脂质结合蛋白 5 在秀丽隐杆线虫脂肪代谢中的新功能。
Novel functions of lipid-binding protein 5 in Caenorhabditis elegans fat metabolism.
机构信息
Department of Biochemistry and Biomedical Science, World Class University Program, College of Life Science and Biotechnology, Yonsei Proteome Research Center, Yonsei University, Seoul 120-749, Korea.
出版信息
J Biol Chem. 2011 Aug 12;286(32):28111-8. doi: 10.1074/jbc.M111.227165. Epub 2011 Jun 22.
Abstract
The lipid-binding protein (LBP) family is conserved from Caenorhabditis elegans to mammals and essential for fatty acid homeostasis. RNAi-mediated knockdown of nine C. elegans lbp family members revealed that lbp-5 regulates fat accumulation. C. elegans LBP-5 bound directly to various fatty acids with varying affinities. lbp-5 expression in nhr-49(nr2041) worms was much lower than in N2 worms. Nhr-49 transcriptional activity also decreased with lbp-5 deletion, suggesting that they may work together as functional partners in fat metabolism. In support of this notion, LBP-5 translocated into nuclei, where it appeared to influence C. elegans NHR-49 target genes involved in energy metabolism. Interestingly, LBP-5 is required for stearic acid-induced transcription of NHR-49 target genes. Thus, this knowledge could help identify therapeutic targets to treat obesity and diseases associated with nematode-host interactions.
摘要
脂质结合蛋白 (LBP) 家族在从秀丽隐杆线虫到哺乳动物的生物中是保守的，对于脂肪酸的动态平衡至关重要。通过 RNAi 介导的秀丽隐杆线虫中 9 个 LBP 家族成员的敲低发现，lbp-5 调节脂肪积累。秀丽隐杆线虫 LBP-5 可以直接结合各种脂肪酸，亲和力不同。nhr-49(nr2041) 线虫中的 lbp-5 表达水平远低于 N2 线虫。nhr-49 的转录活性也随着 lbp-5 的缺失而降低，这表明它们可能作为功能伙伴一起参与脂肪代谢。为了支持这一观点，LBP-5 易位到细胞核内，在那里它似乎影响参与能量代谢的秀丽隐杆线虫 NHR-49 靶基因。有趣的是，LBP-5 是硬脂酸诱导 NHR-49 靶基因转录所必需的。因此，这些知识可以帮助确定治疗肥胖症和与线虫宿主相互作用相关疾病的治疗靶点。
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