Department of Medicine, New York University School of Medicine, New York, New York, USA.
Curr Opin Lipidol. 2011 Apr;22(2):86-92. doi: 10.1097/MOL.0b013e3283428d9d.
Although the role for microRNAs (miRNAs) in regulating multiple physiological processes including apoptosis, cell differentiation, and cancer is well established, the importance of these tiny RNAs in regulating lipid metabolism has only recently been uncovered. This review summarizes the evidence for a critical role of miRNAs in regulating lipid metabolism.
Lipid metabolism is tightly regulated at the cellular level. In addition to classic transcriptional regulation of cholesterol metabolism (e.g. by SREBP and LXR), members of a class of noncoding RNAs termed miRNAs have now been identified to be potent post-transcriptional regulators of lipid metabolism genes involved in cholesterol homeostasis and fatty acid oxidation. Several reports have recently shown that miR-33 regulates cholesterol efflux and HDL biogenesis by downregulating the expression of the ABC transporters, ABCA1 and ABCG1. In addition, miR-33 also inhibits the translation of several transcripts encoding proteins involved in fatty acid β-oxidation including CPT1a, CROT, and HADHB, thereby reducing fatty acid degradation. Other miRNAs including miR-122, miR-370, miR-335, and miR-378/378*, miR-27 and miR-125a-5p have been implicated in regulating cholesterol homeostasis, fatty acid metabolism and lipogenesis.
Recent advances in the understanding of the regulation of lipid metabolism indicate that miRNAs play major roles in regulating cholesterol and fatty acid metabolism. These new findings may open new avenues for the treatment of dyslipidemias.
尽管 microRNAs（miRNAs）在调节包括细胞凋亡、细胞分化和癌症在内的多种生理过程中的作用已得到充分证实，但这些微小 RNA 在调节脂质代谢中的重要性最近才被发现。本综述总结了 miRNA 在调节脂质代谢中的关键作用的证据。
细胞水平的脂质代谢受到严格调控。除了胆固醇代谢的经典转录调控（例如 SREBP 和 LXR）外，现在已经确定一类称为 miRNA 的非编码 RNA 成员是参与胆固醇稳态和脂肪酸氧化的脂质代谢基因的强有力的转录后调控因子。最近有几项报道表明，miR-33 通过下调 ABC 转运蛋白 ABCA1 和 ABCG1 的表达来调节胆固醇外排和 HDL 生成。此外，miR-33 还抑制编码参与脂肪酸 β-氧化的几种蛋白的转录物的翻译，包括 CPT1a、CROT 和 HADHB，从而减少脂肪酸降解。其他 miRNA，包括 miR-122、miR-370、miR-335 和 miR-378/378*、miR-27 和 miR-125a-5p，也被认为参与调节胆固醇稳态、脂肪酸代谢和脂肪生成。
对脂质代谢调控的理解的最新进展表明，miRNAs 在调节胆固醇和脂肪酸代谢中起着重要作用。这些新发现可能为治疗血脂异常开辟新途径。
