期刊
CELL REPORTS
卷 36, 期 7, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2021.109563
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类别
资金
- Koopmans Research Award
- Canadian Institutes of Health Research [FDN-147473]
- Canada Research Chair Tier 1 [950-232211]
- Cumming School of Medicine
- Alberta Innovates Health Solutions
The overconsumption of highly palatable, energy-dense food is considered a key driver of the obesity pandemic. This study reveals that obesity disrupts astrocytes in the OFC, leading to a decrease in inhibitory GABA transmission between neurons.
Overconsumption of highly palatable, energy-dense food is considered a key driver of the obesity pandemic. The orbitofrontal cortex (OFC) is critical for reward valuation of gustatory signals, yet how the OFC adapts to obesogenic diets is poorly understood. Here, we show that extended access to a cafeteria diet impairs astrocyte glutamate clearance, which leads to a heterosynaptic depression of GABA transmission onto pyramidal neurons of the OFC. This decrease in GABA tone is due to an increase in extrasynaptic glutamate, which acts via metabotropic glutamate receptors to liberate endocannabinoids. This impairs the induction of endocannabinoid-mediated long-term plasticity. The nutritional supplement, N-acetylcysteine rescues this cascade of synaptic impairments by restoring astrocytic glutamate transport. Together, our findings indicate that obesity targets astrocytes to disrupt the delicate balance between excitatory and inhibitory transmission in the OFC.
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