altered metabolism and persistent starvation behaviors caused by reduced ampk function in drosophila改变新陈代谢和持续的饥饿行为引起的减少ampk函数在果蝇.pdfVIP

Altered Metabolism and Persistent Starvation Behaviors Caused by Reduced AMPK Function in Drosophila 1,2 3 1 3 1 Erik C. Johnson *, Nevzat Kazgan , Colin A. Bretz , Lawrence J. Forsberg , Clare E. Hector , Ryan J. 3 3 3,4 Worthen , Rob Onyenwoke , Jay E. Brenman * 1 Department of Biology, Wake Forest University, Winston-Salem, North Carolina, United States of America, 2 Translational Science Center, Wake Forest University, Winston-Salem, North Carolina, United States of America, 3 Neuroscience Center, University of North Carolina, Chapel Hill, North Carolina, United States of America, 4 Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina, United States of America Abstract Organisms must utilize multiple mechanisms to maintain energetic homeostasis in the face of limited nutrient availability. One mechanism involves activation of the heterotrimeric AMP-activated protein kinase (AMPK), a cell-autonomous sensor to energetic changes regulated by ATP to AMP ratios. We examined the phenotypic consequences of reduced AMPK function, both through RNAi knockdown of the gamma subunit (AMPKc) and through expression of a dominant negative alpha (AMPKa) variant in Drosophila melanogaster. Reduced AMPK signaling leads to hypersensitivity to starvation conditions as measured by lifespan and locomotor activity. Locomotor levels in flies with reduced AMPK function were lower during unstressed conditions, but starvation-induced hyperactivity, an adaptive response to encourage foraging, was significantly higher than in wild type. Unexpectedly, total dietary