Reduction of lipid accumulation in HepG2 Cells by luteolin is associated with activation of AMPK and Mitigation of oxidative stress
Article first published online: 5 OCT 2010
Copyright © 2010 John Wiley & Sons, Ltd.
Volume 25, Issue 4, pages 588–596, April 2011
How to Cite
Liu, J.-F., Ma, Y., Wang, Y., Du, Z.-Y., Shen, J.-K. and Peng, H.-L. (2011), Reduction of lipid accumulation in HepG2 Cells by luteolin is associated with activation of AMPK and Mitigation of oxidative stress. Phytother. Res., 25: 588–596. doi: 10.1002/ptr.3305
- Issue published online: 25 MAR 2011
- Article first published online: 5 OCT 2010
- Manuscript Accepted: 24 AUG 2010
- Manuscript Revised: 15 JUL 2010
- Manuscript Received: 4 JAN 2010
- reactive oxygen species
The present study was carried out to investigate the lipid-lowering effect of luteolin by using a cell model of steatosis induced by palmitate. Incubation of HepG2 cells with palmitate markedly increased lipid accumulation (Oil Red O staining), the genes involved in lipogenesis, including fatty acid synthase (FAS) and its upstream regulator sterol regulatory element binding protein 1c (SREBP-1c), and reactive oxygen species (ROS) production. Luteolin enhanced the phosphorylation of AMP-activated protein kinase α (AMPKα) and its primary downstream targeting enzyme, acetyl-CoA carboxylase (ACC), up-regulated gene expression of carnitine palmitoyl transferase 1 (CPT-1), which is the rate-limiting enzyme in mitochondrial fatty acid β-oxidation, and down-regulated SREBP-1c and FAS mRNA levels in the absence and presence of palmitate. In addition, luteolin significantly decreased ROS production and ameliorated lipid accumulation in HepG2 cells caused by palmitate. Furthermore, intracellular triglyceride (TG) measurement indicated that the luteolin-mediated reduction of enhanced TG caused by palmitate was blocked by pretreatment with the AMPK inhibitor, compound C. The results suggested that the lipid-lowering effect of luteolin might be partially mediated by the up-regulation of CPT-1 and down-regulation of SREBP-1c and FAS gene expression, possibly by activation of the AMPK signaling pathway, and partially might be through its antioxidative actions. Copyright © 2010 John Wiley & Sons, Ltd.