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富含甘油三酯的餐后脂蛋白以脂肪酸依赖的方式促进人循环和鼠骨髓中性粒细胞中的脂质积累和载脂蛋白 B-48 受体转录活性。

Postprandial triglyceride-rich lipoproteins promote lipid accumulation and apolipoprotein B-48 receptor transcriptional activity in human circulating and murine bone marrow neutrophils in a fatty acid-dependent manner.

机构信息

Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, Consejo Superior de Investigaciones Científicas (CSIC), Seville, Spain.

Department of Cell Biology, University of Seville, Sevilla, Spain (B.B).

出版信息

Mol Nutr Food Res. 2017 Sep;61(9). doi: 10.1002/mnfr.201600879. Epub 2017 Apr 28.

DOI:10.1002/mnfr.201600879
PMID:28322000
Abstract

SCOPE

Postprandial triglyceride-rich lipoproteins (TRLs) promote atherosclerosis. Recent research points the bone marrow (BM) as a primary site in atherosclerosis. We elucidated how the acute administration of monounsaturated fatty acids (MUFAs) MUFAs, omega-3 polyunsaturated fatty acids (PUFAs) PUFAs and saturated fatty acids (SFAs) affects human circulating and murine BM neutrophil lipid accumulation and functionality.

METHODS AND RESULTS

Postprandial hypertriglyceridemia was induced in healthy subjects and Apoe mice by the acute administration of dietary fats enriched in MUFAs, PUFAs, or SFAs. Postprandial hypertriglyceridemia increased apolipoprotein-B48 receptor (ApoB48R) transcriptional activity that was linearly correlated with intracellular triglycerides (TGs) TGs accumulation in human circulating and murine BM neutrophils. MUFA and omega-3 PUFAs attenuated ApoB48R gene expression and intracellular TG accumulation compared to SFAs. TRLs induced apoB48R-dependent TG accumulation in human neutrophils ex vivo. Murine BM neutrophils showed a decrease in surface L-selectin and an increase in TNF-α and IL-1β mRNA expressions only after SFAs administration. TRLs enriched in SFAs induced BM neutrophil degranulation ex vivo suggesting cell priming/activation.

CONCLUSION

Postprandial TRLs disrupts the normal biology and function of circulating and BM neutrophils. MUFA- and omega-3 PUFA-rich dietary fats such as virgin olive oil or fish oil has the potential to prevent excessive neutrophil lipid accumulation and activation by targeting the fatty acid composition of TRLs.

摘要

研究范围

富含甘油三酯的餐后脂蛋白(TRLs)可促进动脉粥样硬化。最近的研究指出骨髓(BM)是动脉粥样硬化的主要部位。我们阐明了单不饱和脂肪酸(MUFAs)、ω-3 多不饱和脂肪酸(PUFAs)和饱和脂肪酸(SFAs)的急性给药如何影响人类循环和鼠 BM 中性粒细胞的脂质积累和功能。

方法和结果

通过急性给予富含 MUFAs、PUFAs 或 SFAs 的饮食脂肪,在健康受试者和 Apoe 小鼠中诱导餐后高甘油三酯血症。餐后高甘油三酯血症增加了载脂蛋白-B48 受体(ApoB48R)的转录活性,与人类循环和鼠 BM 中性粒细胞内的甘油三酯(TGs)积累呈线性相关。与 SFAs 相比,MUFA 和 ω-3 PUFAs 可减弱 ApoB48R 基因表达和细胞内 TG 积累。TRLs 可诱导人中性粒细胞体外依赖 apoB48R 的 TG 积累。只有在给予 SFAs 后,鼠 BM 中性粒细胞才会减少表面 L-选择素并增加 TNF-α 和 IL-1β mRNA 表达。富含 SFAs 的 TRLs 可诱导 BM 中性粒细胞体外脱颗粒,表明细胞启动/激活。

结论

餐后 TRLs 破坏了循环和 BM 中性粒细胞的正常生物学和功能。富含 MUFA 和 ω-3 PUFA 的饮食脂肪,如初榨橄榄油或鱼油,通过靶向 TRLs 的脂肪酸组成,有可能预防中性粒细胞脂质过度积累和激活。

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