1. SRY-Box Containing Gene 4 Promotes Liver Steatosis by Upregulation of SREBP-1c
- Author
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Jiejie Zhao, Die Zhang, Jie Liu, Yulu Chen, Shengjie Liao, Yuxing Wang, Guojun Shi, Yan Lu, Xi Yu, Xiaoying Li, Yang Jiao, Zhijian Zhang, Yanying Yang, Duanzhuo Li, Bin Liu, and Min Li
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Mice, Obese ,SOXC Transcription Factors ,03 medical and health sciences ,SOX4 ,Mice ,0302 clinical medicine ,Insulin resistance ,Downregulation and upregulation ,Transcription (biology) ,Internal medicine ,Nonalcoholic fatty liver disease ,Internal Medicine ,medicine ,Animals ,Humans ,Obesity ,Promoter Regions, Genetic ,Transcription factor ,Triglycerides ,Regulation of gene expression ,Gene knockdown ,Errata ,Chemistry ,medicine.disease ,Up-Regulation ,Fatty Liver ,030104 developmental biology ,Endocrinology ,Gene Expression Regulation ,Liver ,030220 oncology & carcinogenesis ,Insulin Resistance ,Sterol Regulatory Element Binding Protein 1 - 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 (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.
- Published
- 2018