Fisetin induces Sirt1 expression while inhibiting early adipogenesis in 3T3-L1 cells.
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.
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do 16419, Republic of Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center, Sungkyunkwan University, Seoul 06351, Republic of Korea.
Sang Chon
SC
Kim
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do 16419, Republic of Korea.
Yoo Hoon
YH
Kim
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do 16419, Republic of Korea.
Sung Wook
SW
Son
Department of Bioscience and Biotechnology, Sejong University, Seoul 05006, Republic of Korea.
Eun-Yi
EY
Moon
Division of Immunopharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Republic of Korea.
Suhkneung
S
Pyo
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do 16419, Republic of Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center, Sungkyunkwan University, Seoul 06351, Republic of Korea. Electronic address: shum@skku.edu.
Sung Hee
SH
Um
D041721:3T3-L1 Cells; D000107:Acetylation; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism*
D005419:Flavonoids; D044948:Flavonols; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D047495:PPAR gamma; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; C017875:fisetin
3T3-L1; Adipocyte differentiation; Fisetin; Sirt1