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维生素D和ω-3脂肪酸通过协调CHROME/APOA1-AS/ABCA1/APOA1环境在改善多发性硬化症患者高密度脂蛋白生物合成中的作用。

Role of vitamin D and omega 3 fatty acids in improving HDL biogenesis among multiple sclerosis patients via orchestrating CHROME/APOA1-AS/ABCA1/APOA1 milieu.

作者信息

Abd-Elmawla Mai A, Ghaiad Heba R, Nooh Mohammed M, Amer Mai A, El-Ghoneimy Lobna Talaat, Mehana Noha A

机构信息

Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

出版信息

J Nutr Biochem. 2025 Nov;145:110007. doi: 10.1016/j.jnutbio.2025.110007. Epub 2025 Jun 16.

DOI:10.1016/j.jnutbio.2025.110007
PMID:40532959
Abstract

Clinical approaches that could correct the disturbed lipid profile may improve neurological disturbances in multiple sclerosis (MS) patients. However, the underlying mechanisms are still not well understood. The study aimed to characterize the performance of vitamin D (Vit.D) and omega 3 fatty acid (ω3) in adjusting the lipid profile of MS patients via modulating CHROME/APOA1-AS/ABCA1/APOA1 along with sphingosine kinase (SPHK)-1/2, and sphingosine 1-phosphate receptors (S1PR)-1/5. 72 MS patients were recruited for this study; 25 received Vit.D, 21 received ω3, and 26 didn't receive any supplementation. Blood samples were collected and then plasma were separated for further biochemical and molecular investigations. Both vit.D or ω3 improved the lipid profile in the studied groups as well as elevated the expression of the lncRNA CHROME, the concentrations of ABCA1 and ApoA1 along with lowering APOA1-AS relative to MS patients without supplementation. Vit.D supplementation group revealed higher levels of SPHK1 and lower levels of SPHK2, whereas ω3 supplementation reduced both S1PR1 and S1PR5 relative to the MS control group. This study demonstrated the beneficial role of Vit.D and ω3 supplementation in adjusting the lipid profile of MS patients via modulating ABCA1 and ApoA1 and their upstream regulators CHROME and APOA1-AS. The administration of Vit.D upregulated SPHK1 and downregulated SPHK2 gene expression. On the other hand, ω3 supplements downregulated S1PR1 and S1PR5 gene expression in MS patients.

摘要

能够纠正紊乱血脂谱的临床方法可能会改善多发性硬化症(MS)患者的神经功能障碍。然而,其潜在机制仍未完全明确。本研究旨在通过调节CHROME/APOA1-AS/ABCA1/APOA1以及鞘氨醇激酶(SPHK)-1/2和鞘氨醇-1-磷酸受体(S1PR)-1/5来表征维生素D(Vit.D)和ω-3脂肪酸(ω3)在调节MS患者血脂谱方面的作用。本研究招募了72例MS患者;25例接受Vit.D治疗,21例接受ω3治疗,26例未接受任何补充剂。采集血样,然后分离血浆进行进一步的生化和分子研究。与未补充的MS患者相比,Vit.D或ω3均改善了研究组的血脂谱,同时提高了lncRNA CHROME的表达、ABCA1和载脂蛋白A1(ApoA1)的浓度,并降低了APOA1-AS的水平。与MS对照组相比,Vit.D补充组显示出较高水平的SPHK1和较低水平的SPHK2,而ω3补充组降低了S1PR1和S1PR5的水平。本研究证明了Vit.D和ω3补充剂通过调节ABCA1和ApoA1及其上游调节因子CHROME和APOA1-AS在调节MS患者血脂谱方面的有益作用。Vit.D的给药上调了SPHK1并下调了SPHK2基因表达。另一方面,ω3补充剂下调了MS患者的S1PR1和S1PR5基因表达。

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