Department of Neuroscience, The University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
PLoS One. 2011;6(5):e19921. doi: 10.1371/journal.pone.0019921. Epub 2011 May 18.
A proper balance of lipid breakdown and synthesis is essential for achieving energy homeostasis as alterations in either of these processes can lead to pathological states such as obesity. The regulation of lipid metabolism is quite complex with multiple signals integrated to control overall triglyceride levels in metabolic tissues. Based upon studies demonstrating effects of the circadian clock on metabolism, we sought to determine if the central clock cells in the Drosophila brain contribute to lipid levels in the fat body, the main nutrient storage organ of the fly. Here, we show that altering the function of the Drosophila central clock neurons leads to an increase in fat body triglycerides. We also show that although triglyceride levels are not affected by age, they are increased by expression of the amyloid-beta protein in central clock neurons. The effect on lipid storage seems to be independent of circadian clock output as changes in triglycerides are not always observed in genetic manipulations that result in altered locomotor rhythms. These data demonstrate that the activity of the central clock neurons is necessary for proper lipid storage.
脂质的分解和合成之间保持适当的平衡对于实现能量平衡至关重要,因为这两个过程中的任何一个的改变都可能导致肥胖等病理状态。脂质代谢的调节非常复杂,需要整合多种信号来控制代谢组织中的总体甘油三酯水平。基于表明生物钟对代谢有影响的研究,我们试图确定果蝇大脑中的中枢生物钟细胞是否有助于脂肪体中的脂质水平,脂肪体是果蝇的主要营养储存器官。在这里,我们表明改变果蝇中枢生物钟神经元的功能会导致脂肪体甘油三酯含量增加。我们还表明,尽管甘油三酯水平不受年龄影响,但在中枢生物钟神经元中表达淀粉样β蛋白会使其增加。这种对脂质储存的影响似乎与生物钟输出无关,因为在导致运动节律改变的遗传操作中,并非总是观察到甘油三酯的变化。这些数据表明,中枢生物钟神经元的活性对于适当的脂质储存是必要的。