Hypothalamic astrocytes control systemic glucose metabolism and energy balance

Daniela Herrera Moro Chao, Matthew K. Kirchner, Cuong Pham, Ewout Foppen, Raphael G. P. Denis, Julien Castel, Chloe Morel, Enrica Montalban, Rim Hassouna, Linh-Chi Bui, Justine Renault, Christine Mouffle, Cristina García-Cáceres, Matthias H. Tschöp, Dongdong Li, Claire Martin, Javier E. Stern, Serge H. Luquet

Research output: Contribution to journalArticleAcademicpeer-review

28 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1532-1547.e6
JournalCell metabolism
Volume34
Issue number10
DOIs
Publication statusPublished - 4 Oct 2022

Keywords

  • PVN
  • astrocyte
  • energy homeostasis
  • glucose metabolism
  • glutamate
  • obesity

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