Original Research Article
Modulation of intracellular glutathione affects adipogenesis in 3T3-L1 cells
Article first published online: 25 APR 2011
Copyright © 2010 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 226, Issue 8, pages 2016–2024, August 2011
How to Cite
Vigilanza, P., Aquilano, K., Baldelli, S., Rotilio, G. and Ciriolo, M. R. (2011), Modulation of intracellular glutathione affects adipogenesis in 3T3-L1 cells. J. Cell. Physiol., 226: 2016–2024. doi: 10.1002/jcp.22542
- Issue published online: 25 APR 2011
- Article first published online: 25 APR 2011
- Accepted manuscript online: 6 DEC 2010 12:00AM EST
- Manuscript Accepted: 2 NOV 2010
- Manuscript Received: 28 JUL 2010
- Fondazione Roma
Impairment of redox homeostasis has been extensively associated with obesity, as a consequence of the chronic inflammatory state present in overweight subjects. Deregulation of glutathione (GSH), the most important non-enzymatic intracellular anti-oxidant, induces insulin resistance in mature adipocytes, but data are lacking about its effects on adipogenesis. In this report we demonstrate that during adipogenesis of 3T3-L1 cells the GSH/GSSG ratio decreases, shifting redox status towards oxidizing conditions. Moreover, we demonstrate that inhibition of GSH synthesis, obtained by treatment with L-buthionine-sulfoximine (BSO), enhances C/EBPβ LAP/LIP ratio and PPARγ expression during mitotic clonal expansion (MCE) stimulating adipogenesis. On the contrary, GSH ethyl ester (GSHest) supplementation completely abrogates this process also in the presence of BSO. GSH decrement during the first 24 h of adipogenesis is sufficient to induce higher triglyceride accumulation in differentiated adipocytes with respect to control, whereas GSHest treatment inhibits lipid droplets formation. We further demonstrate that Resveratrol (RV) could exert anti-adipogenic properties also by increasing GSH content through γ-glutamyl-cysteine ligase (GCL) induction. Overall data indicate that in pre-adipocytes the decrease of GSH accelerates adipogenesis, suggesting that the use of agents able to maintain GSH redox status in adipose tissue, such as RV, could be promising in stopping the lipogenic loop of obesity. J. Cell. Physiol. 226: 2016–2024, 2011. © 2010 Wiley-Liss, Inc.