期刊
PHARMACOLOGICAL RESEARCH
卷 139, 期 -, 页码 325-336出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2018.11.027
关键词
Ginkgetin; Peroxisome proliferator-activated receptor gamma(PPAR gamma); CCAAT/enhancer-binding protein alpha (C/EBP alpha); Signal transducer and activator of transcription 5 (STAT5); Adipogenesis; Obesity
资金
- Korea Research Institute of Bioscience and Biotechnology
- National Research Foundation of Korea - Ministry of Science, Information & Communication Technology and Future Planning [NRF-2015M3A9C4070489, NRF-2012M3A9C4048775, NRF-2017M3A9C4065954]
- Creative Allied Project through the National Research Council of Science and Technology
Adipogenesis involved in hypertrophy and hyperplasia of adipocytes is responsible for expanding the mass of adipose tissues in obese individuals. Peroxisome proliferator-activated receptor gamma (PPAR gamma) and CCAAT/enhancer-binding protein alpha (C/EBP alpha) 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. PPAR gamma and C/EBP alpha expression was decreased in 3T3-L1 cells during adipogenesis following ginkgetin treatment, whereas no change was observed in C/EBP beta or C/EBP delta expression. Inhibition of PPAR gamma and C/EBP alpha 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.
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