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

Kim, Sang Chon; Kim, Yoo Hoon; Son, Sung Wook; Moon, Eun‐Yi; Pyo, Suhkneung; Um, Sung Hee

doi:10.1016/j.bbrc.2015.10.094

Cited by 38 publications

(37 citation statements)

References 25 publications

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“…Myricetin-treated 3T3-L1 cells downregulates transcription factors such as Pparg, Cebpα, Cebpβ, Lpl, Fabp4, Glut4, and Srebp-1c. Other antiadipogenic targets of myricetin include inhibition of ERK and c-Jun N-terminal kinase (JNK) phosphorylation during the differentiation process [117]. Microarray analysis revealed that kaemperol decreases expression of adipogenic transcription factors and triglyceride synthesis-related genes and, conversely, increases gene involved in lipolysis [106].…”

Section: Flavonolsmentioning

confidence: 99%

“…It has been reported that resveratrol inhibits human preadipocyte proliferation and adipogenesis in a SIRT1-dependent manner [116]. Fisetin suppresses the early stages of adipogenesis through SIRT1-mediated deacetylation of PPARγ and FoxO1, and enhances the association of SIRT1 with the PPARγ promoter, leading to suppression of PPARγ transcriptional activity [117].…”

Section: Isoflavonesmentioning

confidence: 99%

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Differential effects of dietary flavonoids on adipogenesis

et al. 2018

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Propose Obesity is a fast growing epidemic worldwide. During obesity, the increase in adipose tissue mass arise from two different mechanisms, namely, hyperplasia and hypertrophy. Hyperplasia which is the increase in adipocyte number is characteristic of severe obese patients. Recently, there has been much interest in targeting adipogenesis as therapeutic strategy against obesity. Flavonoids have been shown to regulate several pathways and affect a number of molecular targets during specific stages of adipocyte development. Methods Presently, we provide a review of key studies evaluating the effects of dietary flavonoids in different stages of adipocyte development with a particular emphasis on the investigations that explore the underlying mechanisms of action of these compounds in human or animal cell lines as well as animal models. Results Flavonoids have been shown to regulate several pathways and affect a number of molecular targets during specific stages of adipocyte development. Although most of the studies reveal anti-adipogenic effect of flavonoids, some flavonoids demonstrated proadipogenic effect in mesenchymal stem cells or preadipocytes. Conclusion The anti-adipogenic effect of flavonoids is mainly via their effect on regulation of several pathways such as induction of apoptosis, suppression of key adipogenic transcription factors, activation of AMPK and Wnt pathways, inhibition of clonal expansion, and cell-cycle arrest.

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Section: Flavonolsmentioning

confidence: 99%

Section: Isoflavonesmentioning

confidence: 99%

Differential effects of dietary flavonoids on adipogenesis

et al. 2018

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“…Fisetin also induces SIRT1 expression and inhibits early adipogenesis in 3T3-L1 cells [45]. We found here that Tm (1 µg/mL) treatment for 16 h significantly decreased SIRT1 expression, but co-treatment with fisetin (5–20 µM) reversed the reduction (Figure 9a,b).…”

Section: Resultsmentioning

confidence: 53%

Fisetin Protects PC12 Cells from Tunicamycin-Mediated Cell Death via Reactive Oxygen Species Scavenging and Modulation of Nrf2-Driven Gene Expression, SIRT1 and MAPK Signaling in PC12 Cells

