Department of Molecular Physiology and Biophysics, Vanderbilt University.
Department of Medicine, Vanderbilt University Medical Center, Nashville, USA.
Curr Opin Lipidol. 2019 Jun;30(3):165-171. doi: 10.1097/MOL.0000000000000603.
The purpose of the review is to discuss recent advances in microRNA (miRNA) regulation of lipid metabolism and highlight the importance of miRNA-mediated gene regulation in dyslipidemia and fatty liver disease. This article reviews examples of miRNAs that bridge disparate metabolic pathways in the liver. For example, we highlight miRNAs that are regulated by the sterol-sensing pathway in the liver that in turn regulate cellular or systemic cholesterol, fatty acid, and glucose levels.
The most widely studied of these miRNAs are miR-33a/b; however, we recently reported that miRNAs in the miR-183/96/182 cluster are also likely regulated by hepatic cholesterol content and mediate the observed glucose-lowering effects of the bile acid sequestrant colesevelam through the sterol-sensing pathway. In addition, several other hepatic and adipose miRNAs have been recently demonstrated to be key regulators of cellular lipid synthesis, storage, and catabolism, as well as systemic lipid metabolism. Moreover, many of these miRNAs are altered in fatty liver disease and dyslipidemia.
miRNAs are not just fine-tuners of lipid metabolism, but critical regulatory factors in lipid homeostasis and health. Loss of these miRNA regulatory modules very likely contributes to the underlying metabolic defects observed in lipid disorders.
本文旨在讨论微小 RNA（miRNA）对脂质代谢的调控作用的最新进展，并强调 miRNA 介导的基因调控在血脂异常和脂肪肝疾病中的重要性。本文综述了 miRNA 连接肝脏中不同代谢途径的例子。例如，我们强调了受肝脏固醇感应途径调控的 miRNAs，这些 miRNAs 反过来又调节细胞或全身胆固醇、脂肪酸和葡萄糖水平。
这些 miRNA 中研究最广泛的是 miR-33a/b；然而，我们最近报道，miR-183/96/182 簇中的 miRNAs 也可能受肝胆固醇含量的调控，并通过固醇感应途径介导胆汁酸螯合剂考来烯胺的观察到的降血糖作用。此外，最近还发现其他几种肝和脂肪组织 miRNAs 是细胞脂质合成、储存和分解代谢以及全身脂质代谢的关键调节因子。此外，这些 miRNA 中的许多在脂肪肝疾病和血脂异常中发生改变。
miRNA 不仅是脂质代谢的微调因子，还是脂质动态平衡和健康的关键调节因子。这些 miRNA 调节模块的缺失很可能导致脂质紊乱中观察到的潜在代谢缺陷。
