Dimethylfumarate Suppresses Adipogenic Differentiation in 3T3-L1 Preadipocytes through Inhibition of STAT3 Activity

• DOI: 10.1371/journal.pone.0061411
• Publication Date: 2013-04-18T21:16:00Z
• Authors: Hyeon-Ji Kang; Hyun-Ae Seo; Younghoon Go; Chang Joo Oh; Nam Ho Jeoung; Keun-Gyu Park; In-Kyu Lee
• Keywords: 3T3-L1; Oil Red O

The excessive accumulation of adipocytes contributes to the development obesity and obesity-related diseases. interactions several transcription factors, such as C/EBPβ, PPARγ, C/EBPα, Nrf2, STAT3, are required for adipogenic differentiation. Dimethylfumarate (DMF), an immune modulator antioxidant, may function inhibitor STAT3 activator Nrf2. This study examined whether DMF inhibits differentiation 3T3-L1 preadipocytes by inhibiting or activating suppressed preadipocyte mature in a dose-dependent manner determined Oil Red O staining. mRNA protein levels genes, including SREBP-1c, FAS, aP2, were significantly lower DMF-treated preadipocytes. Suppression treatment resulted primarily from inhibition early stages clonal expansion during through induction G1 cell cycle arrest. Additionally, regulates cycle-related proteins, p21, pRb, cyclin D. markedly inhibited medium-induced phosphorylation transcriptional activation reporter construct composed four synthetic STAT3-response elements. Moreover, endogenous Nrf2 activity using dominant negative did not abolish DMF-induced In summary, is regulator based on its regulation factors proteins. mediated inhibition, but unlikely involve activation.