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脂肪酸调节 Caco-2 单层细胞中胆固醇吸收关键蛋白的表达水平。

Fatty acids modulate the expression levels of key proteins for cholesterol absorption in Caco-2 monolayer.

机构信息

National Research and Development Center for Egg Processing, College of Food Science and Technology, Huazhong Agricultural University, 430070, Wuhan, Hubei, People's Republic of China.

School of Laboratory Medicine, Hubei University of Chinese Medicine, 1 Huangjia Lake West Road, Wuhan, 430065, China.

出版信息

Lipids Health Dis. 2018 Feb 20;17(1):32. doi: 10.1186/s12944-018-0675-y.

DOI:10.1186/s12944-018-0675-y
PMID:29463265
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5819267/
Abstract

BACKGROUND

Fatty acids have been shown to modulate intestinal cholesterol absorption in cells and animals, a process that is mediated by several transporter proteins. Of these proteins, Niemann-Pick C1-Like 1 (NPC1L1) is a major contributor to this process. The current study investigates the unknown mechanism by which fatty acids modulate cholesterol absorption.

METHODS

We evaluated the effects of six fatty acids palmitic acid (PAM), oleic acid (OLA), linoleic acid (LNA), arachidonic acid (ARA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cholesterol uptake and transport in human enterocytes Caco-2 cells, and on the mRNA expression levels of NPC1L1, others proteins (ABCG5, ABCG8, ABCA1, ACAT2, MTP, Caveolin 1, Annexin-2) involved in cholesterol absorption, and SREBP-1 and SREBP-2 that are responsible for lipid metabolism.

RESULTS

The polyunsaturated fatty acids (PUFAs), especially for EPA and DHA, dose-dependently inhibited cholesterol uptake and transport in Caco-2 monolayer, while saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) had no inhibitory effects. EPA and DHA inhibited cholesterol absorption in Caco-2 monolayer might be caused by down-regulating NPC1L1 mRNA and protein levels, which were associated with inhibition of SREBP-1/- 2 mRNA expression levels.

CONCLUSION

Results from this study indicate that functional food containing high PUFAs may have potential therapeutic benefit to reduce cholesterol absorption. Further studies on this topic may provide approaches to control lipid metabolism and to promote health.

摘要

背景

脂肪酸已被证明可调节细胞和动物肠道胆固醇吸收,这一过程由几种转运蛋白介导。在这些蛋白中,NPC1L1 是该过程的主要贡献者。本研究旨在探讨脂肪酸调节胆固醇吸收的未知机制。

方法

我们评估了六种脂肪酸(棕榈酸(PAM)、油酸(OLA)、亚油酸(LNA)、花生四烯酸(ARA)、二十碳五烯酸(EPA)和二十二碳六烯酸(DHA))对人肠细胞 Caco-2 摄取和转运胆固醇的影响,以及 NPC1L1 及其它参与胆固醇吸收的蛋白(ABCG5、ABCG8、ABCA1、ACAT2、MTP、Caveolin 1、Annexin-2)和负责脂质代谢的 SREBP-1 和 SREBP-2 的 mRNA 表达水平。

结果

多不饱和脂肪酸(PUFAs),特别是 EPA 和 DHA,呈剂量依赖性地抑制 Caco-2 单层中的胆固醇摄取和转运,而饱和脂肪酸(SFAs)和单不饱和脂肪酸(MUFAs)则无抑制作用。EPA 和 DHA 抑制 Caco-2 单层中的胆固醇吸收可能是通过下调 NPC1L1 mRNA 和蛋白水平引起的,这与 SREBP-1/-2 mRNA 表达水平的抑制有关。

结论

本研究结果表明,富含多不饱和脂肪酸的功能性食品可能具有降低胆固醇吸收的潜在治疗益处。进一步研究该课题可能为控制脂质代谢和促进健康提供方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/5819267/22fa1fddbb7f/12944_2018_675_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/5819267/bfbdf4039ac6/12944_2018_675_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/5819267/26ebb21fb980/12944_2018_675_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/5819267/86e48b4f488b/12944_2018_675_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/5819267/22fa1fddbb7f/12944_2018_675_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/5819267/bfbdf4039ac6/12944_2018_675_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/5819267/26ebb21fb980/12944_2018_675_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/5819267/86e48b4f488b/12944_2018_675_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cc/5819267/22fa1fddbb7f/12944_2018_675_Fig4_HTML.jpg

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