Astrocytes Control Food Intake by Inhibiting AGRP Neuron Activity via Adenosine A1 Receptors

• Astrocytic bidirectional regulation of ghrelin- and leptin-regulated feeding behaviors
• Endogenous adenosine mediates astrocytic inhibition of food intake
• Adenosine A1 receptors contribute to astrocytic inhibition of food intake
• Astrocytic inactivation of AGRP neurons via adenosine A1 receptors

SummaryIt is well recognized that feeding behavior in mammals is orchestrated by neurons within the medial basal hypothalamus. However, it remains unclear whether food intake is also under the control of glial cells. Here, we combine chemical genetics, cell-type-specific electrophysiology, pharmacology, and feeding assays to show that stimulation of astrocytes within the medial basal hypothalamus reduces both basal- and ghrelin-evoked food intake. This occurs by a mechanism of adenosine-mediated inactivation of the orexigenic agouti-related peptide (AGRP) neurons in the hypothalamic arcuate nucleus (ARC) via adenosine A1 receptors. Our data suggest that glial cells participate in regulating food intake by modulating extracellular levels of adenosine. These findings reveal the existence of a glial relay circuit that controls feeding behavior, one that might serve as a target for therapeutic intervention in the treatment of appetite disorders.

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