From the Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, Oregon 97239 and.
J Biol Chem. 2014 Jan 31;289(5):2482-8. doi: 10.1074/jbc.R113.516716. Epub 2013 Dec 19.
The skin is the single largest organ in humans, serving as a major barrier to infection, water loss, and abrasion. The functional diversity of skin requires the synthesis of large amounts of lipids, such as triglycerides, wax esters, squalene, ceramides, free cholesterol, free fatty acids, and cholesterol and retinyl esters. Some of these lipids are used as cell membrane components, signaling molecules, and a source of energy. An important class of lipid metabolism enzymes expressed in skin is the Δ(9)-desaturases, which catalyze the synthesis in Δ(9)-monounsaturated lipids, primarily oleoyl-CoA (18:1n-9) and palmitoyl-CoA (16:1n-7), the major monounsaturated fatty acids in cutaneous lipids. Mice with a deletion of the Δ(9)-desaturase-1 isoform (SCD1) either globally (Scd1(-/-)) or specifically in the skin (skin-specific Scd1-knockout; SKO) present with marked changes in cutaneous lipids and skin integrity. Interestingly, these mice also exhibit increased whole body energy expenditure, protection against diet-induced adiposity, hepatic steatosis, and glucose intolerance. The increased energy expenditure in skin-specific Scd1-knockout (SKO) mice is a surprising phenotype, as it links cutaneous lipid homeostasis with whole body energy balance. This minireview summarizes the role of skin SCD1 in regulating skin integrity and whole body energy homeostasis and offers a discussion of potential pathways that may connect these seemingly disparate phenotypes.
皮肤是人体最大的单一器官,充当着抵御感染、水分流失和磨损的主要屏障。皮肤的功能多样性需要合成大量的脂质,如甘油三酯、蜡酯、角鲨烯、神经酰胺、游离胆固醇、游离脂肪酸以及胆固醇和视黄醇酯。其中一些脂质被用作细胞膜成分、信号分子和能量来源。在皮肤中表达的一类重要的脂质代谢酶是 Δ(9)-去饱和酶,它催化 Δ(9)-单不饱和脂质的合成,主要是油酰辅酶 A(18:1n-9)和棕榈酰辅酶 A(16:1n-7),这是皮肤脂质中的主要单不饱和脂肪酸。Δ(9)-去饱和酶-1 同工型(SCD1)全局缺失(Scd1(-/-))或特异性缺失(皮肤特异性 Scd1 敲除;SKO)的小鼠表现出皮肤脂质和皮肤完整性的明显变化。有趣的是,这些小鼠还表现出全身能量消耗增加、对饮食诱导的肥胖、肝脂肪变性和葡萄糖不耐受的保护作用。皮肤特异性 Scd1 敲除(SKO)小鼠的能量消耗增加是一个令人惊讶的表型,因为它将皮肤脂质稳态与全身能量平衡联系起来。这篇综述总结了皮肤 SCD1 在调节皮肤完整性和全身能量平衡中的作用,并讨论了可能连接这些看似不同表型的潜在途径。