Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, E-50013 Zaragoza, Spain.
Departamento de Farmacología, Fisiología, Medicina Legal y Forense, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, E-50013 Zaragoza, Spain.
Int J Mol Sci. 2022 Apr 10;23(8):4172. doi: 10.3390/ijms23084172.
Squalene is a natural bioactive triterpene and an important intermediate in the biosynthesis of sterols. To assess the effect of this compound on the hepatic transcriptome, RNA-sequencing was carried out in two groups of male New Zealand rabbits fed either a diet enriched with 1% sunflower oil or the same diet with 0.5% squalene for 4 weeks. Hepatic lipids, lipid droplet area, squalene, and sterols were also monitored. The Squalene administration downregulated 9 transcripts and upregulated 13 transcripts. The gene ontology of transcripts fitted into the following main categories: transporter of proteins and sterols, lipid metabolism, lipogenesis, anti-inflammatory and anti-cancer properties. When the results were confirmed by RT-qPCR, rabbits receiving squalene displayed significant hepatic expression changes of (), , , , , , , , , , and . A squalene-enriched diet increased hepatic levels of squalene, lanosterol, dihydrolanosterol, lathosterol, zymostenol and desmosterol. Strong correlations were found among specific sterols and some squalene-changed transcripts. Incubation of the murine AML12 hepatic cell line in the presence of lanosterol, dihydrolanosterol, zymostenol and desmosterol reproduced the observed changes in the expressions of , and . In conclusion, these findings indicate that the squalene and post-squalene metabolites play important roles in hepatic transcriptional changes required to protect the liver against malfunction.
角鲨烯是一种天然生物活性三萜烯，也是甾醇生物合成的重要中间产物。为了评估该化合物对肝脏转录组的影响，我们对两组雄性新西兰兔进行了研究，一组喂食富含 1%葵花籽油的饮食，另一组喂食相同饮食但添加 0.5%角鲨烯的饮食，为期 4 周。同时还监测了肝脏脂质、脂滴面积、角鲨烯和甾醇。角鲨烯处理下调了 9 个转录本，上调了 13 个转录本。转录本的基因本体论符合以下主要类别：蛋白质和甾醇的转运蛋白、脂质代谢、脂肪生成、抗炎和抗癌特性。当通过 RT-qPCR 确认结果时，接受角鲨烯的兔子显示出显著的肝脏表达变化的 ()， ()， ()， ()， ()， ()， ()， ()， ()和 ()。富含角鲨烯的饮食增加了肝脏中的角鲨烯、羊毛甾醇、二氢羊毛甾醇、麦角固醇、酵母固醇和去甲胆固醇水平。特定甾醇与一些角鲨烯变化转录本之间存在强烈相关性。在存在羊毛甾醇、二氢羊毛甾醇、酵母固醇和去甲胆固醇的情况下孵育鼠 AML12 肝细胞系，复制了观察到的 ()， ()和 ()表达变化。总之，这些发现表明角鲨烯和角鲨烯后代谢物在保护肝脏免受功能障碍的肝脏转录变化中发挥重要作用。
