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 Morro, Shun Mei Liu, Jing Xia, Jeffrey W. Dalley, Keith Burling, Streamson Chua, Toni Vidal-Puig, Gary J. Schwartz, Clémence Blouet

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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.

Original languageEnglish (US)
Article numbere22848
JournaleLife
Volume6
DOIs
StatePublished - May 23 2017

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Burke, L. K., Darwish, T., Cavanaugh, A. R., Virtue, S., Roth, E., Morro, J., Liu, S. M., Xia, J., Dalley, J. W., Burling, K., Chua, S., Vidal-Puig, T., Schwartz, G. J., & Blouet, C. (2017). mTORC1 in AGRP neurons integrates exteroceptive and interoceptive food-related cues in the modulation of adaptive energy expenditure in mice. eLife, 6, [e22848]. https://doi.org/10.7554/eLife.22848