Depletion of Cholesteryl Esters Causes Meibomian Gland Dysfunction-Like Symptoms in a Soat1-Null Mouse Model
| Autor: | Igor A. Butovich, Amber Wilkerson, Seher Yuksel |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
cholesteryl esters Mutant Soat1/SOAT1 Meibomian gland Omega oxidation Catalysis meibogenesis Inorganic Chemistry lcsh:Chemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Biosynthesis Lipidomics medicine Physical and Theoretical Chemistry Molecular Biology lcsh:QH301-705.5 Spectroscopy mass spectrometry SOAT1 Organic Chemistry General Medicine Meibomian gland dysfunction Molecular biology Pathophysiology Computer Science Applications 030104 developmental biology medicine.anatomical_structure chemistry lcsh:Biology (General) lcsh:QD1-999 030221 ophthalmology & optometry Fatty acid elongation chromatography lipidomics sense organs |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 1583, p 1583 (2021) International Journal of Molecular Sciences Volume 22 Issue 4 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Previous studies on ablation of several key genes of meibogenesis related to fatty acid elongation, omega oxidation, and esterification into wax esters have demonstrated that inactivation of any of them led to predicted changes in the meibum lipid profiles and caused severe abnormalities in the ocular surface and Meibomian gland (MG) physiology and morphology. In this study, we evaluated the effects of Soat1 ablation that were expected to cause depletion of the second largest class of Meibomian lipids (ML)—cholesteryl esters (CE)—in a mouse model. ML of the Soat1-null mice were examined using liquid chromatography high-resolution mass spectrometry and compared with those of Soat1+/− and wild-type mice. Complete suppression of CE biosynthesis and simultaneous accumulation of free cholesterol (Chl) were observed in Soat1-null mice, while Soat1+/− mutants had normal Chl and CE profiles. The total arrest of the CE biosynthesis in response to Soat1 ablation transformed Chl into the dominant lipid in meibum accounting for at least 30% of all ML. The Soat1-null mice had clear manifestations of dry eye and MG dysfunction. Enrichment of meibum with Chl and depletion of CE caused plugging of MG orifices, increased meibum rigidity and melting temperature, and led to a massive accumulation of lipid deposits around the eyes of Soat1-null mice. These findings illustrate the role of Soat1/SOAT1 in the lipid homeostasis and pathophysiology of MG. |
| Databáze: | OpenAIRE |
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