Dataset Information

Alisol B 23-acetate activates ABCG5/G8 in the jejunum via the LXR?/ACAT2 pathway to relieve atherosclerosis in ovariectomized ApoE^-/- mice.

ABSTRACT: Phytosterols have been shown to improve blood lipid levels and treat atherosclerosis. This research investigated the effects of phytosterol Alisol B 23-acetate (AB23A) on jejunum lipid metabolism and atherosclerosis. The results show that intragastric administration of AB23A can significantly reduce atherosclerotic plaque area and lipid accumulation in the jejunum of ovariectomized ApoE^-/- mice fed a high-fat diet and can also improve the lipid mass spectra of the plasma and jejunum. In vitro studies have shown that AB23A can increase cholesterol outflow in Caco-2 cells exposed to high fat concentrations and increase the expression of ATP-binding cassette transfer proteins G5/G8 (ABCG5/G8), the liver X receptor ? (LXR?). Furthermore, inhibition of LXR? can significantly eliminate the active effect of AB23A on decreasing intracellular lipid accumulation. We also confirmed that AB23A has a negative effect on Acyl-CoA cholesterol acyltransferase 2 (ACAT2) in Caco-2 cells cultured in the high concentrations of fat, and we found that AB23A further reduces ACAT2 expression in cells treated with the ACAT2 inhibitor pyripyropene or transfected with ACAT2 siRNA. In conclusion, we confirmed that AB23A can reduce the absorption of dietary lipids in the jejunum by affecting the LXR?-ACAT2-ABCG5/G8 pathway and ultimately exert an anti-atherosclerotic effect.

SUBMITTER: Yu XC

PROVIDER: S-EPMC7803561 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Alisol B 23-acetate activates ABCG5/G8 in the jejunum via the LXRα/ACAT2 pathway to relieve atherosclerosis in ovariectomized ApoE<sup>-/-</sup> mice.

Yu Xi-Chao XC Fu Yu Y Bi Yun-Hui YH Zhang Wei-Wei WW Li Jun J Ji Tingting T Chao Ying Y Meng Qing-Hai QH Chen Qi Q Ma Meng-Hua MH Zhang Yu-Han YH Shan Jinjun J Bian Hui-Min HM

Aging 20201125 24

Phytosterols have been shown to improve blood lipid levels and treat atherosclerosis. This research investigated the effects of phytosterol Alisol B 23-acetate (AB23A) on jejunum lipid metabolism and atherosclerosis. The results show that intragastric administration of AB23A can significantly reduce atherosclerotic plaque area and lipid accumulation in the jejunum of ovariectomized ApoE<sup>-/-</sup> mice fed a high-fat diet and can also improve the lipid mass spectra of the plasma and jejunum. ...[more]

PMID: 33234731

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Project description:BackgroundThe long-term excessive intake of exogenous cholesterol can lead to abnormally elevated blood lipid levels and induce cardiovascular and cerebrovascular diseases. However, the influence and relevance of exogenous cholesterol on plasma cholesterol components were still unclear, and the influence on intestinal lipid metabolism targets needs to be further explored.MethodsIn vivo, the C57BL/6 + NF group and ApoE-/- + NF group mice were fed a normal specific pathogen-free (SPF) diet; the ApoE-/- + HF group mice were fed a high-cholesterol SPF diet. The plasma and jejunum tissue homogenate were obtained for non-targeted lipid metabolomics. The lipid droplets in tissues were observed by transmission electron microscope and oil red O staining. Jejunum tissue morphology was observed by HE staining. The kits were used to detect lipid content in plasma, tissues, intestinal contents, and cells. Western blot, RT-PCR, immunohistochemistry (IHC), and immunofluorescence (IF) were used to observe the key target of lipid metabolism. In vitro, the final concentration of cholesterol was 100 μmol/L in Caco-cells. Oil red O staining, western blot, RT-PCR and immunofluorescence (IF) were used to observe the changes of lipid metabolism. Finally, the influence of liver X receptor alpha (LXRα) on intestinal cholesterol metabolism was clarified by applying the LXRα inhibitor GSK2033 and siRNA targeting LXRα.ResultsThe aortic arch and intestinal villi of the two groups of ApoE-/- mice showed apparent lesions and lipid accumulation, and there were significant changes in a variety of lipids in the plasma and jejunum. Additionally, jejunum LXRα was markedly activated. High cholesterol can significantly activate LXRα in Caco-2 cells. After LXRα was inhibited, the protein level of ATP-binding cassette transporter A1/G5/G8 (ABCA1/G5/G8) decreased, and the quantity and volume of intracellular lipids soared.ConclusionIn a high-cholesterol environment, the intestine promotes the excretion of cholesterol from the cell through the LXRα-ABCA1/G5/G8 pathway, reduces the intestinal intake of a variety of exogenous cholesterol, and reduces the risk of AS.

Dataset Information

Alisol B 23-acetate activates ABCG5/G8 in the jejunum via the LXR?/ACAT2 pathway to relieve atherosclerosis in ovariectomized ApoE^-/- mice.

Publications

Alisol B 23-acetate activates ABCG5/G8 in the jejunum via the LXRα/ACAT2 pathway to relieve atherosclerosis in ovariectomized ApoE<sup>-/-</sup> mice.

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Dataset Information

Alisol B 23-acetate activates ABCG5/G8 in the jejunum via the LXR?/ACAT2 pathway to relieve atherosclerosis in ovariectomized ApoE-/- mice.

Publications

Alisol B 23-acetate activates ABCG5/G8 in the jejunum via the LXRα/ACAT2 pathway to relieve atherosclerosis in ovariectomized ApoE<sup>-/-</sup> mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Alisol B 23-acetate activates ABCG5/G8 in the jejunum via the LXR?/ACAT2 pathway to relieve atherosclerosis in ovariectomized ApoE^-/- mice.