Ascochlorin Attenuates the Early Stage of Adipogenesis via the Wnt/β-Catenin Pathway and Inhibits High-Fat-Diet-Induced Obesity in Mice

Int J Mol Sci. 2024 Sep 23;25(18):10226. doi: 10.3390/ijms251810226.

Abstract

This study investigated the effects of ascochlorin (ASC), a natural compound derived from the fungus Ascochyta viciae, on adipogenesis and obesity. We determined the effects of ASC on 3T3-L1 preadipocytes and whether it ameliorated to mitigate high-fat diet (HFD)-induced obesity in C57BL/6J mice. We found that ASC significantly inhibited the differentiation of preadipocytes by modulating the Wnt/β-catenin signaling pathway, a key regulator of adipogenic processes. Treatment with ASC not only reduced the mRNA and protein expression of key adipogenic transcription factors such as C/EBPα and PPARγ, but also reduced lipid accumulation both in vitro and in vivo. In addition, treatment HFD-fed mice with ASC significantly reduced their weight gain and adiposity vs. control mice. These results suggest that ASC has considerable potential as a therapeutic agent for obesity, owing to its dual action of inhibiting adipocyte differentiation and reducing lipid accumulation. Thus, ASC represents a promising candidate as a natural anti-obesity agent.

Keywords: adipogenesis; ascochlorin; high-fat diet; obesity; β-catenin.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes* / drug effects
  • Adipocytes* / metabolism
  • Adipogenesis* / drug effects
  • Alkenes
  • Animals
  • Anti-Obesity Agents / pharmacology
  • Cell Differentiation / drug effects
  • Diet, High-Fat* / adverse effects
  • Lipid Metabolism / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity* / drug therapy
  • Obesity* / etiology
  • Obesity* / metabolism
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Phenols / pharmacology
  • Wnt Signaling Pathway* / drug effects
  • beta Catenin / metabolism

Substances

  • Alkenes
  • Anti-Obesity Agents
  • ascochlorin
  • beta Catenin
  • Phenols
  • PPAR gamma