Yen

Chen

et al. 2017

IJMS

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Background: Fisetin (3,7,3′,4′-tetrahydroxyflavone) is a dietary flavonol and exhibits antioxidant, anti-inflammatory, and neuroprotective activities. However, high concentration of fisetin is reported to produce reactive oxygen species (ROS), induce endoplasmic reticulum (ER) stress and cause cytotoxicity in cancer cells. The aim of this study is to investigate the cytoprotective effects of low concentration of fisetin against tunicamycin (Tm)-mediated cytotoxicity in neuronal-like catecholaminergic PC12 cells. Methods: Cell viability was assayed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and apoptotic and autophagic markers were analyzed by Western blot. Gene expression of unfolded protein response (UPR) and Phase II enzymes was further investigated using RT-Q-PCR or Western blotting. Intracellular ROS level was measured using 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) by a fluorometer. The effects of fisetin on mitogen activated protein kinases (MAPKs) and SIRT1 (Sirtuin 1) signaling pathways were examined using Western blotting and specific inhibitors. Results: Fisetin (<20 µM) restored cell viability and repressed apoptosis, autophagy and ROS production in Tm-treated cells. Fisetin attenuated Tm-mediated expression of ER stress genes, such as glucose-regulated proteins 78 (GRP78), C/EBP homologous protein (CHOP also known as GADD153) and Tribbles homolog 3 (TRB3), but induced the expression of nuclear E2 related factor (Nrf)2-targeted heme oxygenase (HO)-1, glutamate cysteine ligase (GCL) and cystine/glutamate transporter (xCT/SLC7A11), in both the presence and absence of Tm. Moreover, fisetin enhanced phosphorylation of ERK (extracellular signal-regulated kinase), JNK (c-JUN NH2-terminal protein kinase), and p38 MAPK. Addition of JNK and p38 MAPK inhibitor significantly antagonized its cytoprotective activity and modulatory effects on UPR. Fisetin also restored Tm-inhibited SIRT1 expression and addition of sirtinol (SIRT1 activation inhibitor) significantly blocked fisetin-mediated cytoprotection. In conclusion, this result shows that fisetin activates Nrf2, MAPK and SIRT1, which may elicit adaptive cellular stress response pathways so as to protect cells from Tm-induced cytotoxicity.

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“…Herein we showed that SEs, water extracts of sigumjang prepared by fermenting barley bran, inhibit the early stage of adipocyte differentiation and late stage of lipid accumulation in 3T3-L1 cells. Prior studies have reported that the anti-adipogenic effects of several phytochemicals are related to inhibition of early adipogenic stages during differentiation (17,18).…”

Section: Effects Of Ses On Protein Expression Of Genes Involved In Admentioning

confidence: 99%

Sigumjang (fermented barley bran) water-soluble extracts inhibit the expression of adipogenic and lipogenic regulators in 3T3-L1 adipocytes

Jeong

Lee

Kim

et al. 2016

Food Sci Biotechnol

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prepared from fermented barley bran is a traditional fermented food found only in the Gyeongsang-do area of South Korea. There have been no studies reported to date despite the potential bioactivities of . In this study, the anti-obesity activities of extracts (SEs) during 3T3-L1 differentiation into adipocytes were investigated. SEs inhibited adipocyte differentiation by suppressing the CCAAT/enhancer binding protein-β and sterol regulatory element binding protein-1c expression in the early stage of differentiation, followed by the suppression of the peroxisome proliferator-activated receptor-γ, CCAAT/enhancer binding protein-α, and adiponectin. These changes in adipogenic markers induced inhibition of lipogenesis via down-regulation of mainly fatty acid synthase, acetyl-CoA carboxylase, fatty acid binding protein 4, and perilipin. These results were more significant in the extract of fermented with isolated MFST compared to naturally fermented group. SEs can be considered as a useful material for developing food with health benefits and anti-obesity properties.

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

Cited by 38 publications

References 25 publications

Differential effects of dietary flavonoids on adipogenesis

Differential effects of dietary flavonoids on adipogenesis

Fisetin Protects PC12 Cells from Tunicamycin-Mediated Cell Death via Reactive Oxygen Species Scavenging and Modulation of Nrf2-Driven Gene Expression, SIRT1 and MAPK Signaling in PC12 Cells

Sigumjang (fermented barley bran) water-soluble extracts inhibit the expression of adipogenic and lipogenic regulators in 3T3-L1 adipocytes

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