Oxidative stress induced lipid accumulation via SREBP1c activation in HepG2 cells

Abstract

SREBP1c (sterol regulatory element-binding protein 1c) is a metabolic-syndrome-associated transcription factor that controls fatty acid biosynthesis under glucose/insulin stimulation. Oxidative stress increases lipid accumulation, which promotes the generation of reactive oxygen species (ROS). However, we know little about the role of oxidative stress in fatty acid biosynthesis. To clarify the action of oxidative stress in lipid accumulation via SREBP1c, we examined SREBP1c activity in H2O2-treated mammalian cells. We introduced a luciferase reporter plasmid carrying the SREBP1c-binding site into HepG2 or COS-7 cells. With increasing H2O2 dose, SREBP1c transcriptional activity increased in HepG2 cells but declined in COS-7 cells. RT-PCR analysis revealed that mRNA expression of SREBP1c gene or of SREBP1c-regulated genes rose H2O2 dose-dependently in HepG2 cells but dropped in COS-7 cells. Lipid accumulation and levels of the nuclear form of SREBP1c increased in H2O2-stimulated HepG2 cells. ROS may stimulate lipid accumulation in HepG2 cells via SREBP1c activation.

Chinese Herbal Medicine Yi-Gan-San Decreases the Lipid Accumulation in Mouse 3T3-L1 Adipocytes by Modulating the Activities of Transcription Factors SREBP-1c and FoxO1

“…4). Furthermore, we and other groups previously revealed that ROS promote lipid accumulation by stimulating SREBP-1c activity (Kohjima et al 2007;Sekiya et al 2008). These findings suggest that the anti-oxidative activity of YGS may have led to the suppression of SREBP-1c transcriptional activity.…”

“…In patients with lipid metabolic disorder, Reactive Oxygen Species (ROS) level in the blood is a little higher than normal people (Mecocci et al 2002;Potenza et al 2009). We have reported that ROS promotes lipid accumulation through the activation of SREBP-1c (Sekiya et al 2008). Therefore, we focused on SREBP-1c as a key factor for understanding the mechanism of lipid metabolic disease.…”

(−) Epigallocatechin gallate suppresses the differentiation of 3T3-L1 preadipocytes through transcription factors FoxO1 and SREBP1c

“…It is known that SREBP is activated by Akt, and it regulates the expression of cholesterol and fatty acid synthetic enzymes (Hua et al 1993). We also showed that ROSs induce SREBP1c transcriptional activity (Sekiya et al 2008). These findings indicate that the antioxidant effect of EGCG possibly reduces the transcriptional activity of SREBP1c.…”

“…In addition, activated SREBP also promotes the expression of glucose and fatty acid synthesis enzymes. We also revealed the fact that ROSs accelerate SREBP1c transcriptional activity (Sekiya et al 2008). …”

Modification in Oxidative Stress, Inflammation, and Lipoprotein Assembly in Response to Hepatocyte Nuclear Factor 4α Knockdown in Intestinal Epithelial Cells

“…A transcriptome study of the acute phase response to LPS in vivo reported a coordinate decrease of cholesterogenic gene expression (100). On the other hand, oxidative stress increased lipid hepatic lipogenesis by stimulating LXR␣ and SREBP-1c in HepG2 cells (101,102). Moreover, in livers of glutathione-deficient rats, lower mRNA abundance of SREBP-1c was detected (103), whereas in enterocytes, TNF␣ treatment induced MTP protein and SREBP-1c protein and mRNA levels (104).…”