RRC ID 71974
著者 Otsuka K, Sawai-Ogawa M, Kihara A.
タイトル Formation of fatty alcohols-components of meibum lipids-by the fatty acyl-CoA reductase FAR2 is essential for dry eye prevention.
ジャーナル FASEB J
Abstract Various lipids (mainly meibum lipids secreted by the meibomian glands) are present in the tear film lipid layer and play important roles in tear stability and the health of the cornea and conjunctiva. Many meibum lipids contain fatty alcohols (FAls) with chain lengths ≥C24, but the fatty acyl-CoA reductases (FARs) that produce them remain unclear. Here, using cell-based assays, we found that the two FAR isozymes (FAR1 and FAR2) show different substrate specificities: FAR1 and FAR2 are involved in the production of C16-C18 and ≥C20 FAls, respectively. Next, we generated Far2 knockout (KO) mice and examined their dry eye phenotype and meibum lipid composition. These mice showed a severe dry eye phenotype, characterized by plugged meibomian gland orifices, corneal damage, and tear film instability. The plugging was attributed to an increase in the melting point of the meibum lipids. Liquid chromatography coupled with tandem mass spectrometry revealed that FAl-containing meibum lipids (wax monoesters and types 1ω, 2α, and 2ω wax diesters) with a hydroxyl group at position 1 were almost completely absent in Far2 KO mice. The levels of di-unsaturated (O-acyl)-ω-hydroxy fatty acids were higher in Far2 KO mice than in wild type mice, but those of tri-unsaturated ones were comparable, suggesting the presence of two synthesis pathways for type 1ω wax diesters. These results indicate the importance of FAl-containing meibum lipids in the formation of a functional tear film lipid layer. In addition, our study provides clues to the molecular mechanism of the biosynthesis of meibum lipids.
巻・号 36(4)
ページ e22216
公開日 2022-4-1
DOI 10.1096/fj.202101733R
PMID 35238077
MeSH Acyl-CoA Dehydrogenase / metabolism Aldehyde Oxidoreductases / metabolism Animals Dry Eye Syndromes* / metabolism Fatty Alcohols / analysis Fatty Alcohols / metabolism Meibomian Glands / metabolism Mice Mice, Knockout Tears* / metabolism
IF 4.966
リソース情報
ヒト・動物細胞 293T(RCB2202)