载脂蛋白 D 在抗炎方向调节脂质介质和骨桥蛋白,Inflammation Research

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载脂蛋白 D 在抗炎方向调节脂质介质和骨桥蛋白
Inflammation Research ( IF 4.8 ) Pub Date : 2022-12-19 , DOI: 10.1007/s00011-022-01679-8
Makoto Kurano _{1,

2,

3} , Kazuhisa Tsukamoto _{4,

5} , Shigeo Kamitsuji ₆ , Naoyuki Kamatani ₆ , Koji Hasegawa ₅ , Masumi Hara ₇ , Toshio Ishikawa ₄ , Yutaka Yatomi ₁ , Tamio Teramoto _{2,

3}

Affiliation

背景

已提出 HDL 具有抗炎特性；然而，详细机制尚未完全阐明。

方法

我们研究了载脂蛋白 D (ApoD) 在饮食诱导的肥胖小鼠模型和脂多糖诱导的脓毒症小鼠模型的炎症发病机制中的作用以及体外实验。此外，我们分析了人类受试者的血清 ApoD 水平。

结果

人 ApoD 的过表达降低了两种小鼠模型中的血浆 IL-6 和 TNF-α 水平。脂质组学分析表明，ApoD 与花生四烯酸、二十碳五烯酸和二十二碳六烯酸及其代谢物、抗炎分子鞘氨醇 1-磷酸的增加以及促炎性溶血磷脂酸和溶血磷脂酰肌醇的减少有关。含有 ApoD 的脂蛋白可能直接结合二十碳五烯酸和二十二碳六烯酸。溶血磷脂酸和鞘氨醇 1-磷酸水平的调节分别由自分泌运动因子表达的抑制和载脂蛋白 M (ApoM) 的升高引起。此外，ApoD 负向调节骨桥蛋白，一种促炎性脂肪因子。ApoD 对 PPARg 的激活可能会抑制自分泌运动因子和骨桥蛋白。

结论

ApoD 是一种抗炎载脂蛋白，可在抗炎方向调节脂质介质和骨桥蛋白。

"点击查看英文标题和摘要"

Apolipoprotein D modulates lipid mediators and osteopontin in an anti-inflammatory direction

Background

HDL has been proposed to possess anti-inflammatory properties; however, the detail mechanisms have not been fully elucidated.

Methods

We investigated the roles of Apolipoprotein D (ApoD) in the pathogenesis of inflammation in the mouse model of diet-induced obesity and that of lipopolysaccharide-induced sepsis and the in vitro experiments. Furthermore, we analyzed serum ApoD levels in human subjects.

Results

The overexpression of human ApoD decreased the plasma IL-6 and TNF-a levels in both mice models. Lipidomics analyses demonstrated association of ApoD with increase of arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, as well as of their metabolites, and of the anti-inflammatory molecule sphingosine 1-phosphate, and decrease of proinflammatory lysophosphatidic acids and lysophosphatidylinositol. ApoD-containing lipoproteins might directly bind eicosapentaenoic acid and docosahexaenoic acid. The modulations of the lysophosphatidic acid and sphingosine 1-phosphate levels resulted from the suppression of autotaxin expression and elevation of apolipoprotein M (ApoM), respectively. Moreover, ApoD negatively regulated osteopontin, a proinflammatory adipokine. The activation of PPARg by ApoD might suppress autotaxin and osteopontin. Serum ApoD levels were negatively correlated with the serum osteopontin and autotaxin levels and, positively with serum ApoM levels.