Synphilin-1 alters metabolic homeostasis in a novel Drosophila obesity model.
Synphilin-1 alters metabolic homeostasis in a novel Drosophila obesity model.
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Synphilin-1在一种新型的果蝇肥胖模型中改变了代谢稳态。
DOI：
10.1038/ijo.2012.111
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发表时间：
2012-12
影响因子：
4.9
通讯作者：
Smith, W. W.
中科院分区：
文献类型：
--
作者：
Liu, J.;Li, T.;Yang, D.;Ma, R.;Moran, T. H.;Smith, W. W.
肥胖症的发病机制仍不完全清楚。果蝇具有与人类相似的神经内分泌系统和消化系统，是研究能量平衡的理想系统。在这里，我们报道了一种新的肥胖果蝇模型，其中人类蛋白质synphilin-1（SP1）在神经元中的表达促进了正能量平衡。为了进一步了解SP1在能量平衡调控中的作用，利用上游激活序列UAS/GAL 4系统构建了转人SP1基因果蝇。我们通过评估SP1表达、脂肪脂质沉积、食物摄入和果蝇运动活动来表征人SP1转基因果蝇，以确定肥胖样表型发展中的主要行为变化及其后果。与非转基因对照组相比，神经元中SP1的过表达增加了果蝇的体重，但外周细胞中没有。SP1增加食物摄入，但不影响自发活动。SP1增加了三酰甘油的水平，脂肪体细胞和脂滴的大小，表明SP1增加了脂-脂配置。生存研究表明，SP1转基因果蝇对食物剥夺的抵抗力更强。SP1调节lipin基因的表达，可能参与SP1诱导的脂肪沉积和饥饿抗性。这些研究表明，SP1的表达影响能量稳态的方式，提高积极的能量平衡，并提供了一个有用的肥胖模型，为未来的发病机制和治疗研究。
The pathogenesis of obesity remains incompletely understood. Drosophila have conserved neuroendocrine and digestion systems with human and become an excellent system for studying energy homeostasis. Here, we reported a novel obesity Drosophila model, in which expression of human protein, synphilin-1 (SP1), in neurons fosters positive energy balance. To further understand the actions of SP1 in energy balance control, the upstream activation sequence UAS/GAL4 system was used to generate human SP1 transgenic Drosophila. We characterized a human SP1 transgenic Drosophila by assessing SP1 expression, fat lipid deposition, food intake and fly locomotor activity to determine the major behavioral changes and their consequences in the development of the obesity-like phenotype. Overexpression of SP1 in neurons, but not peripheral cells, increased the body weight of flies compared with that of non-transgenic controls. SP1 increased food intake but did not affect locomotor activity. SP1 increased the levels of triacylglycerol, and the size of fat body cells and lipid droplets, indicating that SP1 increased lipid-fat disposition. Survival studies showed that SP1 transgenic flies were more resistant to food deprivation. SP1 regulated lipin gene expression that may participate in SP1-induced fat deposition and starvation resistance. These studies demonstrate that SP1 expression affects energy homeostasis in ways that enhance positive energy balance and provide a useful obesity model for future pathogenesis and therapeutic studies.
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DOI：
10.1073/pnas.0702726104
发表时间：
2007-05-15
影响因子：
11.1
作者：
Ja, William W.;Carvalho, Gil B.;Benzer, Seymour
通讯作者：
Benzer, Seymour
影响因子：
16.2
作者：
Al-Anzi, Bader;Sapin, Viveca;Waters, Christopher;Zinn, Kai;Wyman, Robert J.;Benzer, Seymour
通讯作者：
Benzer, Seymour
双重功能脂肪蛋白和甘油代谢。
影响因子：
10.9
作者：
Harris, Thurl E.;Finck, Brian N.
通讯作者：
Finck, Brian N.
影响因子：
4.8
作者：
Lee, G;Tanaka, M;Mouradian, MM
通讯作者：
Mouradian, MM
影响因子：
48
作者：
Ni, Jian-Quan;Markstein, Michele;Perrimon, Norbert
通讯作者：
Perrimon, Norbert