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Altered Metabolism and Persistent Starvation Behaviors Caused by Reduced AMPK Function in Drosophila

Johnson, Erik C.

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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 (AMPKγ) and through expression of a dominant negative alpha (AMPKα) 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 intake was greater in animals with reduced AMPK function yet total triglyceride levels were lower. AMPK mutant animals displayed starvation-like lipid accumulation patterns in metabolically key liver-like cells, oenocytes, even under fed conditions, consistent with a persistent starved state. Measurements of O2 consumption reveal that metabolic rates are greater in animals with reduced AMPK function. Lastly, rapamycin treatment tempers the starvation sensitivity and lethality associated with reduced AMPK function. Collectively, these results are consistent with models that AMPK shifts energy usage away from expenditures into a conservation mode during nutrient-limited conditions at a cellular level. The highly conserved AMPK subunits throughout the Metazoa, suggest such findings may provide significant insight for pharmaceutical strategies to manipulate AMPK function in humans.
This work was funded by the Science Research Fund of Wake Forest University and National Science Foundation (NSF) Integrative Organismal Systems (IOS) grant 092931 to ECJ and National Institutes of Health (NIH) grant MH073155 to JEB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. (sponsorship)
diabetes and endocrinology
genetics and genomics
9 (issue)
5 (volume)
Johnson, Erik C. (author)
Kazgan, Nevzat (author)
Bretz, Colin A. (author)
Forsberg, Lawrence J. (author)
Hector, Clare E. (author)
Worthen, Ryan J. (author)
Onyenwoke, Rob (author)
Brenman, Jay E. (author)
2012-08-07T20:14:33Z (accessioned)
2012-08-07T20:14:33Z (available)
2010-09 (issued)
Johnson EC, Kazgan N, Bretz CA, Forsberg LJ, Hector CE, et al. (2010) Altered Metabolism and Persistent Starvation Behaviors Caused by Reduced AMPK Function in Drosophila. PLoS ONE 5(9): e12799. doi:10.1371/journal.pone.0012799 (citation)
http://hdl.handle.net/10339/37397 (uri)
http://dx.doi.org/10.1371/journal.pone.0012799 (uri)
PLoS: Public Library of Science
Altered Metabolism and Persistent Starvation Behaviors Caused by Reduced AMPK Function in Drosophila

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