Regulation of C. elegans fat uptake and storage by acyl-CoA synthase-3 is dependent on NR5A family nuclear hormone receptor nhr-25.
Regulation of C. elegans fat uptake and storage by acyl-CoA synthase-3 is dependent on NR5A family nuclear hormone receptor nhr-25.
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DOI：
10.1016/j.cmet.2010.08.013
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发表时间：
2010-10-06
期刊：
影响因子：
29
通讯作者：
Ashrafi K
中科院分区：
文献类型：
--
作者：
Mullaney BC;Blind RD;Lemieux GA;Perez CL;Elle IC;Faergeman NJ;Van Gilst MR;Ingraham HA;Ashrafi K
酰基辅酶A脱氢酶对于脂质合成和分解、信号分子的产生和蛋白质的脂质修饰是重要的，突出了理解完整生物体内代谢途径的挑战。从一个C。在线虫诱变筛选中，我们发现ACS-3（一种长链酰基辅酶A合酶）的缺失导致肠脂质摄取增强、从头脂肪合成以及增大的富含中性脂质的肠贮库的积累。在这里，我们表明ACS-3在缝细胞中起作用，表皮细胞在解剖学上不同于脂肪吸收和储存的部位，并且ACS-3突变表型需要核激素受体NHR-25，这是C. elegans elegans蜕皮我们的研究结果表明，ACS-3衍生的长链脂肪酰辅酶A，可能纳入复杂的配体，如磷酸肌醇，调节NHR-25的功能，这反过来又调节内分泌程序的脂质摄取和合成。这些结果揭示了C.优美的
Acyl-CoA synthases are important for lipid synthesis and breakdown, generation of signaling molecules and lipid modification of proteins, highlighting the challenge of understanding metabolic pathways within intact organisms. From a C. elegans mutagenesis screen, we found that loss of ACS-3, a long-chain acyl-CoA synthase, causes enhanced intestinal lipid uptake, de novo fat synthesis, and accumulation of enlarged, neutral lipid rich intestinal depots. Here, we show that ACS-3 functions in seam cells, epidermal cells anatomically distinct from sites of fat uptake and storage, and that acs-3 mutant phenotypes require the nuclear hormone receptor NHR-25, a key regulator of C. elegans molting. Our findings suggest that ACS-3 derived long chain fatty acyl-CoAs, perhaps incorporated into complex ligands such as phosphoinositides, modulate NHR-25 function, which in turn regulates an endocrine program of lipid uptake and synthesis. These results reveal a link between acyl-CoA synthase function and an NR5A family nuclear receptor in C. elegans.
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影响因子：
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