Ginkgetin, a biflavone from Ginkgo biloba leaves, prevents adipogenesis through STAT5-mediated PPARγ and C/EBPα regulation

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Title
Ginkgetin, a biflavone from Ginkgo biloba leaves, prevents adipogenesis through STAT5-mediated PPARγ and C/EBPα regulation
Author(s)
Young Lai ChoJong Gil Park; H J Kang; Wooil Kim; Min Ji Jo; Ju Hong Jang; Min-Gi Kwon; Sungsik Kim; Sang Hyun Lee; Jangwook LeeYeon-Gu KimYoung-Jun ParkWon Kon KimKwang-Hee Bae; Byoung-Mog Kwon; S J Chung; Jeong Ki Min
Bibliographic Citation
Pharmacological Research, vol. 139, pp. 325-336
Publication Year
2019
Abstract
Adipogenesis involved in hypertrophy and hyperplasia of adipocytes is responsible for expanding the mass of adipose tissues in obese individuals. Peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα) are two principal transcription factors induced by delicate signaling pathways, including signal transducer and activator of transcription 5 (STAT5), in adipogenesis. Here, we demonstrated a novel role of ginkgetin, a biflavone from Ginkgo biloba leaves, as a STAT5 inhibitor that blocks the differentiation of preadipocytes into adipocytes. During the differentiation of 3T3-L1 cells, ginkgetin treatment during the first 2 days markedly inhibited the formation of lipid-bearing adipocytes. PPARγ and C/EBPα expression was decreased in 3T3-L1 cells during adipogenesis following ginkgetin treatment, whereas no change was observed in C/EBPβ or C/EBPδ expression. Inhibition of PPARγ and C/EBPα expression by ginkgetin occurred through the prevention of STAT5 activation during the initiation phase of adipogenesis. In addition, ginkgetin-mediated the inhibition of adipogenesis was recapitulated in the differentiation of primary preadipocytes. Lastly, we confirmed the inhibitory effects of ginkgetin on the hypertrophy of white adipose tissues from high-fat diet-fed mice. These results indicate that ginkgetin is a potential anti-adipogenesis and anti-obesity drug.
Keyword
AdipogenesisCCAAT/enhancer-binding protein α (C/EBPα)GinkgetinObesityPeroxisome proliferator-activated receptor γ(PPARγ)Signal transducer and activator of transcription 5 (STAT5)
ISSN
1043-6618
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.phrs.2018.11.027
Type
Article
Appears in Collections:
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
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