Postic Catherine, Dentin Renaud, Denechaud Pierre-Damien, Girard Jean
Département d'Endocrinologie, Métabolisme et Cancer, Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France.
Annu Rev Nutr. 2007;27:179-92. doi: 10.1146/annurev.nutr.27.061406.093618.
Dysregulations in hepatic lipid synthesis are often associated with obesity and type 2 diabetes, and therefore a perfect understanding of the regulation of this metabolic pathway appears essential to identify potential therapeutic targets. Recently, the transcription factor ChREBP (carbohydrate-responsive element-binding protein) has emerged as a major mediator of glucose action on lipogenic gene expression and as a key determinant of lipid synthesis in vivo. Indeed, liver-specific inhibition of ChREBP improves hepatic steatosis and insulin resistance in obese ob/ob mice. Since ChREBP cellular localization is a determinant of its functional activity, a better knowledge of the mechanisms involved in regulating its nucleo-cytoplasmic shuttling and/or its post-translational activation is crucial in both physiology and physiopathology. Here, we review some of the studies that have begun to elucidate the regulation and function of this key transcription factor in liver.
肝脏脂质合成的失调常与肥胖和2型糖尿病相关，因此，全面了解这一代谢途径的调控对于确定潜在的治疗靶点似乎至关重要。最近，转录因子ChREBP（碳水化合物反应元件结合蛋白）已成为葡萄糖对脂肪生成基因表达作用的主要调节因子，以及体内脂质合成的关键决定因素。事实上，在肥胖的ob/ob小鼠中，肝脏特异性抑制ChREBP可改善肝脂肪变性和胰岛素抵抗。由于ChREBP的细胞定位是其功能活性的决定因素，更好地了解调节其核质穿梭和/或翻译后激活的机制在生理学和病理生理学中都至关重要。在这里，我们综述了一些已开始阐明这一关键转录因子在肝脏中的调控和功能的研究。
