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Title 

Hirsutenone directly targets PI3K and ERK to inhibit adipogenesis in 3T3-L1 preadipocytes

Authors 

L Y CheongS SukN R ThimmegowdaM Y ChungH YangS G SeoB ShwethaJ E KimJ Y KwonBo Yeon KimK W Lee

Publisher 

Wiley-Blackwell

Issue Date 

2015

Citation 

Journal of Cellular Biochemistry, vol. 116, no. 7, pp. 1361-1370

Keywords 

ADIPOGENESISERKHIRSUTENONEMITOTIC CLONAL EXPANSIONPI3K

Abstract 

Adipogenesis is a key driver of the expansion of adipose tissue mass that causes obesity. Hirsutenone (HST) is an active botanical diarylheptanoid present in Alnus species. In this study, we evaluated the effects of HST on adipogenesis, its mechanisms of action and the molecular targets involved. Using Oil Red O staining, we observed that HST dose-dependently suppresses lipid accumulation during adipogenesis in 3T3-L1 preadipocytes, concomitant with a decrease in peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα) and fatty acid synthase (FAS) protein expression. This inhibitory effect was largely limited to the early stage of adipogenesis, which includes mitotic clonal expansion (MCE), as evidenced by delayed cell cycle entry of preadipocytes from G1 to S phase. Furthermore, the regulation of MCE was accompanied by suppression of phosphatidylinositol 3-kinase (PI3K) and extracellular-regulated kinase (ERK) activity. HST was also shown to bind directly to PI3K and ERK1 in a non-ATP competitive manner. Our results suggest that HST attenuates adipogenesis by directly targeting PI3K and ERK during MCE in 3T3-L1 preadipocytes, underscoring the potential therapeutic application of HST in preventing obesity. J. Cell. Biochem. 116: 1361-1370, 2015.

ISSN 

0730-2312

Link 

http://dx.doi.org/10.1002/jcb.25093

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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