Exendin-4 Attenuates Hepatic Steatosis by Promoting the Autophagy-Lysosomal Pathway

Hsin Hsien Yu, Hao Chen Wang, Mao Chih Hsieh, Ming Che Lee, Bor Chyuan Su, Yan Shen Shan

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1 引文 斯高帕斯(Scopus)


Dysregulated hepatic steatosis may lead to chronic liver inflammation and nonalcoholic steatohepatitis (NASH). Recent studies have suggested that exendin-4, a glucagon-like peptide-1 agonist, may be a promising therapeutic for hepatic steatosis and NASH. However, the molecular mechanisms underlying the antihepatic steatosis actions of exendin-4 are not fully clear. Here, we demonstrate that autophagy is activated by either palmitic acid (PA) or oleic acid (OA) in HepG2 cells, and exendin-4 further enhances the autophagy-lysosomal pathway. We show that inhibition of autophagy by shLC3 attenuates exendin-4-mediated antisteatotic activity. Furthermore, expression of a key lysosomal marker, lysosome associated membrane protein 1 (LAMP1), is upregulated in OA+exendin-4-treated cells. The colocalization of LAMP1 and LC3 puncta further suggests that autophagic flux was enhanced by the cotreatment. Based on these findings, we conclude that autophagic flux might play an important role in the antisteatotic action of exendin-4.
期刊BioMed Research International
出版狀態已發佈 - 2022

ASJC Scopus subject areas

  • 一般生物化學,遺傳學和分子生物學
  • 一般免疫學和微生物學


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