Targeted disruption of stearoyl-CoA desaturase1 gene in mice causes atrophy of sebaceous and meibomian glands and depletion of wax esters in the eyelid
Targeted disruption of stearoyl-CoA desaturase1 gene in mice causes atrophy of sebaceous and meibomian glands and depletion of wax esters in the eyelid
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DOI：
10.1093/jn/131.9.2260
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发表时间：
2001-09-01
影响因子：
4.2
通讯作者：
Ntambi, JM
中科院分区：
文献类型：
--
作者：
Miyazaki, M;Man, WC;Ntambi, JM
硬脂酰辅酶a去饱和酶（SCD）是细胞合成单不饱和脂肪酸（MUFA）的微粒体限速酶，主要是油酸酯（18:1）和棕榈油酸酯（16:1），它们是膜磷脂、胆固醇酯和甘油三酯的主要MUFA。小鼠中存在三种特征明确的SCD亚型，SCD1、SCD2和SCD3。为了研究SCD1的生理功能，我们制造了SCD1 null （SCD1 -/-）小鼠。SCD1 -/-小鼠皮肤和眼睑缺乏甘油三酯和胆固醇酯，眼睑也缺乏蜡酯。此外，SCD1 -/-小鼠的眼睑和皮肤具有更高水平的游离胆固醇。SCD1 -/-小鼠出现皮肤异常和窄眼裂，皮脂腺和睑板腺萎缩。食用含有高水平油酸的饮食，不能使SCD1 -/-小鼠的甘油三酯、胆固醇酯和蜡酯的水平恢复到野生型小鼠眼睑的水平。这些结果揭示了SCD在胆固醇稳态以及正常皮肤和眼睑功能所需的胆固醇酯、甘油三酯和蜡酯的新生生物合成中的生理作用。
Stearoyl-CoA desaturase (SCD) is a microsomal rate-limiting enzyme in the cellular synthesis of monounsaturated fatty acids (MUFA), mainly oleate (18:1) and palmitoleate (16:1), which are the major MUFA of membrane phospholipids, cholesterol esters and triglycerides. Three well-characterized isoforms of SCD, SCD1, SCD2 and SCD3, exist in mice. To investigate the physiologic functions of SCD1, we generated SCD1 null (SCD1 -/-) mice. The skin and eyelid of SCD1 -/- mice are deficient in triglycerides and cholesterol esters, and the eyelid also is deficient in wax esters. Furthermore, the eyelid and skin of SCD1 -/- mice have higher levels of free cholesterol. SCD1 -/- mice develop cutaneous abnormalities and narrow eye fissure with atrophic sebaceous and meibomian glands. Consumption of diets containing high levels of oleate, failed to restore the levels of triglycerides, cholesterol esters and wax esters in SCD1 -/- mice to the levels found in the eyelid of wild-type mice. These results reveal a physiologic role of SCD in cholesterol homeostasis as well as in the de novo biosynthesis of cholesterol esters, triglycerides and wax esters required for normal skin and eyelid function.