Anti-obesity effects of kaempferol by inhibiting adipogenesis and increasing lipolysis in 3T3-L1 cells

J Physiol Biochem. 2019 Feb;75(1):83-88. doi: 10.1007/s13105-018-0659-4. Epub 2018 Dec 12.

Abstract

Kaempferol is a natural flavonoid widely found in fruits, vegetables, and tea. Kaempferol possesses beneficial biological properties such as anti-inflammatory and antioxidant activities. Positive energy balance during obesity correlates with a pro-inflammatory chronic state. In this context, we hypothesized that kaempferol might promote anti-obesity effects by modulating adipogenesis and lipolytic pathways. Adipocyte viability at 24, 48, and 72 h was measured by an ATP-based assay. Pre-adipocytes (day 0) or mature adipocytes (day 12) were treated with 60 μM kaempferol until day 21 to evaluate its potential anti-adipogenic and lipolytic effect, respectively. Total lipid accumulation was assessed using Oil Red O staining assay. Gene expression was measured by RT-qPCR to evaluate the effect of kaempferol on adipogenesis and lipolysis gene expression. Our results showed a dose-dependent effect of kaempferol treatment on cell viability promoting cell death at higher than 60 μM concentration. Pre-adipocytes stimulation by 60 μM kaempferol resulted in 62% adipogenesis inhibition whereas in mature adipocytes, it reduced 39% intracellular lipid accumulation. Also, 60 μM kaempferol treatment decreased Cebpa mRNA expression when compared to control cells. In contrast, Pnpla2 and Lipe gene expression were upregulated in 3T3-L1 cells incubated with 60 μM kaempferol. In summary, our results showed that kaempferol modulates adipogenic differentiation in 3T3-L1 cells by promoting downregulation of Cebpa gene expression and decreasing lipid accumulation in mature adipocytes by its positive effects on Pnpla2 and Lipe mRNA levels. Kaempferol might display an anti-obesity effect.

Keywords: Adipogenesis; Flavonoids; Kaempferol; Lipolysis; Obesity.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Adipogenesis / genetics
  • Animals
  • Anti-Obesity Agents / pharmacology*
  • Azo Compounds
  • CCAAT-Enhancer-Binding Proteins / antagonists & inhibitors
  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation
  • Kaempferols / pharmacology*
  • Lipase / genetics
  • Lipase / metabolism
  • Lipolysis / drug effects*
  • Lipolysis / genetics
  • Mice
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Anti-Obesity Agents
  • Azo Compounds
  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, mouse
  • Kaempferols
  • RNA, Messenger
  • kaempferol
  • Lipase
  • PNPLA2 protein, mouse
  • oil red O