Sampsonione F suppresses adipogenesis via activating p53 pathway during the mitotic clonal expansion progression of

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Dao-Wei Liu1, Yan-Song Ye2, Chao-Guang Huang1

  • 1Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Provincial Center for Research & Development of Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, PR China.

European Journal of Pharmacology
|May 8, 2022
PubMed

Insights

Sampsonione F, a novel adamantane-type polycyclic polyprenylated acylphloroglucinol (PPAP), effectively inhibits adipogenesis by arresting cell cycle progression during mitotic clonal expansion (MCE). This compound offers a potential therapeutic strategy for obesity by targeting key regulators of adipocyte differentiation.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Obesity arises from abnormal adipocyte proliferation and hypertrophy, driving related diseases.
  • Inhibiting adipocyte mitotic clonal expansion (MCE) offers a theoretical strategy for obesity prevention and treatment.
  • Polycyclic polyprenylated acylphloroglucinols (PPAPs), particularly adamantane-type, have shown potential in modulating adipogenesis.

Purpose of the Study:

  • To screen novel adamantane-type PPAPs for anti-adipogenic activity.
  • To investigate the structure-activity relationship of these compounds.
  • To elucidate the mechanism of action for potent anti-adipogenic PPAPs.

Main Methods:

  • Screening of six adamantane PPAPs for anti-adipogenesis effects in vitro.
  • Dose-dependent assessment of sampsonione F's impact on adipogenesis.
  • Analysis of gene and protein expression related to adipogenesis and cell cycle regulation (C/EBPβ, C/EBPα, PPARγ, FABP4, FAS, p27, p53, cyclins).

Main Results:

  • Sampsonione F significantly suppressed adipogenesis in a dose-dependent manner.
  • It decreased the expression of key adipogenic markers (C/EBPβ, C/EBPα, PPARγ, FABP4, FAS).
  • Sampsonione F upregulated p27 expression via p53 activation, leading to G1/S phase arrest and downregulation of cell cycle regulators.

Conclusions:

  • Sampsonione F inhibits adipogenesis by activating the p53 pathway and inducing G1/S phase arrest during MCE.
  • This study identifies a new adamantane-type PPAP with significant anti-adipogenic properties.
  • The findings enhance understanding of PPAP mechanisms in regulating adipogenesis and offer potential therapeutic leads for obesity.
Keywords:
3T3-L1AdipogenesisMitotic clonal expansionPPAPsp53

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