RT Journal Article
SR Electronic
T1 mTORC1 in AGRP neurons integrates exteroceptive and interoceptive food-related cues in the modulation of adaptive energy expenditure in mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 110544
DO 10.1101/110544
A1 Luke K Burke
A1 Tamana Darwish
A1 Althea R Cavanaugh
A1 Sam Virtue
A1 Emma Roth
A1 Joanna Moro
A1 Shun-Mei Liu
A1 Jing Xia
A1 Jeffrey W. Dalley
A1 Keith Burling
A1 Streamson Chua
A1 Toni Vidal-Puig
A1 Gary J Schwartz
A1 Clémence Blouet
YR 2017
UL http://biorxiv.org/content/early/2017/02/21/110544.abstract
AB 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.