Liraglutide induces beige fat development and promotes mitochondrial function in diet induced obesity mice partially through AMPK-SIRT-1-PGC1-α cell signaling pathway

Joseph Zhou, Anil Poudel, Prashanth Chandramani-Shivalingappa, Biao Xu, Ryan Welchko, Lixin Li

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Purpose: Glucagon like peptide-1 (GLP-1) is produced to induce postprandial insulin secretion. Liraglutide, a full agonist of the GLP-1 receptor, has a protective effect on weight gain in obese subjects. Brown adipose tissue plays a major role in the control of energy balance and is known to be involved in the weight loss regulated by liraglutide. The putative anti-obesity properties of liraglutide and the cell signaling pathways involved were examined. Methods: Four groups of C57/BL6 mice fed with chow or HFHS diet were injected with either liraglutide or vehicle for four weeks. Western blotting was used to analyze protein expression. Results: Liraglutide significantly attenuated the weight gain in mice fed with HFHS diet and was associated with significant reductions of epididymal fat and inguinal fat mass. Furthermore, liraglutide significantly upregulated the expression of brown adipose-specific markers in perigonadal fat in association with upregulation of AMPK-SIRT-1-PGC1-α cell signaling. However, elevation of brown fat markers in skeletal muscle was only observed in HFHS diet fed mice after liraglutide treatment, and AMPK-SIRT-1 cell signaling is not involved in this process. Conclusions: the anti-obesity effect of liraglutide occurs through adaptive thermogenesis and may act through different cell signaling pathways in fat and skeletal muscle tissue. Liraglutide induces beige fat development partially through the AMPK-SIRT-1-PGC1-α cell signaling pathway. Therefore, liraglutide is a potential medication for obesity prevention and in targeting pre-diabetics.

Original languageEnglish
Pages (from-to)271-283
Number of pages13
JournalEndocrine
Volume64
Issue number2
DOIs
StatePublished - May 15 2019

Keywords

  • Beige fat
  • Diet induced obesity
  • Insulin resistance
  • Liraglutide

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