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聚合酶 I 和转录释放因子通过依赖于磷酸化的机制调节脂肪分解。

Polymerase I and transcript release factor regulates lipolysis via a phosphorylation-dependent mechanism.

机构信息

Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

出版信息

Diabetes. 2011 Mar;60(3):757-65. doi: 10.2337/db10-0744. Epub 2011 Jan 31.

DOI:10.2337/db10-0744
PMID:21282370
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3046836/
Abstract

OBJECTIVE

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.

RESEARCH DESIGN AND METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

目的

聚合酶 I 和转录释放因子（PTRF）在脂肪组织中高度表达，是质膜窖的结构组成部分。在这里，我们报告了 PTRF 在脂质动员中的一个新作用。

研究设计和方法

在禁食、再喂养以及给予儿茶酚胺和胰岛素后，检查了不同脂肪组织中 PTRF 的表达。在 3T3-L1 脂肪细胞中通过 PTRF 敲低和过表达以及 PTRF 磷酸化位点突变研究了 PTRF 在脂肪分解中的作用。

结果

小鼠白色脂肪组织（WAT）中 PTRF 的表达受营养状态调节，禁食时增加，再喂养后降至基线。PTRF 的表达也受到激素的调节，因为用胰岛素处理小鼠会导致表达减少，而异丙肾上腺素会增加 WAT 中的表达。操纵 PTRF 水平揭示了 PTRF 在脂肪分解中的作用。慢病毒介导的 PTRF 敲低导致异丙肾上腺素反应性甘油释放明显减弱。相反，过表达 PTRF 增强了异丙肾上腺素刺激的甘油释放。质谱分析显示 PTRF 在 WAT 中多个位点发生磷酸化。丝氨酸 42、苏氨酸 304 或丝氨酸 368 突变为丙氨酸降低了 3T3-L1 脂肪细胞中异丙肾上腺素刺激的甘油释放。

结论

我们的研究首次直接证明了 PTRF 作为脂肪分解的介体在脂肪组织中具有新的特定功能，并且还表明 PTRF 的磷酸化对于有效的脂肪动员是必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd00/3046836/0d6a871d6f3a/757fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd00/3046836/4e6389db9c53/757fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd00/3046836/b7a9e20bf9c1/757fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd00/3046836/1c4a68cbd11d/757fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd00/3046836/e991892efb01/757fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd00/3046836/0d6a871d6f3a/757fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd00/3046836/4e6389db9c53/757fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd00/3046836/b7a9e20bf9c1/757fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd00/3046836/1c4a68cbd11d/757fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd00/3046836/e991892efb01/757fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd00/3046836/0d6a871d6f3a/757fig5.jpg

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