Busnelli Marco, Manzini Stefano, Colombo Alice, Franchi Elsa, Chiara Matteo, Zaffaroni Gaia, Horner David, Chiesa Giulia
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy.
Department of Biosciences, Università degli Studi di Milano, Milano, Italy.
iScience. 2023 Aug 11;26(9):107615. doi: 10.1016/j.isci.2023.107615. eCollection 2023 Sep 15.
The molecular mechanism by which lipid/lipoprotein biosynthesis is regulated in mammals involves a very large number of genes that are subject to multiple levels of regulation. miRNAs are recognized contributors to lipid homeostasis at the post-transcriptional level, although the elucidation of their role is made difficult by the multiplicity of their targets and the ability of more miRNAs to affect the same mRNAs. In this study, an evaluation of how miRNA expression varies in organs playing a key role in lipid/lipoprotein metabolism was conducted in control mice and in two mouse models carrying genetic ablations which differently affect low-density lipoprotein metabolism. Mice were fed a lipid-poor standard diet and a diet enriched in cholesterol and saturated fat. The results obtained showed that there are no miRNAs whose expression constantly vary with dietary or genetic changes. Furthermore, it appears that diet, more than genotype, impacts on organ-specific miRNA expression profiles.
哺乳动物中脂质/脂蛋白生物合成的调控分子机制涉及大量受多种调控水平影响的基因。微小RNA(miRNA)被认为是转录后水平脂质稳态的贡献者,尽管由于其靶标的多样性以及多个miRNA影响相同mRNA的能力,使得阐明它们的作用变得困难。在本研究中,我们对对照小鼠以及两种携带不同程度影响低密度脂蛋白代谢的基因缺失的小鼠模型,评估了在脂质/脂蛋白代谢中起关键作用的器官中miRNA表达如何变化。给小鼠喂食低脂质标准饮食以及富含胆固醇和饱和脂肪的饮食。获得的结果表明,没有miRNA的表达会随着饮食或基因变化而持续改变。此外,似乎饮食比基因型对器官特异性miRNA表达谱的影响更大。