The incidence and prevalence of obesity and its associated comorbidities continue to rise, representing one of the major factors in the leading causes of death confronting modern society. Yet despite considerable efforts aimed at prevention and treatment, no safe and efficient anti-obesity drugs or interventions have had success in tackling this prevalence. Emerging evidence points out that the brain, in particular the hypothalamus, controls most aspects of systemic metabolism, suggesting that obesity may be a disease of the brain. Over the last decades, most studies have been restricted to exploring the functionality of neurons for understanding how the hypothalamus governs feeding behavior and systemic metabolism, ignoring the presence and potential function of other cell types in the brain, such as astrocytes. Increasing evidence highlights that astrocytes are key in the brain’s control of metabolism, positioning them as potential targets for improved pharmacological strategies to prevent and treat metabolic diseases. In summary, I propose to: (Aim 1) understand the ability of astrocytes to release gliotransmitters to neurons, (Aim 2) assess how astrocytes respond to neuronal activity, and (Aim 3) test if high-fat high-sugar diet (HFHS)- induced astrogliosis interrupts this crosstalk and contributes to the development of obesity and type 2 diabetes.