Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes

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 obesityThis work was supported by grants from the Spanish Government (FIS PI100747, BFU2011-27492, and CIBER de Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain). E. Fuente-Martín is supported by a postdoctoral fellowship from CIBERobn. T.L. Horvath was supported by NIH grants DK080000 and DK006850 and an ADA Fellowship gran