Science and Research

Leptin-dependent fat accumulation triggers autophagy in metabolic dysfunction-associated steatohepatitis model

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a metabolic syndrome characterized by increased fat storage in hepatocytes. In the hepatocytes, autophagy protects against cytotoxic stress and harmful cellular conditions. In the hepatic stellate cells (HSCs), autophagy exerts pro-fibrotic properties and promotes the release of pro-inflammatory metabolites. We investigated the modulation of autophagy as a therapeutic approach for MASLD. METHODS: Murine liver tissue and human hepatic cells were analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot. Real time fluorescence was performed to monitor the autophagy maturation process. Accumulation of fat was detected by Oil Red O staining. Collagen fibers were detected by picrosirius staining under polarized light. RESULTS: The loss of leptin in obese mice affected by metabolic dysfunction-associated steatohepatitis (MASH) promoted the over-expression of Becn1, Map1lc3b, Sqstm1, Uvrag and Prkaa1_2 and the accumulation of their proteins. The oleic acid caused an accumulation of fat, followed by the reduction of the autophagy proteins and the increase of the P-AMPK-

  • Polte, S. C. H.
  • Matono, T.
  • Okamoto, K.
  • Koda, M.
  • Ebrahimifard, A.
  • Wanzel, M.
  • Stiewe, T.
  • Wissniowski, T. T.
  • Matrood, S.
  • Di Fazio, P.

Keywords

  • Autophagy
  • leptin
  • metabolic dysfunction-associated steatohepatitis (MASH)
  • metabolic dysfunction-associated steatotic liver disease (MASLD)
  • metabolism
Publication details
DOI: 10.21037/tgh-25-17
Journal: Transl Gastroenterol Hepatol
Pages: 5 
Work Type: Original
Location: UGMLC
Disease Area: LC
Partner / Member: JLU, UMR
Access-Number: 41675316


chevron-down