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Hypothalamic astrocytes control systemic glucose metabolism and energy balance.
Cell Metab. 34, 1532-1547.e6 (2022)
The hypothalamus is key in the control of energy balance. However, strategies targeting hypothalamic neurons have failed to provide viable options to treat most metabolic diseases. Conversely, the role of astrocytes in systemic metabolic control has remained largely unexplored. Here, we show that obesity promotes anatomically restricted remodeling of hypothalamic astrocyte activity. In the paraventricular nucleus (PVN) of the hypothalamus, chemogenetic manipulation of astrocytes results in bidirectional control of neighboring neuron activity, autonomic outflow, glucose metabolism, and energy balance. This process recruits a mechanism involving the astrocytic control of ambient glutamate levels, which becomes defective in obesity. Positive or negative chemogenetic manipulation of PVN astrocyte Ca2+ signals, respectively, worsens or improves metabolic status of diet-induced obese mice. Collectively, these findings highlight a yet unappreciated role for astrocytes in the direct control of systemic metabolism and suggest potential targets for anti-obesity strategy.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Pvn ; Astrocyte ; Energy Homeostasis ; Glucose Metabolism ; Glutamate ; Obesity
ISSN (print) / ISBN
1550-4131
e-ISSN
1932-7420
Journal
Cell Metabolism
Quellenangaben
Volume: 34,
Issue: 10,
Pages: 1532-1547.e6
Publisher
Elsevier
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Obesity (IDO)