SRY-Box Containing Gene 4 Promotes Liver Steatosis by Upregulation of SREBP-1c

Abstract

Obesity is usually associated with an increased risk of nonalcoholic fatty liver disease that is characterized by accumulation of excessive triglyceride (TG) in hepatocytes. However, the factors involved in the obesity-induced hepatosteatosis are poorly defined. Here, we report that SRY-box containing gene 4 (), a transcription factor that regulates cell proliferation and differentiation, plays an important role in hepatic TG metabolism. expression levels are markedly upregulated in livers of obese rodents and humans. Adenovirus-medicated overexpression of in the livers of lean mice promotes liver steatosis, whereas liver-specific knockdown of ameliorates TG accumulation and improves insulin resistance in obese mice. At the molecular level, we show that could directly control the transcription of gene through binding to its proximal promoter region. Thus, we have identified as an important component of hepatic TG metabolism.

Transcription factor SOX2 contributes to nonalcoholic fatty liver disease development by regulating the expression of the fatty acid transporter CD36

“…Among the SREBP isoforms, SREBP-1c predominantly regulates the transcription of genes participating in FFA synthesis, whereas SREBP-1a and SREBP-2 are associated with cholesterol synthesis [23]. Recently, SOX4, another member of the SOX family, has been shown to promote liver steatosis by directly regulating the transcription of SREBP-1c [24]. In the present study, the expression of SREBP-1a and SREBP-1c could not be observed, limiting our possible conclusions.…”

Apobec1 complementation factor overexpression promotes hepatic steatosis, fibrosis, and hepatocellular cancer

“…Those mRNAs revealed a trend towards the inverse patterns in A1cf -/liver (Supplemental Figure 7D). SOX4 overexpression in liver was shown to stabilize b-CATENIN, increase cell proliferation, promoting steatosis and HCC progression (29)(30)(31)(32), while SPARCL1 overexpression was correlated with tumor angiogenesis in HCC (33,34). Since SMAD9 inhibits Bone Morphogenetic Protein (BMP) signaling (34) we asked if the decreased expression of Smad9 in A1cf +/Tg liver was accompanied by changes in Bmp7 mRNA.…”

Diosgenin ameliorates palmitic acid-induced lipid accumulation via AMPK/ACC/CPT-1A and SREBP-1c/FAS signaling pathways in LO2 cells

“…Li et al showed that inhibiting SREBP-1c activity can exert an anti-hepatic steatosis effect in diet-induced obese mice [3]. The correlation between inhibition of the SREBP-1c/FAS pathway and decreased liver lipid synthesis has been well established [16–18]. Therefore, the activation of the AMPK/ACC/CPT-1A pathway and inhibition of the SREBP-1c/FAS pathways may be potential targets for screening drugs to prevent hepatic lipid accumulation.…”