Inhibitory effects of Rocaglamide-A on PPARγ-driven adipogenesis through regulation of mitotic clonal expansion involving the JAK2/STAT3 pathway
- Authors
- Ha, Yoon-su; Kim, Taek-Kyong; Park, Ki-Sun; Hwang, Seonghwan; Kim, Jeongkyu; Kim, Seung-Jin
- Issue Date
- Jun-2022
- Publisher
- Elsevier B.V.
- Keywords
- Adipogenesis; Cell cycle; JAK2/STAT3; PPARγ; Rocaglamide-A
- Citation
- Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, v.1867, no.6
- Journal Title
- Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
- Volume
- 1867
- Number
- 6
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/61322
- DOI
- 10.1016/j.bbalip.2022.159148
- ISSN
- 1388-1981
1879-2618
- Abstract
- Inhibition of adipogenesis is an important strategy for obesity treatment. Rocaglamide-A (Roc-A) is a natural herbal medicine isolated from the genus Aglaia (family Meliaceae), which has a cyclopenta[b]benzofuran core structure. Roc-A exhibits various pharmacological effects against diverse human cancer cells. However, the exact role of Roc-A during adipogenesis in adipocytes has not been studied at all. In this study, we demonstrate that Roc-A is crucial for reducing adipogenesis via downregulating PPARγ transcriptional activity. Consistently, Western-blot and RT-PCR analyses clearly showed that Roc-A inhibits the expression of PPARγ target genes and lipogenic markers in a dose-dependent manner along with suppression of lipid accumulation, in both 3T3-L1 cells and mouse adipose-derived stem cells. Mechanistically, Roc-A significantly decreased STAT3 phosphorylation in a dose-dependent manner in 3T3-L1 adipocytes. In particular, we confirmed that Roc-A effectively suppressed the expression of genes involved in cell-cycle regulation, such as cyclin A, B, D1, and E1, early during mitotic clonal expansion in 3T3-L1 adipocytes, and this effect was abolished by the JAK2/STAT3 activator FGF2. Taken together, our results demonstrated that Roc-A reduces adipogenesis by inhibiting PPARγ transactivation and STAT3 phosphorylation and thus may serve as a therapeutic target in obesity. © 2022
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Natural Sciences > Department of Life Science > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/61322)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.