Drosophila insulin-like peptide-6 (dilp6) expression from fat body extends lifespan and represses secretion of Drosophila insulin-like peptide-2 from the brain.
Drosophila insulin-like peptide-6 (dilp6) expression from fat body extends lifespan and represses secretion of Drosophila insulin-like peptide-2 from the brain.
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DOI：
10.1111/acel.12000
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发表时间：
2012-12
期刊：
影响因子：
7.8
通讯作者：
Tatar M
中科院分区：
文献类型：
--
作者：
Bai H;Kang P;Tatar M
胰岛素/胰岛素样生长因子信号的减少延长了不同物种的寿命，包括黑腹果蝇，其基因组编码7个胰岛素样肽(Dilp1-7)。其中，当dFOXO在脂肪体中过度表达延长寿命时，大脑中表达的DILP2减少与长寿保证有关。在这里，我们证明了胰岛素调节的转录因子dFOXO正向调节成人脂肪体中的Dilp6mRNA。在成人脂肪体中过度表达Dilp6可延长寿命并增加与长寿相关的代谢表型。成人脂肪体DILP6的表达抑制了脑中DILP2和DILP5mRNA的表达，并抑制了DILP2分泌到血淋巴中。在脂肪体中表达dFOXO的长寿益处，以及脂肪体中dFOXO对脑Dilp表达的非自主性影响，都被脂肪体中的RNAi同时抑制Dilp6所阻断。因此，Dilp6似乎在dFOXO、脂肪组织和大脑内分泌功能之间架起了桥梁，以调节果蝇的寿命。
Reduced insulin/IGF signaling extends lifespan in diverse species, including Drosophila melanogaster where the genome encodes seven insulin-like peptides (dilp1-7). Of these, reduced dilp2 expressed in the brain has been associated with longevity assurance when over-expression of dfoxo in fat bodies extends lifespan. Here, we show that the insulin-regulated transcription factor dFOXO positively modulates dilp6 mRNA in adult fat body. Over-expression of dilp6 in adult fat body extends lifespan and increases longevity-associated metabolic phenotypes. Adult fat body dilp6 expression represses dilp2 and dilp5 mRNA in the brain, and the secretion of DILP2 into the hemolymph. The longevity benefit of expressing dfoxo in fat body, and the nonautonomous effect of fat body dfoxo upon brain dilp expression, is blocked by simultaneously repressing dilp6 by RNAi in fat body. dilp6 thus appears to bridge dFOXO, adipose tissue and brain endocrine function to regulate Drosophila longevity.
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DOI：
10.1073/pnas.0809144106
发表时间：
2009-01-27
影响因子：
11.1
作者：
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影响因子：
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发表时间：
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影响因子：
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作者：
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影响因子：
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作者：
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