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Updated: Mar 31, 2026
An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function
Published on: May 4, 2021
Fisetin induces Sirt1 expression while inhibiting early adipogenesis in 3T3-L1 cells
Sang Chon Kim1, Yoo Hoon Kim2, Sung Wook Son2
1Department 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.
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.
Insights
Fisetin, a natural compound, inhibits fat cell formation by regulating the Sirt1 protein. This epigenetic mechanism suppresses key genes involved in adipogenesis, offering potential for metabolic health.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Fisetin is a flavonol found in fruits and vegetables with known health benefits.
- Its effects on adipocyte differentiation and epigenetic regulation are not well understood.
Purpose of the Study:
- To investigate fisetin's impact on early adipocyte differentiation.
- To identify the epigenetic regulators involved in fisetin's action on adipogenic transcription factors.
Main Methods:
- Utilized 3T3-L1 cells to study adipocyte differentiation.
- Assessed lipid accumulation and gene expression (PPARγ, Sirt1).
- Performed Sirt1 depletion experiments and analyzed protein deacetylation (PPARγ, FoxO1).
Main Results:
- Fisetin inhibited lipid accumulation and PPARγ expression in 3T3-L1 cells.
- Fisetin increased Sirt1 expression, which was crucial for its inhibitory effects.
- Fisetin promoted Sirt1-mediated deacetylation of PPARγ and FoxO1, suppressing adipogenesis.
Conclusions:
- Fisetin represses adipogenesis through Sirt1 induction and epigenetic modification.
- The Sirt1-PPARγ pathway is a key target for fisetin's anti-adipogenic effects.
- Fisetin's action highlights its potential role in controlling fat cell differentiation.
