Fisetin induces Sirt1 expression while inhibiting early adipogenesis in 3T3-L1 cells

Biochem Biophys Res Commun. 2015 Nov 27;467(4):638-44. doi: 10.1016/j.bbrc.2015.10.094. Epub 2015 Oct 21.

Abstract

Fisetin (3,7,3',4'-tetrahydroxyflavone) is a naturally found flavonol in many fruits and vegetables and is known to have anti-aging, anti-cancer and anti-viral effects. However, the effects of fisetin on early adipocyte differentiation and the epigenetic regulator controlling adipogenic transcription factors remain unclear. Here, we show that fisetin inhibits lipid accumulation and suppresses the expression of PPARγ in 3T3-L1 cells. Fisetin suppressed early stages of preadipocyte differentiation, and induced expression of Sirt1. Depletion of Sirt1 abolished the inhibitory effects of fisetin on intracellular lipid accumulation and on PPARγ expression. Mechanistically, fisetin facilitated Sirt1-mediated deacetylation of PPARγ and FoxO1, and enhanced the association of Sirt1 with the PPARγ promoter, leading to suppression of PPARγ transcriptional activity, thereby repressing adipogenesis. Lowering Sirt1 levels reversed the effects of fisetin on deacetylation of PPARγ and increased PPARγ transactivation. Collectively, our results suggest the effects of fisetin in increasing Sirt1 expression and in epigenetic control of early adipogenesis.

Keywords: 3T3-L1; Adipocyte differentiation; Fisetin; Sirt1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Acetylation
  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Animals
  • Cell Differentiation / drug effects
  • Flavonoids / pharmacology*
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors / metabolism
  • Lipid Metabolism
  • Mice
  • PPAR gamma / metabolism
  • Sirtuin 1 / metabolism*

Substances

  • Flavonoids
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Foxo1 protein, mouse
  • PPAR gamma
  • Sirt1 protein, mouse
  • Sirtuin 1
  • fisetin