Acsl1 is essential for skin barrier function through the activation of linoleic acid and biosynthesis of ω-O-acylceramide in mice.
Biochim Biophys Acta Mol Cell Biol Lipids
; 1867(2): 159085, 2022 02.
Article
em En
| MEDLINE
| ID: mdl-34813948
ABSTRACT
The long-chain acyl-CoA synthase1 (Acsl1) is a major enzyme that converts long-chain fatty acids to acyl-CoAs. The role of Acsl1 in energy metabolism has been elucidated in the adipose tissue, heart, and skeletal muscle. Here, we demonstrate that systemic deficiency of Acsl1 caused severe skin barrier defects, leading to embryonic lethality. Acsl1 mRNA and protein are expressed in the Acsl1+/+ epidermis, which are absent in Acsl1-/- mice. In Acsl1-/- mice, epidermal ceramide [EOS] (Cer[EOS]) containing ω-O-esterified linoleic acid, a lipid essential for the skin barrier, was significantly reduced. Conversely, ω-hydroxy ceramide (Cer[OS]), a precursor of Cer[EOS], was increased. Moreover, the levels of triglyceride (TG) species containing linoleic acids were lower in Acsl1-/- mice, whereas those not containing linoleic acid were comparable to Acsl1+/+ mice. As TG is considered to work as a reservoir of linoleic acid for the biosynthesis of Cer[EOS] from Cer[OS], our results suggest that Acsl1 plays an essential role in ω-O-acylceramide synthesis by providing linoleic acid for ω-O-esterification. Therefore, our findings identified a new biological role of Acsl1 as a regulator of the skin barrier.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ácido Linoleico
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Biochim Biophys Acta Mol Cell Biol Lipids
Ano de publicação:
2022
Tipo de documento:
Article