Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes

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Abstract

Glial cells perform critical functions that alter the metabolism and activity of neurons, and there is increasing interest in their role in appetite and energy balance. Leptin, a key regulator of appetite and metabolism, has previously been reported to influence glial structural proteins and morphology. Here, we demonstrate that metabolic status and leptin also modify astrocyte-specific glutamate and glucose transporters, indicating that metabolic signals influence synaptic efficacy and glucose uptake and, ultimately, neuronal function. We found that basal and glucose-stimulated electrical activity of hypothalamic proopiomelanocortin (POMC) neurons in mice were altered in the offspring of mothers fed a high-fat diet. In adulthood, increased body weight and fasting also altered the expression of glucose and glutamate transporters. These results demonstrate that whole-organism metabolism alters hypothalamic glial cell activity and suggest that these cells play an important role in the pathology of obesity.

Authors

Esther Fuente-Martín, Cristina García-Cáceres, Miriam Granado, María L. de Ceballos, Miguel Ángel Sánchez-Garrido, Beatrix Sarman, Zhong-Wu Liu, Marcelo O. Dietrich, Manuel Tena-Sempere, Pilar Argente-Arizón, Francisca Díaz, Jesús Argente, Tamas L. Horvath, Julie A. Chowen