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

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

doi:10.1016/j.jgg.2024.11.011

Volume 52 Issue 2

Feb. 2025

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

doi: 10.1016/j.jgg.2024.11.011

Chongge Pan^a,b,
Yali Hou^c,
Yanting Hou^a,b,
Ruizhen Wang^d,e,f,
Meiyu Qian^a,b,
Xue Bai^d,e,
Maodi Liang^a,b,
Jingzhou Wang^a,b,
Jie Liu^a,b,
Qianqian Wei^a,b,
Ziyan Pan^a,b,
Ting Wang^a,b,
Chenyu Hu^a,b,
Kun Xiang^g,
Chun Yang^d,e,
Cuizhe Wang^a,b,
Hua Chen^d,e,f,h,
Jun Zhang^a,b

a. Medical College of Shihezi University, Shihezi, Xinjiang 832000, China;
b. Laboratory of Xinjiang Endemic and Ethic Diseases of Shihezi University, Shihezi, Xinjiang 832000, China;
c. Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China;
d. China National Center for Bioinformation, Beijing 100101, China;
e. Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China;
f. University of Chinese Academy of Sciences, Beijing 100049, China;
g. The First People's Hospital of Yunnan Province, Kunming, Yunnan 650223, China;
h. Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, Yunnan 650223, China

Received Date: 2024-06-07
Accepted Date: 2024-11-17
Rev Recd Date: 2024-11-16

Available Online: 2025-07-11

Publish Date: 2024-11-27

Abstract

Abstract

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.
- Obesity,
- miR-548ab,
- GULP1 and SLC25A21,
- Glucose metabolism,
- T2DM

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