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Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes
Esther Fuente-Martín, … , Tamas L. Horvath, Julie A. Chowen
Esther Fuente-Martín, … , Tamas L. Horvath, Julie A. Chowen
Published October 15, 2012
Citation Information: J Clin Invest. 2012;122(11):3900-3913. https://doi.org/10.1172/JCI64102.
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Research Article Metabolism

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

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Figure 1

Modification of hypothalamic astrocytes in response to NeoON.

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Modification of hypothalamic astrocytes in response to NeoON.
(A) GFAP l...
(A) GFAP levels in the hypothalamus of rats from litters of 12 pups (control [Ct]) and litters of 4 pups with NeoON. (B) Photomicrographs of immunohistochemistry for GFAP in the arcuate nucleus of (B) control and (C) NeoON rats. Morphological analysis demonstrated that in NeoON adults, there was an increase in the number of GFAP+ cells in the arcuate nucleus (D) and the number of primary projections/GFAP+ cell (E), with no difference in the mean projection length (F). *P < 0.05; **P < 0.01; ***P < 0.001. Scale bars: 50 μm.
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