Abstract
Promoting non-trembling thermogenesis of brown adipose tissue (BAT) and browning of white adipose tissue (WAT) helps prevent obesity. MiR-23b is highly expressed in adipose tissue-derived exosomes obtained from obese people, but the role of exosomal miR-23b in regulating thermogenesis and obesity progression remains to be further explored. Here, a mouse obesity model was established through high-fat diet (HFD), and inguinal WAT (iWAT)-derived exosomes and miR-23b antagomir were administered by intraperitoneal injection. The results showed that WAT-derived exosomal miR-23b upregulated body weight and adipocyte hypertrophy and enhanced insulin resistance. Moreover, exosomal miR-23b restrained mtDNA copy number and the expression of genes related to thermogenesis and mitochondrial biogenesis in BAT, and suppressed the expression of WAT browning-related genes under cold stimulation, indicating that exosomal miR-23b hindered non-trembling thermogenesis of BAT and WAT browning. Mechanism studies found that miR-23b targeted Elf4 to inhibit its expression. And Elf4 bound to the GLP-1R promoter region to promote GLP-1R transcription. In addition, silencing miR-23b effectively abolished the inhibitory effect of WAT-derived exosomes on thermogenic gene expression and mitochondrial respiration in adipocytes isolated from BAT and iWAT, which was reversed by GLP-1R knockdown. In conclusion, WAT-derived exosomal miR-23b suppressed thermogenesis by targeting Elf4 to regulate GLP-1R transcription, which contributed to the progression of obesity.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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This work was supported by the General project of Shaanxi Provincial Department of Science and Technology (2020JM609).
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The authors declare that all data were generated in-house and that no paper mill was used. Q.W. designed this work and wrote the manuscript, performed the experiments. R.M. collected and analyzed the data. J.D. organized the figures. All authors reviewed the manuscript.
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Wang, Q., Du, J. & Ma, R. White adipocyte-derived exosomal miR-23b inhibits thermogenesis by targeting Elf4 to regulate GLP-1R transcription. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-02984-1
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DOI: https://doi.org/10.1007/s00210-024-02984-1