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

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Burke, LK 
Darwish, T 
Cavanaugh, AR 
Virtue, S 
Roth, E 


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.



brown fat, energy expenditure, human biology, hypothalamus, mTORC1, medicine, mouse, neuroscience, nutrient-sensing, obesity, Adipose Tissue, Agouti-Related Protein, Animals, Energy Metabolism, Mechanistic Target of Rapamycin Complex 1, Mice, Neurons, Signal Transduction, Thermogenesis

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eLife Sciences Publications Ltd
Wellcome Trust (100574/Z/12/Z)
Medical Research Council (MC_UU_12012/1)
Medical Research Council (MR/N003276/1)
Medical Research Council (MC_UU_12012/2)
Medical Research Council (MC_UU_12012/5)
Biotechnology and Biological Sciences Research Council (BB/J009865/1)
Medical Research Council (G0802051)
MRC (MR/M501736/1)
Medical Research Council (MC_PC_12012)
This work was supported by the Medical Research Council New Blood Fellowship [MR/M501736/1] to CB, a NIDDK K99/R00 award to CB, the Medical Research Council Metabolic Disease Unit programme grant, the Disease Model Core facilities, and the Wellcome Trust Cambridge Mouse Biochemistry Laboratory. Animal procedures were performed under Tony Coll’s home office PPL 80/2497 and Toni Vidal-Puig PPL 80/2484.
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