mTORC1 in AGRP neurons integrates exteroceptive and interoceptive food-related cues in the modulation of adaptive energy expenditure in mice
| Autor: | Streamson C. Chua, Tamana Darwish, Keith Burling, Toni Vidal-Puig, Joanna Morro, Luke K. Burke, Sam Virtue, Clemence Blouet, Gary J. Schwartz, Althea R. Cavanaugh, Jing Xia, Shun Mei Liu, Emma Roth, Jeffrey W. Dalley |
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| Přispěvatelé: | Dalley, Jeffrey [0000-0002-2282-3660], Blouet, Clemence [0000-0002-1752-1270], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
obesity mTORC1 Energy homeostasis neuroscience Mice 0302 clinical medicine Brown adipose tissue energy expenditure Agouti-Related Protein hypothalamus Biology (General) Neurons 2. Zero hunger 0303 health sciences nutrient-sensing General Neuroscience digestive oral and skin physiology human biology brown fat Thermogenesis General Medicine medicine.anatomical_structure Mtorc1 signaling Adipose Tissue Energy expenditure Hypothalamus Medicine Research Article Signal Transduction medicine.medical_specialty QH301-705.5 Science Nutrient sensing Mechanistic Target of Rapamycin Complex 1 Biology Inhibitory postsynaptic potential General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Internal medicine medicine Animals Human Biology and Medicine mouse 030304 developmental biology General Immunology and Microbiology 030104 developmental biology Endocrinology nervous system Nutrient deficiency Energy Metabolism Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | eLife, Vol 6 (2017) eLife |
| Popis: | 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. DOI: http://dx.doi.org/10.7554/eLife.22848.001 eLife digest Losing weight through dieting can be difficult. Weight loss strategies often prove ineffective because the body works like a thermostat and couples what we eat to the number of calories we burn. When we eat less, our bodies compensate and burn fewer calories, which makes losing weight harder. The brain is the master regulator of this caloric thermostat, but it is not clear how it adjusts our energy expenditure to account for how much we have eaten. A structure deep within the brain called the hypothalamus, which helps regulate appetite, is thought to be involved in the caloric thermostat. Activating a group of neurons within the hypothalamus called the agouti-related neuropeptide (AGRP) neurons causes animals to consume large quantities of food. By contrast, inhibiting AGRP neurons causes animals to stop eating almost entirely. Burke et al. studied AGRP neurons in mice. The experiments show that artificially activating the neurons in mice that don’t have access to food increases the animals’ activity levels but reduces the rate at which they burn calories, which helps the mice to maintain their existing weight. Allowing the mice to eat, or even just to see and smell food, switches off this effect and returns energy expenditure to normal. Finally, exposing mice to a high-fat diet for several days inhibits their AGRP neurons, and causes the animals to burn calories at a faster rate. By using up excess calories, this change also helps the animals maintain their existing body weight. The findings of Burke et al. show that AGRP neurons are a key component of the caloric thermostat. By adjusting the rate at which the body burns calories, AGRP neurons can compensate for any changes in food intake and so limit changes in body weight. This work opens up the possibility of developing therapies that disconnect energy expenditure from energy intake to help maintain long-term weight loss. DOI: http://dx.doi.org/10.7554/eLife.22848.002 |
| Databáze: | OpenAIRE |
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