Apolipoprotein A‐I in mouse cerebrospinal fluid derives from the liver and intestine via plasma high‐density lipoproteins assembled by ABCA1 and LCAT,FEBS Letters

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Apolipoprotein A‐I in mouse cerebrospinal fluid derives from the liver and intestine via plasma high‐density lipoproteins assembled by ABCA1 and LCAT
FEBS Letters ( IF 3.0 ) Pub Date : 2020-10-20 , DOI: 10.1002/1873-3468.13950
Maki Tsujita ₁ , Boris Vaisman ₂ , Liu Chengyu ₃ , Kasey C Vickers ₄ , Kei-Ichiro Okuhira ₅ , Sten Braesch-Andersen ₆ , Alan T Remaley ₂

Affiliation

Apolipoprotein (apo) A-I, the major structural protein of high-density lipoprotein (HDL), is present in human and mouse cerebrospinal fluid (CSF) despite its lack of expression in brain cells. To identify the origin of apoA-I in CSF, we generated intestine-specific and liver-specific Apoa1 knockout mice (Apoa1ΔInt and Apoa1Δliv mice, respectively). Lipoprotein profiles of Apoa1ΔInt and Apoa1ΔLiv mice resembled those of control littermates, whereas knockout of Apoa1 in both intestine and liver (Apoa1ΔIntΔLiv ) resulted in a 60-percent decrease in HDL-cholesterol levels, thus strongly mimicking the Apoa1-/- mice. Immunoassays revealed that mouse apoA-I was not present in the CSF of the Apoa1ΔIntΔLiv mice. Furthermore, apoA-I levels in CSF were highly correlated with plasma spherical HDL levels, which were regulated by ABCA1 and LCAT. Collectively, these results suggest that apoA-I protein in CSF originates in liver and small intestine and is taken up from the plasma.

中文翻译：

小鼠脑脊液中的载脂蛋白 A-I 通过由 ABCA1 和 LCAT 组装的血浆高密度脂蛋白来源于肝脏和肠道

载脂蛋白 (apo) AI 是高密度脂蛋白 (HDL) 的主要结构蛋白，尽管在脑细胞中缺乏表达，但仍存在于人和小鼠脑脊液 (CSF) 中。为了确定 CSF 中 apoA-I 的起源，我们生成了肠道特异性和肝脏特异性 Apoa1 敲除小鼠（分别为 Apoa1ΔInt 和 Apoa1Δliv 小鼠）。Apoa1ΔInt 和 Apoa1ΔLiv 小鼠的脂蛋白谱与对照同窝小鼠相似，而在肠道和肝脏中敲除 Apoa1 (Apoa1ΔIntΔLiv) 导致 HDL-胆固醇水平降低 60%，从而强烈模仿 Apoa1-/- 小鼠。免疫测定显示，ApoA1ΔIntΔLiv 小鼠的脑脊液中不存在小鼠 apoA-I。此外，脑脊液中的 apoA-I 水平与血浆球形 HDL 水平高度相关，后者受 ABCA1 和 LCAT 的调节。集体，

更新日期：2020-10-20

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