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A fat-tissue sensor couples growth to oxygen availability by remotely controlling insulin secretion

View ORCID ProfileMichael J. Texada, Anne F. Joergensen, Christian F. Christensen, Daniel K. Smith, Dylan F.M. Marple, E. Thomas Danielsen, Sine K. Petersen, Jakob L. Hansen, Kenneth A. Halberg, Kim F. Rewitz
doi: https://doi.org/10.1101/348334
Michael J. Texada
1Department of Biology, University of Copenhagen, Copenhagen, Denmark
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  • ORCID record for Michael J. Texada
Anne F. Joergensen
1Department of Biology, University of Copenhagen, Copenhagen, Denmark
2Cardiovascular Research, Department number 5377, Novo Nordisk A/S, Novo Nordisk Park 1, 2760 Måløv, Denmark
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Christian F. Christensen
1Department of Biology, University of Copenhagen, Copenhagen, Denmark
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Daniel K. Smith
1Department of Biology, University of Copenhagen, Copenhagen, Denmark
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Dylan F.M. Marple
1Department of Biology, University of Copenhagen, Copenhagen, Denmark
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E. Thomas Danielsen
1Department of Biology, University of Copenhagen, Copenhagen, Denmark
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Sine K. Petersen
1Department of Biology, University of Copenhagen, Copenhagen, Denmark
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Jakob L. Hansen
2Cardiovascular Research, Department number 5377, Novo Nordisk A/S, Novo Nordisk Park 1, 2760 Måløv, Denmark
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Kenneth A. Halberg
1Department of Biology, University of Copenhagen, Copenhagen, Denmark
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Kim F. Rewitz
1Department of Biology, University of Copenhagen, Copenhagen, Denmark
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  • For correspondence: Kim.Rewitz@bio.ku.dk
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Abstract

Organisms adapt their metabolism and growth to the availability of nutrients and oxygen, which are essential for normal development. This requires the ability to sense these environmental factors and respond by regulation of growth-controlling signals, yet the mechanisms by which this adaptation occurs are not fully understood. To identify novel growth-regulatory mechanisms, we conducted a global RNAi-based screen in Drosophila for size differences and identified 89 positive and negative regulators of growth. Among the strongest hits was the FGFR homologue breathless necessary for proper development of the tracheal airway system. Breathless deficiency results in tissue hypoxia (low oxygen), sensed primarily in this context by the fat tissue. The fat, in response, relays this information through release of one or more humoral factors that remotely inhibit insulin secretion from the brain, thereby restricting systemic growth. Thus our findings show that the fat tissue acts as an oxygen sensor that allows the organism to reduce its growth in adaptation to limited oxygen conditions.

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Posted June 15, 2018.
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A fat-tissue sensor couples growth to oxygen availability by remotely controlling insulin secretion
Michael J. Texada, Anne F. Joergensen, Christian F. Christensen, Daniel K. Smith, Dylan F.M. Marple, E. Thomas Danielsen, Sine K. Petersen, Jakob L. Hansen, Kenneth A. Halberg, Kim F. Rewitz
bioRxiv 348334; doi: https://doi.org/10.1101/348334
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A fat-tissue sensor couples growth to oxygen availability by remotely controlling insulin secretion
Michael J. Texada, Anne F. Joergensen, Christian F. Christensen, Daniel K. Smith, Dylan F.M. Marple, E. Thomas Danielsen, Sine K. Petersen, Jakob L. Hansen, Kenneth A. Halberg, Kim F. Rewitz
bioRxiv 348334; doi: https://doi.org/10.1101/348334

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