SRY-Box Containing Gene 4 Promotes Liver Steatosis by Upregulation of SREBP-1c.
Yang JiaoJiejie ZhaoZhijian ZhangMin LiXi YuYanying YangJie LiuShengjie LiaoDuanzhuo LiYuxing WangDie ZhangYulu ChenGuojun ShiBin LiuYan LuXiaoying LiPublished in: Diabetes (2018)
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 (Sox4), a transcription factor that regulates cell proliferation and differentiation, plays an important role in hepatic TG metabolism. Sox4 expression levels are markedly upregulated in livers of obese rodents and humans. Adenovirus-medicated overexpression of Sox4 in the livers of lean mice promotes liver steatosis, whereas liver-specific knockdown of Sox4 ameliorates TG accumulation and improves insulin resistance in obese mice. At the molecular level, we show that Sox4 could directly control the transcription of SREBP-1c gene through binding to its proximal promoter region. Thus, we have identified Sox4 as an important component of hepatic TG metabolism.
Keyphrases
- transcription factor
- genome wide identification
- high fat diet induced
- insulin resistance
- cell proliferation
- dna binding
- weight loss
- metabolic syndrome
- type diabetes
- copy number
- poor prognosis
- weight gain
- stem cells
- genome wide
- adipose tissue
- high fat diet
- signaling pathway
- bariatric surgery
- skeletal muscle
- binding protein
- cell cycle
- drug induced
- oxidative stress
- body mass index
- single molecule