Specific regulation of thermosensitive lipid droplet fusion by a nuclear hormone receptor pathway
Specific regulation of thermosensitive lipid droplet fusion by a nuclear hormone receptor pathway
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核激素受体途径对热敏脂滴融合的特异性调节
DOI：
10.1073/pnas.1704277114
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发表时间：
2017-08-15
影响因子：
11.1
通讯作者：
Zhang, Shaobing O.
中科院分区：
文献类型：
--
作者：
Li, Shiwei;Li, Qi;Zhang, Shaobing O.
核受体在调节人类脂肪代谢和能量产生中起重要作用。然而，许多核受体的调节功能和内源性配体仍然是未知的。在这里，我们报告，EMB-37 A1（人细胞色素P450 CYP 4V 2的直系同源物），EMB-8（人P450氧化还原酶POR的直系同源物），和EMB-12（人核受体VDR/LXR的同源物）构成了秀丽隐杆线虫的激素合成和核受体途径。该途径专门调节储存脂肪的脂滴的热敏融合。EMB-37 A1与EMB-8一起合成与7-dafachronic acid不同的亲脂性激素，7-dafachronic acid抑制EMB-12的融合促进功能。β-37A1还以β-12依赖性方式负调节高温下的耐热性和寿命。人CYP 4V 2可以替代C.优美的这一发现表明存在一种保守的CYP 4V 2-POR-核受体途径，其功能是将人类细胞中的多室脂滴转化为单室脂滴;该途径的失调可能导致致病性脂肪储存。
Nuclear receptors play important roles in regulating fat metabolism and energy production in humans. The regulatory functions and endogenous ligands of many nuclear receptors are still unidentified, however. Here, we report that CYP-37A1 (ortholog of human cytochrome P450 CYP4V2), EMB-8 (ortholog of human P450 oxidoreductase POR), and DAF-12 (homolog of human nuclear receptors VDR/LXR) constitute a hormone synthesis and nuclear receptor pathway in Caenorhabditis elegans. This pathway specifically regulates the thermosensitive fusion of fat-storing lipid droplets. CYP-37A1, together with EMB-8, synthesizes a lipophilic hormone not identical to.7-dafachronic acid, which represses the fusion-promoting function of DAF-12. CYP-37A1 also negatively regulates thermotolerance and lifespan at high temperature in a DAF-12-dependent manner. Human CYP4V2 can substitute for CYP-37A1 in C. elegans. This finding suggests the existence of a conserved CYP4V2-POR-nuclear receptor pathway that functions in converting multilocular lipid droplets to unilocular ones in human cells; misregulation of this pathway may lead to pathogenic fat storage.