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
Affiliations
Luke K Burke
MRC Metabolic Diseases Unit, Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom; WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom
Tamana Darwish
MRC Metabolic Diseases Unit, Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom; WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom
Althea R Cavanaugh
Departments of Medicine and Neuroscience, The Albert Einstein College of Medicine, New York, United States
Sam Virtue
MRC Metabolic Diseases Unit, Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom; WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom
MRC Metabolic Diseases Unit, Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom; WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom
Joanna Morro
MRC Metabolic Diseases Unit, Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom; WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom
Shun-Mei Liu
Departments of Medicine and Neuroscience, The Albert Einstein College of Medicine, New York, United States
Jing Xia
Department of Psychology, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom
Jeffrey W Dalley
Department of Psychology, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom; Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom
Keith Burling
MRC Metabolic Diseases Unit, Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom; WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom
Streamson Chua
Departments of Medicine and Neuroscience, The Albert Einstein College of Medicine, New York, United States
Toni Vidal-Puig
MRC Metabolic Diseases Unit, Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom; WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom
Gary J Schwartz
Departments of Medicine and Neuroscience, The Albert Einstein College of Medicine, New York, United States
MRC Metabolic Diseases Unit, Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom; WT-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom
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.
