Reelin deficiency leads to aberrant lipid composition in mouse brain.
Reelin deficiency leads to aberrant lipid composition in mouse brain.
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DOI：
10.1016/j.bbrc.2018.09.089
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发表时间：
2018-10
影响因子：
3.1
通讯作者：
Tomoharu Mizukami;K. Ikeda;Y. Shimanaka;Katsunari Korogi;Chunyu Zhou;H. Takase;H. Tsuiji;N. Kono
中科院分区：
文献类型：
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作者：
Tomoharu Mizukami;K. Ikeda;Y. Shimanaka;Katsunari Korogi;Chunyu Zhou;H. Takase;H. Tsuiji;N. Kono
Reelin是哺乳动物大脑发育和功能所必需的分泌蛋白。Reelin的受体，载脂蛋白E受体2和极低密度脂蛋白受体，属于低密度脂蛋白受体家族，但不知道Reelin是否参与脑脂质代谢。在本研究中，我们对野生型和Reelin缺陷小鼠（reeler）的大脑皮层进行了脂质组学分析，发现reeler小鼠表现出磷脂的几种成分变化。首先，含有一种饱和脂肪酸（FA）和一种二十二碳六烯酸（DHA）或花生四烯酸（ARA）的磷脂的比例降低。其次，含有一个单不饱和脂肪酸（MUFA）和一个DHA或ARA的磷脂比例增加。第三，含有5，8，11-二十碳三烯酸或米德酸（MA）的磷脂比例增加。最后，硬脂酰辅酶A去饱和酶-1（SCD-1）的表达增加。由于MA的增加被视为多不饱和脂肪酸（PUFA）缺乏的指标，并且SCD-1的表达被PUFA抑制，这些结果强烈地表明，Reelin的损失导致PUFA缺乏。因此，MUFA和MA的合成响应于这种缺陷，部分通过诱导SCD-1的表达。本研究首次报道了Reelin在小鼠脑内FA组成的变化，为进一步研究Reelin在脑发育和功能中的新作用提供了基础。
Reelin is a secreted protein essential for the development and function of the mammalian brain. The receptors for Reelin, apolipoprotein E receptor 2 and very low-density lipoprotein receptor, belong to the low-density lipoprotein receptor family, but it is not known whether Reelin is involved in the brain lipid metabolism. In the present study, we performed lipidomic analysis of the cerebral cortex of wild-type and Reelin-deficient (reeler) mice, and found thatreelermice exhibited several compositional changes in phospholipids. First, the ratio of phospholipids containing one saturated fatty acid (FA) and one docosahexaenoic acid (DHA) or arachidonic acid (ARA) decreased. Secondly, the ratio of phospholipids containing one monounsaturated FA (MUFA) and one DHA or ARA increased. Thirdly, the ratio of phospholipids containing 5,8,11-eicosatrienoic acid, or Mead acid (MA), increased. Finally, the expression of stearoyl-CoA desaturase-1 (SCD-1) increased. As the increase of MA is seen as an index of polyunsaturated FA (PUFA) deficiency, and the expression of SCD-1 is suppressed by PUFA, these results strongly suggest that the loss of Reelin leads to PUFA deficiency. Hence, MUFA and MA are synthesized in response to this deficiency, in part by inducing SCD-1 expression. This is the first report of changes of FA composition in thereelermouse brain and provides a basis for further investigating the new role of Reelin in the development and function of the brain.