Hypothalamic astrocytes control systemic glucose metabolism and energy balance
Cell Metabolism. 2022-10-01; 34(10): 1532-1547.e6
DOI: 10.1016/j.cmet.2022.09.002
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https://www.bordeaux-neurocampus.fr/12614
1. Cell Metab. 2022 Oct 4;34(10):1532-1547.e6. doi: 10.1016/j.cmet.2022.09.002.
Hypothalamic astrocytes control systemic glucose metabolism and energy balance.
Herrera Moro Chao D(1), Kirchner MK(2), Pham C(3), Foppen E(4), Denis RGP(5),
Castel J(4), Morel C(4), Montalban E(4), Hassouna R(4), Bui LC(4), Renault J(4),
Mouffle C(3), García-Cáceres C(6), Tschöp MH(7), Li D(3), Martin C(4), Stern
JE(2), Luquet SH(8).
Author information:
(1)Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative,
Paris, France. Electronic address: .
(2)Neuroscience Institute, Georgia State University, Atlanta, GA 30303, USA;
Center for Neuroinflammation and Cardiometabolic Diseases, Georgia State
University, Atlanta, GA 30302, USA.
(3)Institute of Biology Paris Seine, Neuroscience Paris Seine, CNRS UMR8246,
INSERM U1130, Sorbonne Universite, Paris 75005, France.
(4)Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative,
Paris, France.
(5)Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative,
Paris, France; Institut Cochin, Université Paris Cité, INSERM U1016, CNRS UMR
8104, 75014 Paris, France.
(6)Helmholtz Diabetes Center (HDC) & German Center for Diabetes Research
(DZD), Helmholtz Zentrum München, Neuherberg, 85764, Germany; Division of
Metabolic Diseases, Technische Universität München, Munich, 80333, Germany;
Medizinische Klinik and Poliklinik IV, Klinikum der Universität,
Ludwig-Maximilians-Universität München, Munich, Germany.
(7)Helmholtz Diabetes Center (HDC) & German Center for Diabetes Research
(DZD), Helmholtz Zentrum München, Neuherberg, 85764, Germany; Division of
Metabolic Diseases, Technische Universität München, Munich, 80333, Germany.
(8)Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative,
Paris, France. Electronic address: .
Comment in
Cell Metab. 2022 Oct 4;34(10):1424-1426. doi: 10.1016/j.cmet.2022.09.012.
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.
Copyright © 2022 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.cmet.2022.09.002
PMCID: PMC9615252
PMID: 36198294 [Indexed for MEDLINE]
Conflict of interest statement: Declaration of interests The authors declare no
competing interests.