Polymerase I and transcript release factor regulates lipolysis via a phosphorylation-dependent mechanism.
Polymerase I and transcript release factor regulates lipolysis via a phosphorylation-dependent mechanism.
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DOI：
10.2337/db10-0744
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发表时间：
2011-03
期刊：
影响因子：
7.7
通讯作者：
Maratos-Flier E
中科院分区：
文献类型：
--
作者：
Aboulaich N;Chui PC;Asara JM;Flier JS;Maratos-Flier E
聚合酶I和转录物释放因子（PTRF）是在脂肪组织中高度表达的蛋白质，并且是小窝的不可或缺的结构组分。在这里，我们报告了PTRF在脂质动员中的新作用。PTRF的表达在不同的脂肪库的小鼠在禁食，再喂养，并在给药后的儿茶酚胺和胰岛素。在3 T3-L1脂肪细胞中PTRF敲低和PTRF磷酸化位点的过表达和突变后，研究了PTRF在脂解过程中的参与。PTRF在小鼠白色脂肪组织（WAT）中的表达受营养状态调节，在禁食期间增加，并且在再喂养后降低至基线。PTRF的表达也受到神经调节，因为用胰岛素处理小鼠导致表达减少，而异丙肾上腺素增加WAT中的表达。PTRF水平的操纵揭示了PTRF在脂解中的作用。慢病毒介导的PTRF敲低导致甘油释放响应异丙肾上腺素的显着衰减。相反，过表达PTRF增强异丙肾上腺素刺激的甘油释放。质谱分析显示PTRF在WAT的多个位点被磷酸化。丝氨酸42、苏氨酸304或丝氨酸368突变为丙氨酸可减少3 T3-L1脂肪细胞中异丙肾上腺素刺激的甘油释放。我们的研究是PTRF作为脂解介质的新型脂肪组织特异性功能的第一个直接证明，并且还表明PTRF的磷酸化是有效的脂肪动员所必需的。
Polymerase I and transcript release factor (PTRF) is a protein highly expressed in adipose tissue and is an integral structural component of caveolae. Here, we report on a novel role of PTRF in lipid mobilization. PTRF expression was examined in different adipose depots of mice during fasting, refeeding, and after administration of catecholamines and insulin. Involvement of PTRF during lipolysis was studied upon PTRF knockdown and overexpression and mutation of PTRF phosphorylation sites in 3T3-L1 adipocytes. PTRF expression in mouse white adipose tissue (WAT) is regulated by nutritional status, increasing during fasting and decreasing to baseline after refeeding. Expression of PTRF also is hormonally regulated because treatment of mice with insulin leads to a decrease in expression, whereas isoproterenol increases expression in WAT. Manipulation of PTRF levels revealed a role of PTRF in lipolysis. Lentiviral-mediated knockdown of PTRF resulted in a marked attenuation of glycerol release in response to isoproterenol. Conversely, overexpressing PTRF enhanced isoproterenol-stimulated glycerol release. Mass-spectrometric analysis revealed that PTRF is phosphorylated at multiple sites in WAT. Mutation of serine 42, threonine 304, or serine 368 to alanine reduced isoproterenol-stimulated glycerol release in 3T3-L1 adipocytes. Our study is the first direct demonstration for a novel adipose tissue–specific function of PTRF as a mediator of lipolysis and also shows that phosphorylation of PTRF is required for efficient fat mobilization.