Wenxin Li , Xinyu Zhang , Jiamin Song , Ling Yang , Dong Wang , Guoyue Yuan , Li Zhao
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Mechanistic insights into GLP-1 receptor agonist-induced weight loss through ceRNA network analysis
Background
GLP-1 receptor agonists (GLP-1RA) have been extensively utilized in the management of body weight in individuals with obesity. Circular RNA (circRNA), a class of covalently closed RNA molecules, has garnered increasing attention for its potential role in the pathogenesis of obesity. However, the specific mechanisms through which circRNA contributes to GLP-1RA-induced weight loss remains elusive.
Methods
High-throughput sequencing analyzed epididymal adipose tissue from obese mice under high-fat, and GLP-1RA intervention (600 μg/kg/d). The functions of differentially expressed (DE) genes were enriched and analyzed. The circRNA-miRNA-mRNA interaction network was constructed in Cytoscape, and KEGG pathway gene enrichment was validated via western blotting.
Results
A total of 644 DEcircRNAs, 186 DEmiRNAs, and 3474 DEmRNAs were identified. Based on ceRNA score calculations, network diagrams were constructed. Gene Ontology (GO) analysis revealed that DERNAs were linked to lipid and fatty acid metabolism. DE genes within ceRNA pairs were enriched in lipid metabolism pathways, especially the PI3K-Akt and AMPK signaling pathways. GLP-1RA induced the phosphorylation of AKT and AMPK, which subsequently led to a reduction of SREBP-1, ACC, and FAS.
Conclusion
GLP-1RA might activate PI3K-Akt and AMPK signaling pathways to combat obesity through the ceRNA network of circRNAs.
期刊介绍：
Genomics is a forum for describing the development of genome-scale technologies and their application to all areas of biological investigation.
As a journal that has evolved with the field that carries its name, Genomics focuses on the development and application of cutting-edge methods, addressing fundamental questions with potential interest to a wide audience. Our aim is to publish the highest quality research and to provide authors with rapid, fair and accurate review and publication of manuscripts falling within our scope.
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