Vienberg S, Geiger J, Madsen S, Dalgaard L T
Center for Basic Metabolic Research, Faculty of Health, University of Copenhagen, Copenhagen, Denmark.
Department of Science and Environment, Roskilde University, Roskilde, Denmark.
Acta Physiol (Oxf). 2017 Feb;219(2):346-361. doi: 10.1111/apha.12681. Epub 2016 Apr 5.
MicroRNAs (miRNAs) have within the past decade emerged as key regulators of metabolic homoeostasis. Major tissues in intermediary metabolism important during development of the metabolic syndrome, such as β-cells, liver, skeletal and heart muscle as well as adipose tissue, have all been shown to be affected by miRNAs. In the pancreatic β-cell, a number of miRNAs are important in maintaining the balance between differentiation and proliferation (miR-200 and miR-29 families) and insulin exocytosis in the differentiated state is controlled by miR-7, miR-375 and miR-335. MiR-33a and MiR-33b play crucial roles in cholesterol and lipid metabolism, whereas miR-103 and miR-107 regulates hepatic insulin sensitivity. In muscle tissue, a defined number of miRNAs (miR-1, miR-133, miR-206) control myofibre type switch and induce myogenic differentiation programmes. Similarly, in adipose tissue, a defined number of miRNAs control white to brown adipocyte conversion or differentiation (miR-365, miR-133, miR-455). The discovery of circulating miRNAs in exosomes emphasizes their importance as both endocrine signalling molecules and potentially disease markers. Their dysregulation in metabolic diseases, such as obesity, type 2 diabetes and atherosclerosis stresses their potential as therapeutic targets. This review emphasizes current ideas and controversies within miRNA research in metabolism.
在过去十年中,微小RNA(miRNA)已成为代谢稳态的关键调节因子。在代谢综合征发展过程中起重要作用的中间代谢主要组织,如β细胞、肝脏、骨骼肌和心肌以及脂肪组织,均已被证明会受到miRNA的影响。在胰腺β细胞中,许多miRNA在维持分化与增殖之间的平衡方面很重要(miR - 200和miR - 29家族),而分化状态下的胰岛素胞吐作用则由miR - 7、miR - 375和miR - 335控制。miR - 33a和miR - 33b在胆固醇和脂质代谢中起关键作用,而miR - 103和miR - 107调节肝脏胰岛素敏感性。在肌肉组织中,一定数量的miRNA(miR - 1、miR - 133、miR - 206)控制肌纤维类型转换并诱导肌源性分化程序。同样,在脂肪组织中,一定数量的miRNA控制白色脂肪细胞向棕色脂肪细胞的转化或分化(miR - 365、miR - 133、miR - 455)。外泌体中循环miRNA的发现强调了它们作为内分泌信号分子和潜在疾病标志物的重要性。它们在肥胖、2型糖尿病和动脉粥样硬化等代谢疾病中的失调突出了它们作为治疗靶点的潜力。本综述强调了miRNA代谢研究中的当前观点和争议。