.initials: C
authors.lastname: Nishioka
authors.forename: Toshiki
authors.initials: T
authors.lastname: Kashiwagi
authors.forename: Taisuke
authors.initials: T
authors.lastname: Hirayama
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
authors.forename: Ryo
authors.initials: R
authors.lastname: Taguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: Akio
authors.initials: A
authors.lastname: Kihara
mesh_terms: D000123:Acetyltransferases / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D002518:Ceramides / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D004817:Epidermis / Q000002:abnormalities / Q000201:enzymology* / Q000473:pathology; D000081031:Fatty Acid Elongases; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005804:Genes, Lethal; D057809:HEK293 Cells; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010539:Permeability; D051049:Sphingosine N-Acyltransferase / Q000378:metabolism
chemical_list: D002518:Ceramides; C000630949:ELOVL1 protein, human; D005227:Fatty Acids; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; C513562:CerS3 protein, mouse; C580723:Cers2 protein, mouse; D051049:Sphingosine N-Acyltransferase