Hypothalamic Astrocytes as a Specialized and Responsive Cell Population in Obesity

Astrocytes are a type of glial cell anatomically and functionally integrated into the neuronal regulatory circuits for the neuroendocrine control of metabolism. Being functional integral compounds of synapses, astrocytes are actively involved in the physiological regulatory aspects of metabolic control, but also in the pathological processes that link neuronal dysfunction and obesity. Between brain areas, the hypothalamus harbors specialized functional circuits that seem selectively vulnerable to metabolic damage, undergoing early cellular rearrangements which are thought to be at the core of the pathogenesis of diet-induced obesity. Such changes in the hypothalamic brain region consist of a rise in proinflammatory cytokines, the presence of a reactive phenotype in astrocytes and microglia, alterations in the cytoarchitecture and synaptology of hypothalamic circuits, and angiogenesis, a phenomenon that cannot be found elsewhere in the brain. Increasing evidence points to the direct involvement of hypothalamic astrocytes in such early metabolic disturbances, thus moving the study of these glial cells to the forefront of obesity research. Here we provide a comprehensive review of the most relevant findings of molecular and pathophysiological mechanisms by which hypothalamic astrocytes might be involved in the pathogenesis of obesity.