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

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

J Genet Genomics. 2024 Nov 26:S1673-8527(24)00324-2. doi: 10.1016/j.jgg.2024.11.011. Online ahead of print.

Authors

Chongge Pan¹, Yali Hou², Yanting Hou¹, Ruizhen Wang³, Meiyu Qian¹, Xue Bai⁴, Maodi Liang¹, Jingzhou Wang¹, Jie Liu¹, Qianqian Wei¹, Ziyan Pan¹, Ting Wang¹, Chenyu Hu¹, Kun Xiang⁵, Chun Yang⁴, Cuizhe Wang⁶, Hua Chen⁷, Jun Zhang⁸

Affiliations

¹ Medical College of Shihezi University, Shihezi, Xinjiang 832000, China; Laboratory of Xinjiang Endemic and Ethic Diseases of Shihezi University, Shihezi, Xinjiang 832000, China.
² Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
³ China National Center for Bioinformation, Beijing 100101, China; Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
⁴ China National Center for Bioinformation, Beijing 100101, China; Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
⁵ The First People's Hospital of Yunnan Province, Kunming, Yunnan 650223, China.
⁶ Medical College of Shihezi University, Shihezi, Xinjiang 832000, China; Laboratory of Xinjiang Endemic and Ethic Diseases of Shihezi University, Shihezi, Xinjiang 832000, China. Electronic address: wangcuizhe905@163.com.
⁷ China National Center for Bioinformation, Beijing 100101, China; Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, Yunnan 650223, China. Electronic address: chenh@big.ac.cn.
⁸ Medical College of Shihezi University, Shihezi, Xinjiang 832000, China; Laboratory of Xinjiang Endemic and Ethic Diseases of Shihezi University, Shihezi, Xinjiang 832000, China. Electronic address: zhangjunyc@163.com.

PMID: 39608671
DOI: 10.1016/j.jgg.2024.11.011

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.

Keywords: GULP1 and SLC25A21; Glucose metabolism; Obesity; T2DM; miR-548ab.