Biomedicine & Pharmacotherapy (Jan 2024)

6-Gingerol regulates triglyceride and cholesterol biosynthesis to improve hepatic steatosis in MAFLD by activating the AMPK-SREBPs signaling pathway

  • Qingsong Xia,
  • Fuer Lu,
  • Yu Chen,
  • Jingbin Li,
  • Zhaoyi Huang,
  • Ke Fang,
  • Meilin Hu,
  • Yujin Guo,
  • Hui Dong,
  • Lijun Xu,
  • Jing Gong

Journal volume & issue
Vol. 170
p. 116060

Abstract

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Excessive synthesis of triglycerides and cholesterol accelerates the progression of hepatic steatosis in metabolic-associated fatty liver disease (MAFLD). However, the precise mechanism by which 6-gingerol mitigates hepatic steatosis in MAFLD model mice has yet to be fully understood. The present study observed that 6-gingerol administration exhibited significant protective effects against obesity, insulin resistance, and hepatic steatosis in mice subjected to a high-fat diet (HFD), and mitigated lipid accumulation in HepG2 cells treated with palmitate (PA). Following the hepatic lipidomic analysis, we confirmed that the AMPK-SREBPs signaling pathway as the underlying molecular mechanism by which 6-gingerol inhibited triglyceride and cholesterol biosynthesis, both in vivo and in vitro, through Western blot and immunofluorescence assay. Additionally, the application of an AMPK agonist/inhibitor further validated that 6-gingerol promoted AMPK activation by increasing the phosphorylation level of AMPK in vitro. Notably, the inhibitory effect of 6-gingerol on cholesterol biosynthesis, rather than triglyceride biosynthesis, was significantly diminished after silencing SREBP2 using a lentiviral plasmid shRNA in HepG2 cells. Our study demonstrates that 6-gingerol mitigates hepatic triglyceride and cholesterol biosynthesis to alleviate hepatic steatosis by activating the AMPK-SREBPs signaling pathway, indicating that 6-gingerol may be a potential candidate in the therapy of MAFLD.

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