Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan 250012, China.
Int J Mol Sci. 2021 Jan 7;22(2):550. doi: 10.3390/ijms22020550.
Alterations in miRNAs are associated with many metabolic disorders, such as type 2 diabetes (T2DM). The miR-23b/27b/24-1 cluster contains miR-23b, miR-27b, and miR-24-1, which are located within 881 bp on chromosome 9. Studies examining the roles of miR-23b, miR-27b, and miR-24-1 have demonstrated their multifaceted functions in variable metabolic disorders. However, their joint roles in metabolism in vivo remain elusive. To investigate this subject, we constructed miR-23b/27b/24-1 cluster knockout (KO) mice. Compared with wild-type (WT) mice, the KO mice exhibited impaired glucose tolerance, which was accompanied by a reduction in the respiratory exchange rate (RER). These alterations were more noticeable after a high-fat diet (HFD) induction. Hepatic metabolomic results showed decreased expression of reduced nicotinamide adenine dinucleotide (NADH), nicotinamide adenine dinucleotide (NAD), phosphoenolpyruvic acid (PEP), and phosphoric acid, which are involved in the glycolysis pathway. The transcriptomic results indicated that genes involved in glycolysis showed a downregulation trend. qPCR and Western blot revealed that pyruvate kinase (PKLR), the key rate-limiting enzyme in glycolysis, was significantly reduced after the deletion of the miR-23b/27b/24-1 cluster. Together, these observations suggest that the miR-23b/27b/24-1 cluster is involved in the regulation of glucose homeostasis via the glycolysis pathway.
miRNAs 的改变与许多代谢紊乱有关，如 2 型糖尿病（T2DM）。miR-23b/27b/24-1 簇包含 miR-23b、miR-27b 和 miR-24-1，它们位于 9 号染色体上的 881 bp 内。研究表明，miR-23b、miR-27b 和 miR-24-1 的作用具有多方面的功能，在各种代谢紊乱中发挥作用。然而，它们在体内代谢中的共同作用仍然难以捉摸。为了研究这个课题，我们构建了 miR-23b/27b/24-1 簇敲除（KO）小鼠。与野生型（WT）小鼠相比，KO 小鼠表现出葡萄糖耐量受损，伴随着呼吸交换率（RER）降低。这些改变在高脂肪饮食（HFD）诱导后更为明显。肝代谢组学结果显示，参与糖酵解途径的还原型烟酰胺腺嘌呤二核苷酸（NADH）、烟酰胺腺嘌呤二核苷酸（NAD）、磷酸烯醇丙酮酸（PEP）和磷酸减少。转录组学结果表明，参与糖酵解的基因呈下调趋势。qPCR 和 Western blot 显示，糖酵解的关键限速酶丙酮酸激酶（PKLR）在 miR-23b/27b/24-1 簇缺失后显著减少。综上所述，这些观察结果表明，miR-23b/27b/24-1 簇通过糖酵解途径参与葡萄糖稳态的调节。
