Hurtado del Pozo Carmen, Vesperinas-García Gregorio, Rubio Miguel-Ángel, Corripio-Sánchez Ramón, Torres-García Antonio J, Obregon Maria-Jesus, Calvo Rosa María
Consejo Superior de Investigaciones Científicas y Universidad Autónoma de Madrid, Madrid, Spain.
Biochim Biophys Acta. 2011 Dec;1811(12):1194-200. doi: 10.1016/j.bbalip.2011.07.016. Epub 2011 Jul 30.
ChREBP is an essential transcription factor for lipogenesis. Its physiological role in adipose tissue has been studied only to a small extent and the control of its expression remains unknown in human adipocytes. We have studied ChREBP mRNA and protein expression levels in the liver and the omental (OM) and subcutaneous (SC) adipose tissues from obese and lean subjects, as well as in human differentiated preadipocytes. Liver and OM and SC adipose tissue biopsies were obtained from lean and obese patients. Human preadipocytes were isolated from the adipose tissues from obese patients and differentiated under adipogenic conditions. ChREBP expression levels were quantified by RT-PCR and Western blot analysis. We found opposing results in terms of ChREBP regulation in the liver and adipose samples. ChREBP increased in the liver from obese compared to lean subjects, whereas the expression decreased in both adipose tissues. The mRNAs of other adipogenic markers were checked in these tissues. The pattern of FASN was similar to the one for ChREBP, ADCY3 decreased in both adipose tissues from obese patients, AP2 decreased only in OM adipose tissue of obese patients and ATGL did not change. The levels of ChREBP mRNA and protein showed dramatic increases during the differentiation of human OM and SC preadipocytes. In conclusion, ChREBP expression has an opposite regulation in the liver and adipose tissue from obese subjects which is compatible with the increased hepatic lipogenesis and decreased adipocytic lipogenesis found in these patients. The dramatic increase of ChREBP mRNA and protein levels during preadipocyte differentiation suggests a role in adipogenesis.
碳水化合物反应元件结合蛋白(ChREBP)是脂肪生成所必需的转录因子。其在脂肪组织中的生理作用仅得到了有限的研究,并且在人类脂肪细胞中其表达的调控机制仍不清楚。我们研究了肥胖和消瘦受试者肝脏、网膜(OM)及皮下(SC)脂肪组织以及人类分化前脂肪细胞中ChREBP mRNA和蛋白的表达水平。从消瘦和肥胖患者获取肝脏、OM及SC脂肪组织活检样本。从肥胖患者的脂肪组织中分离出人类前脂肪细胞,并在成脂条件下进行分化。通过逆转录聚合酶链反应(RT-PCR)和蛋白质免疫印迹分析对ChREBP表达水平进行定量。我们发现在肝脏和脂肪样本中ChREBP的调控情况相反。与消瘦受试者相比,肥胖受试者肝脏中的ChREBP增加,而在两种脂肪组织中其表达均下降。检测了这些组织中其他成脂标志物的mRNA。脂肪酸合酶(FASN)的模式与ChREBP相似,肥胖患者的两种脂肪组织中腺苷酸环化酶3(ADCY3)均下降,肥胖患者仅在OM脂肪组织中载脂蛋白2(AP2)下降,而脂肪甘油三酯脂肪酶(ATGL)没有变化。在人类OM和SC前脂肪细胞分化过程中,ChREBP mRNA和蛋白水平显著增加。总之,肥胖受试者肝脏和脂肪组织中ChREBP表达具有相反的调控,这与这些患者肝脏脂肪生成增加和脂肪细胞脂肪生成减少相一致。前脂肪细胞分化过程中ChREBP mRNA和蛋白水平的显著增加表明其在脂肪生成中发挥作用。