原创力文档regulation of energy stores and feeding by neuronal and peripheral creb activity in drosophila监管的能量存储和喂养果蝇的神经和周围分子活动.pdfVIP
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regulation of energy stores and feeding by neuronal and peripheral creb activity in drosophila监管的能量存储和喂养果蝇的神经和周围分子活动
Regulation of Energy Stores and Feeding by Neuronal
and Peripheral CREB Activity in Drosophila
1 1 2 2
Koichi Iijima *, LiJuan Zhao , Christopher Shenton , Kanae Iijima-Ando *
1 Laboratory of Neurodegenerative and Metabolic Diseases, Farber Institute for Neurosciences, Department of Biochemistry and Molecular Biology, Thomas Jefferson
University, Philadelphia, Pennsylvania, United States of America, 2 Laboratory of Neurogenetics and Pathobiology, Farber Institute for Neurosciences, Department of
Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America
Abstract
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.
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