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Updated: Jun 16, 2025

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
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Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy

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GLP-1RAs regulate lipid metabolism and induce autophagy through AMPK/SIRT1 pathway to improve NAFLD

Qiang Zhang1, Jingyuan Wang2, Xiaojin Hu3

  • 1Department of Gastroenterology, Yancheng Third People's Hospital (The Yancheng School of Clinical Medicine of Nanjing Medical University), Yancheng, Jiangsu Province 224000, PR China.

Prostaglandins & Other Lipid Mediators
|April 3, 2025
PubMed
Abstract

Insights

Liraglutide reverses fatty liver in hepatocytes by regulating lipid metabolism and enhancing autophagy. This action occurs through the AMPK/SIRT1 pathway, offering a new therapeutic target for non-alcoholic fatty liver disease.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Endocrinology

Background:

  • Non-alcoholic fatty liver disease (NAFLD) is a significant cause of cirrhosis and liver-related mortality.
  • Current treatments for NAFLD are limited, necessitating exploration of novel therapeutic agents.
  • Glucagon-like peptide-1 receptor agonists (GLP-1RAs) show potential for NAFLD treatment, but their mechanisms require elucidation.

Purpose of the Study:

  • To investigate the therapeutic effect of liraglutide (LRG), a GLP-1RA, on hepatic steatosis.
  • To determine if LRG's effect on NAFLD involves regulating lipid metabolism and enhancing autophagy in hepatocytes.
  • To elucidate the specific molecular pathways, including AMPK/SIRT1 signaling, involved in LRG's action.

Main Methods:

  • Examined LRG's effect on fat accumulation in fatty hepatocytes.
  • Assessed LRG's impact on enzymes regulating lipid metabolism and autophagy.
  • Utilized SIRT1 knockdown in free fatty acid (FFA)-treated cells to investigate LRG's mechanism via AMPK/SIRT1 signaling.

Main Results:

  • LRG significantly reversed FFA-induced hepatocyte steatosis.
  • LRG modulated the expression of key proteins involved in lipogenesis and lipolysis (FAS, ACC1, ATGL, HSL, LAL).
  • LRG enhanced autophagy, increased SIRT1 expression, and reduced lipid accumulation in an AMPK-dependent manner, with SIRT1 knockdown diminishing these effects.

Conclusions:

  • GLP-1RAs, like LRG, may treat hepatic steatosis by modulating lipid metabolism and autophagy.
  • The AMPK/SIRT1 pathway is crucial for the therapeutic effects of LRG on NAFLD.
  • These findings suggest GLP-1RAs as a promising therapeutic strategy for NAFLD.
Keywords:
AMPK/SIRT1 pathwayAutophagyGLP-1RAsNAFLD

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