Biochanin A induces a brown-fat phenotype via improvement of mitochondrial biogenesis and activation ofAMPKsignaling in murineC3H10T1/2 mesenchymal stem cells
- Authors
- Rahman, Md. Shamim; Imran, Khan Mohammad; Hossain, Monir; Lee, Tae-Jin; Kim, Yong-Sik
- Issue Date
- Feb-2021
- Publisher
- John Wiley & Sons Inc.
- Keywords
- AMPK; biochanin A; brown-fat phenotype; 2; lipolysis; mitochondrial biogenesis
- Citation
- Phytotherapy Research, v.35, no.2, pp 920 - 931
- Pages
- 12
- Journal Title
- Phytotherapy Research
- Volume
- 35
- Number
- 2
- Start Page
- 920
- End Page
- 931
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/2073
- DOI
- 10.1002/ptr.6845
- ISSN
- 0951-418X
1099-1573
- Abstract
- In this study, we investigated the effect of Biochanin A (BioA), an O-methylated isoflavone on the brown-fat phenotype formation and on the associated thermogenic program including mitochondrial biogenesis and lipolysis in C3H10T1/2 MSCs. Our data demonstrates that Treatment with BioA in an adipogenic differentiation cocktail induced formation of brown-fat-like adipocytes from C3H10T1/2 MSCs without treatment with a known browning inducer (rosiglitazone or T3) at an early stage of differentiation. The formation of brown-fat-like adipocytes by BioA treatment was evidenced by upregulation of key thermogenic markers:Ucp1,Pgc1 alpha,Prdm16, andPpar gamma. BioA also increased the expression of beige (Cd137andFgf21) and brown (Elovl3andZic1)-specific markers. Additionally, BioA treatment promoted mitochondrial biogenesis, judging by the upregulation of genes;Cox8b,Cidea,Dio2,Sirt1,Opa1, andFis1. BioA treatment increased the amount of mitochondrial DNA and its encoded proteins: oxidative phosphorylation complexes (I-V); this change was associated with high oxygen consumption by C3H10T1/2 MSCs. A small-interfering-RNA-induced gene knockdown and experiments with dorsomorphin-driven competitive inhibition revealed that BioA exerts the thermogenic action via activation of AMPK signaling. Our study shows the mechanism of BioA-induced promotion of a brown-fat phenotype. Nonetheless, clinical research is necessary to validate BioA as a brown-fat-like signature inducer.
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Collections - College of Medicine > Department of Microbiology > 1. Journal Articles
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