Regulation of energy stores and feeding by neuronal and peripheral CREB activity in Drosophila.
Regulation of energy stores and feeding by neuronal and peripheral CREB activity in Drosophila.
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DOI：
10.1371/journal.pone.0008498
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发表时间：
2009-12-30
期刊：
影响因子：
3.7
通讯作者：
Iijima-Ando K
中科院分区：
文献类型：
--
作者：
Iijima K;Zhao L;Shenton C;Iijima-Ando K
camp应答转录因子CREB在哺乳动物脂肪组织和肝脏中起调节糖原和脂质代谢的作用。虽然果蝇具有哺乳动物CREB的同源物dCREB2，但其在能量代谢中的作用尚不完全清楚。利用CREB显性阴性形式的组织特异性表达（DN-CREB），我们研究了阻断神经元和脂肪体（具有脂肪组织和肝脏功能的主要能量储存库）中CREB活性对能量平衡、应激抵抗和摄食行为的影响。我们发现神经元中CREB功能的破坏减少了糖原和脂质储存，增加了对饥饿的敏感性。DN-CREB在脂肪体中的表达也降低了糖原水平，但它不影响饥饿敏感性，可能是由于这些果蝇的脂质水平增加。有趣的是，在脂肪体中阻断CREB活动会增加食物摄入量。这些果蝇在整体体型上没有表现出显著的变化，这表明脂肪体中CREB活动的破坏导致了肥胖样表型。利用转基因cre -荧光素酶报告基因，我们进一步证明，在果蝇中，脂肪体中与哺乳动物胰高血糖素和β-肾上腺素能信号相关的脂肪动力学激素受体的破坏会减少cre介导的转录。本研究表明，无论是在神经元还是外周组织中，CREB的活性都能调节果蝇的能量平衡，并且外周组织中调节CREB活性的关键信号通路具有进化保守性。
The cAMP-responsive transcription factor CREB functions in adipose tissue and liver to regulate glycogen and lipid metabolism in mammals. While Drosophila has a homolog of mammalian CREB, dCREB2, its role in energy metabolism is not fully understood. Using tissue-specific expression of a dominant-negative form of CREB (DN-CREB), we have examined the effect of blocking CREB activity in neurons and in the fat body, the primary energy storage depot with functions of adipose tissue and the liver in flies, on energy balance, stress resistance and feeding behavior. We found that disruption of CREB function in neurons reduced glycogen and lipid stores and increased sensitivity to starvation. Expression of DN-CREB in the fat body also reduced glycogen levels, while it did not affect starvation sensitivity, presumably due to increased lipid levels in these flies. Interestingly, blocking CREB activity in the fat body increased food intake. These flies did not show a significant change in overall body size, suggesting that disruption of CREB activity in the fat body caused an obese-like phenotype. Using a transgenic CRE-luciferase reporter, we further demonstrated that disruption of the adipokinetic hormone receptor, which is functionally related to mammalian glucagon and β-adrenergic signaling, in the fat body reduced CRE-mediated transcription in flies. This study demonstrates that CREB activity in either neuronal or peripheral tissues regulates energy balance in Drosophila, and that the key signaling pathway regulating CREB activity in peripheral tissue is evolutionarily conserved.
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影响因子：
10.5
作者：
Dauwalder, B;Tsujimoto, S;Mattox, W
通讯作者：
Mattox, W
影响因子：
9.8
作者：
Grönke S;Müller G;Hirsch J;Fellert S;Andreou A;Haase T;Jäckle H;Kühnlein RP
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Kühnlein RP
影响因子：
64.8
作者：
Herzig, S;Hedrick, S;Montminy, M
通讯作者：
Montminy, M
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
DOI：
10.1073/pnas.1932773100
发表时间：
2003-10-14
影响因子：
11.1
作者：
Iourgenko, V;Zhang, WJ;Labow, MA
通讯作者：
Labow, MA