Astrocyte involvement in metabolic regulation and disease

HighlightsAstrocytes in different brain regions are highly heterogeneous in morphology and function, and contribute to diverse brain functions.Astrocytes respond to metabolic, hormonal, and environmental stimuli relevant to diabetes and obesity to regulate neurovascular coupling, synaptic plasticity, neurotransmitter regulation, immune response, and neuronal energy metabolism.Dysregulation of astrocytic glucose sensing affects thermoregulation, insulin sensitivity, and the overall energy balance of the body.The sex-specific role of astrocytes and their response to hormonal fluctuations provide insights into sex differences in metabolic regulation.Manipulation of astrocyte function may help to restore metabolic function.Innovative approaches to target astrocytes by gene delivery, optogenetics, chemogenetics, transplantation, and exosomes may unlock new treatments for diabetes and obesity.AbstractAstrocytes, the predominant glial cell type in the mammalian brain, influence a wide variety of brain parameters including neuronal energy metabolism. Exciting recent studies have shown that obesity and diabetes can impact on astrocyte function. We review evidence that dysregulation of astrocytic lipid metabolism and glucose sensing contributes to dysregulation of whole-body energy balance, thermoregulation, and insulin sensitivity. In addition, we consider the overlooked topic of the sex-specific roles of astrocytes and their response to hormonal fluctuations that provide insights into sex differences in metabolic regulation. Finally, we provide an update on potential ways to manipulate astrocyte function, including genetic targeting, optogenetic and chemogenetic techniques, transplantation, and tailored exosome-based therapies, which may lead to improved treatments for metabolic disease.