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Herrera Moro Chao, D.* ; Kirchner, M.K.* ; Pham, C.* ; Foppen, E.* ; Denis, R.G.P.* ; Castel, J.* ; Morel, C.* ; Montalban, E.* ; Hassouna, R.* ; Bui, L.C.* ; Renault, J.* ; Mouffle, C.* ; García-Cáceres, C. ; Tschöp, M.H. ; Li, D.* ; Martin, C.* ; Stern, J.E.* ; Luquet, S.H.*

Hypothalamic astrocytes control systemic glucose metabolism and energy balance.

Cell Metab. 34, 1532-1547.e6 (2022)
Verlagsversion Postprint DOI PMC
Open Access Green
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Pvn ; Astrocyte ; Energy Homeostasis ; Glucose Metabolism ; Glutamate ; Obesity
ISSN (print) / ISBN 1550-4131
e-ISSN 1932-7420
Zeitschrift Cell Metabolism
Quellenangaben Band: 34, Heft: 10, Seiten: 1532-1547.e6 Artikelnummer: , Supplement: ,
Verlag Elsevier
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)