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

文献类型： 外文期刊

第一作者： Pan, Chongge

作者： Pan, Chongge;Hou, Yanting;Qian, Meiyu;Liang, Maodi;Wang, Jingzhou;Liu, Jie;Wei, Qianqian;Pan, Ziyan;Wang, Ting;Hu, Chenyu;Wang, Cuizhe;Zhang, Jun;Pan, Chongge;Hou, Yanting;Qian, Meiyu;Liang, Maodi;Wang, Jingzhou;Liu, Jie;Wei, Qianqian;Pan, Ziyan;Wang, Ting;Hu, Chenyu;Wang, Cuizhe;Zhang, Jun;Hou, Yali;Wang, Ruizhen;Bai, Xue;Yang, Chun;Chen, Hua;Wang, Ruizhen;Bai, Xue;Yang, Chun;Chen, Hua;Wang, Ruizhen;Chen, Hua;Xiang, Kun;Chen, Hua

作者机构：

关键词： Obesity; miR-548ab; Glucose metabolism; T2DM

期刊名称：JOURNAL OF GENETICS AND GENOMICS （ 影响因子：7.1； 五年影响因子：6.4 ）

ISSN： 1673-8527

年卷期： 2025 年 52 卷 2 期

页码：

收录情况： SCI

摘要： Dysregulation of microRNA (miRNA) expression following the development of obesity is closely linked to the onset of type 2 diabetes mellitus (T2DM). Identifying 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 1783 Kazakh and 1198 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 signalling 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. Copyright (c) 2024, The Authors. Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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