Apigetrin inhibits adipogenesis in 3T3-L1 cells by downregulating PPARγ and CEBP-α

Lipids Health Dis. 2018 Apr 25;17(1):95. doi: 10.1186/s12944-018-0738-0.

Abstract

Background: Apigetrin, a flavonoid found in many plant leaves and seeds, has been known to possess antimutagenic, anti-cancer, antioxidant and anti-inflammatory properties. Here, we are investigating the effect of the apigetrin on adipocytes differentiation in 3T3-L1 adipocytes, and elucidating the mechanism of its action.

Methods: Lipids accumulation was measured by Oil Red O staining and cell cycle was analyzed by flow cytometry. The antioxidant effect of apigetrin was evaluated against hydrogen peroxide. The expression of various genes, involved in adipogenesis and inflammation, was studied by real-time PCR.

Results: Our results showed that apigterin treatment inhibited significantly lipid accumulation without effect on cell viability at 100 μM, and it exerted the anti-adipogenic effect during the early stages of differentiation. Flow cytometry analysis showed that apigenin-7-O-glucoside (Ap7G) inhibited cell proliferation during mitotic clonal expansion and caused cell cycle delay. Quantitative PCR analysis revealed that the mRNA levels of C/EBP-α, PPAR-γ, SREBP-1c and FAS were suppressed after apigetrin treatment at 100 μM. Moreover, the mRNA level of pro-inflammatory genes (TNF-α and IL-6) were suppressed after apigterin treatment, at high concentration preadipocyte cells.

Conclusion: Taken together, these results indicated that apigenin-7-O-glucoside inhibits adipogenesis of 3T3-L1 preadipocytes at early stage of adipogenesis.

Keywords: Adipogenesis; Apigetrin; Cell cycle; IL-6; ROS; TNF-α.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Adipogenesis / genetics
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Apigenin / pharmacology*
  • CCAAT-Enhancer-Binding Proteins / antagonists & inhibitors
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Cell Differentiation / drug effects
  • Gene Expression Regulation
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Mice
  • PPAR gamma / antagonists & inhibitors
  • PPAR gamma / genetics*
  • PPAR gamma / metabolism
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Sterol Regulatory Element Binding Protein 1 / antagonists & inhibitors
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • fas Receptor / antagonists & inhibitors
  • fas Receptor / genetics
  • fas Receptor / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, mouse
  • Fas protein, mouse
  • Interleukin-6
  • PPAR gamma
  • RNA, Messenger
  • Srebf1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • interleukin-6, mouse
  • apigetrin
  • Apigenin