石河子大学张君等研究人员合作发现，整合分析揭示miR-548ab促进肥胖和T2DM的发展。相关论文于2024年11月27日在线发表于国际学术期刊《遗传学报》。

研究人员表示，肥胖发展后miRNA表达的失调与T2DM的发生密切相关。识别差异表达的miRNA及其在调节葡萄糖代谢中的作用，将为肥胖引发T2DM的分子机制提供理论基础。

研究人员进行了一项包含1783名哈萨克族和1198名维吾尔族个体的全基因组关联研究，探讨了与空腹血糖（FPG）水平相关的小RNA（miRNA）。

通过对肝细胞、脂肪细胞以及肥胖和糖尿病小鼠分别施用miR-548ab模拟物和抑制剂，研究人员确定miR-548ab相关的下游信号通路。葡萄糖耐量试验和胰岛素耐量试验证实了miR-548ab对葡萄糖代谢的影响。

总体结果表明，miR-548ab在哈萨克族和维吾尔族人群中，与FPG水平和肥胖相关的2型糖尿病（T2DM）显著相关。miR-548ab–GULP1/SLC25A21–GLUT4网络对葡萄糖代谢、肥胖和T2DM具有调控作用，并成为肥胖引发T2DM的候选风险因子、潜在诊断标志物和治疗靶点。

此外，通过演化分析，研究人员将GULP1和SLC25A21的真实变异或单倍型，根据其对T2DM的遗传易感性进行了分类。miR-548ab抑制剂在肥胖和糖尿病小鼠中显示出有益的效果。

附：英文原文

Title: Integrated analysis reveals that miR-548ab promotes the development of obesity and T2DM

Author: Cuizhe Wang a b, Hua Chen d e f g, Jun Zhang a b

Issue&Volume: 2024/11/27

Abstract: Dysregulation of microRNA (miRNA) expression following the development of obesity is closely linked to the onset of type 2 diabetes mellitus (T2DM). Identification of differentially expressed miRNAs and their roles in regulating glucose metabolism will provide a theoretical foundation for the molecular mechanisms underlying obesity-induced T2DM. Here, we perform a genome-wide association study involving 5 glycolipid metabolism traits in 1,783 Kazakh and 1,198 Uyghur individuals to identify miRNAs associated with fasting plasma glucose (FPG) levels. A miR-548ab mimic and inhibitor are administered to hepatocytes and adipocytes, as well as obese and diabetic mice, to determine miR-548ab-related downstream signaling pathways. The effects of miR-548ab on glucose metabolism are validated using the glucose tolerance test and insulin tolerance test. Collectively, these results indicate that miR-548ab is significantly associated with FPG levels and obesity-related T2DM in both Kazakh and Uyghur populations. The miR-548ab–GULP1/SLC25A21–GLUT4 network exerts regulatory effects on glucose metabolism, obesity, and T2DM, positioning it as a candidate risk factor, potential diagnostic marker, and therapeutic target for obesity-induced T2DM. Additionally, through evolutionary analysis, the authentic variants or haplotypes of GULP1 and SLC25A21 are categorized according to their genetic susceptibility to T2DM. The miR-548ab inhibitor shows beneficial effects in obese and diabetic mice.

DOI: 10.1016/j.jgg.2024.11.011

Source: https://www.sciencedirect.com/science/article/pii/S1673852724003242