Ubiquitous transcription factor YY1 promotes zebrafish liver steatosis and lipotoxicity by inhibiting CHOP-10 expression

Guor Mour Her*, Wan Yu Pai, Chi Yu Lai, Yang Wen Hsieh, Hsi Wen Pang

*此作品的通信作者

研究成果: Article同行評審

33 引文 斯高帕斯(Scopus)

摘要

The ubiquitous transcription factor Yin Yang 1 (YY1) is known to have diverse and complex cellular functions. Although relevant literature has reported that YY1 expression can induce the down-regulation of C/EBP homologous protein 10 (CHOP-10) and then allow the transactivation of certain transcription factors required for lipogenesis, similar properties of YY1 are poorly understood in animal model systems. In this study, we demonstrate hepatic lipid accumulation in YY1 transgenic zebrafish (GY). Oil-red staining cells were predominantly increased in the livers of both GY larvae and adults, indicating that YY1 functionally promoted lipid accumulation in GY livers. Molecular analysis revealed that YY1 over-expression contributed to the accumulation of hepatic triglycerides (TGs) by inhibiting CHOP-10 expression in the juvenile GY and 3 other fish cell lines; the decreased CHOP-10 expression then induced the transactivation of C/EBP-α and PPAR-γï€ expression. CHOP-10 morpholino (MO)-injected and rosiglitazone-treated G-liver larvae showed liver steatosis by transactivating PPAR-γ. PPAR-γ MO-injected, and GW9662- and astaxanthin-treated GY larvae showed no liver steatosis by inhibiting PPAR-γ. Moreover, a fatty acid (FA) accumulation and a TG decrease were found in the liver of aged GY, leading to the induction of FA-oxidizing systems that increased hepatic oxidative stress and liver damage. This study is the first to examine YY1 as a potential stimulator for GY liver steatosis and lipotoxicity.

原文English
頁(從 - 到)1037-1051
頁數15
期刊Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
1831
發行號6
DOIs
出版狀態Published - 6月 2013

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