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Mechanistic insights into GLP-1 receptor agonist-induced weight loss through ceRNA network analysis

Wenxin Li1, Xinyu Zhang2, Jiamin Song1

  • 1Department of Endocrinology and Metabolism, The Affiliated Hospital of Jiangsu University, Institute of Endocrine and Metabolic Diseases, Jiangsu University, Zhenjiang 212000, Jiangsu, China.

Genomics
|January 6, 2025
PubMed
Abstract

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1RA) may promote weight loss by activating PI3K-Akt and AMPK pathways. This involves a competing endogenous RNA (ceRNA) network of circular RNAs (circRNAs) influencing lipid metabolism in obesity.

Area of Science:

  • Molecular Biology
  • Genomics
  • Metabolic Research

Background:

  • Glucagon-like peptide-1 receptor agonists (GLP-1RA) are established treatments for obesity.
  • Circular RNAs (circRNAs) are implicated in obesity pathogenesis.
  • The precise role of circRNAs in GLP-1RA-mediated weight loss is not well understood.

Purpose of the Study:

  • To investigate the molecular mechanisms by which circRNAs contribute to GLP-1RA-induced weight loss.
  • To elucidate the circRNA-miRNA-mRNA regulatory network involved in obesity and GLP-1RA treatment.

Main Methods:

  • High-throughput sequencing of epididymal adipose tissue from obese mice treated with GLP-1RA.
  • Differential expression analysis of circRNAs, miRNAs, and mRNAs.
  • Construction and analysis of a circRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network.
  • KEGG pathway enrichment analysis and Western blotting validation.

Main Results:

  • Identification of numerous differentially expressed circRNAs, miRNAs, and mRNAs.
  • The ceRNA network analysis revealed enrichment in lipid and fatty acid metabolism pathways.
  • Key pathways implicated include PI3K-Akt and AMPK signaling.
  • GLP-1RA treatment led to increased AKT and AMPK phosphorylation, reducing SREBP-1, ACC, and FAS expression.

Conclusions:

  • GLP-1RA may exert anti-obesity effects by activating PI3K-Akt and AMPK signaling pathways.
  • This activation appears to be mediated through a circRNA-based ceRNA network.
  • These findings provide novel insights into the molecular underpinnings of GLP-1RA action in obesity.
Keywords:
AMPK signaling pathwayCompeting endogenous RNA networkGLP-1 receptor agonistObesityPI3K-Akt signaling pathway

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