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mTORC1 in AGRP neurons integrates exteroceptive and interoceptive food-related cues in the modulation of adaptive energy expenditure in mice

Luke K Burke, Tamana Darwish, Althea R Cavanaugh, Sam Virtue, Emma Roth, Joanna Moro, Shun-Mei Liu, Jing Xia, Jeffrey W. Dalley, Keith Burling, Streamson Chua, Toni Vidal-Puig, Gary J Schwartz, Clémence Blouet
doi: https://doi.org/10.1101/110544
Luke K Burke
1MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 OQQ, UK
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Tamana Darwish
1MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 OQQ, UK
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Althea R Cavanaugh
2Departments of Medicine and Neuroscience, The Albert Einstein College of Medicine, New York 10461, USA
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Sam Virtue
1MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 OQQ, UK
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Emma Roth
1MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 OQQ, UK
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Joanna Moro
1MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 OQQ, UK
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Shun-Mei Liu
2Departments of Medicine and Neuroscience, The Albert Einstein College of Medicine, New York 10461, USA
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Jing Xia
3Department of Psychology, Behavioural and Clinical Neuroscience Institute University of Cambridge, Cambridge CB2 3EB, UK
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Jeffrey W. Dalley
3Department of Psychology, Behavioural and Clinical Neuroscience Institute University of Cambridge, Cambridge CB2 3EB, UK
4Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 2QQ, UK
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Keith Burling
1MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 OQQ, UK
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Streamson Chua
2Departments of Medicine and Neuroscience, The Albert Einstein College of Medicine, New York 10461, USA
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Toni Vidal-Puig
1MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 OQQ, UK
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Gary J Schwartz
2Departments of Medicine and Neuroscience, The Albert Einstein College of Medicine, New York 10461, USA
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Clémence Blouet
1MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 OQQ, UK
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Abstract

Energy dissipation through interscapular brown adipose tissue (iBAT) thermogenesis is an important contributor to adaptive energy expenditure. However, it remains unresolved how acute and chronic changes in energy availability are detected by the brain to adjust iBAT activity and maintain energy homeostasis. Here we provide evidence that AGRP inhibitory tone to iBAT represents an energy-sparing circuit that integrates environmental food cues and internal signals of energy availability. We establish a role for the nutrient-sensing mTORC1 signaling pathway within AGRP neurons in the detection of environmental food cues and internal signals of energy availability, and in the bi-directional control of iBAT thermogenesis during nutrient deficiency and excess. Collectively, our findings provide insights into how mTORC1 signaling within AGRP neurons surveys energy availability to engage iBAT thermogenesis, and identify AGRP neurons as a neuronal substrate for the coordination of energy intake and adaptive expenditure under varying physiological and environmental contexts.

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Posted February 22, 2017.
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mTORC1 in AGRP neurons integrates exteroceptive and interoceptive food-related cues in the modulation of adaptive energy expenditure in mice
Luke K Burke, Tamana Darwish, Althea R Cavanaugh, Sam Virtue, Emma Roth, Joanna Moro, Shun-Mei Liu, Jing Xia, Jeffrey W. Dalley, Keith Burling, Streamson Chua, Toni Vidal-Puig, Gary J Schwartz, Clémence Blouet
bioRxiv 110544; doi: https://doi.org/10.1101/110544
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mTORC1 in AGRP neurons integrates exteroceptive and interoceptive food-related cues in the modulation of adaptive energy expenditure in mice
Luke K Burke, Tamana Darwish, Althea R Cavanaugh, Sam Virtue, Emma Roth, Joanna Moro, Shun-Mei Liu, Jing Xia, Jeffrey W. Dalley, Keith Burling, Streamson Chua, Toni Vidal-Puig, Gary J Schwartz, Clémence Blouet
bioRxiv 110544; doi: https://doi.org/10.1101/110544

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