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Role of Astrocytes in Leptin Signaling

Journal of Molecular Neuroscience volume 56, pages 829–839 (2015)Cite this article

Abstract

To test the hypothesis that astrocytic leptin signaling induces an overall potentiation of the neuronal response to leptin, we generated a new line of astrocyte-specific leptin receptor knockout (ALKO-Δ1) mice in which no leptin receptor is expressed in astrocytes. Corresponding to cell-specific Cre recombinase expression in hypothalamic astrocytes but not neurons, this new strain of ALKO mice had attenuated pSTAT3 signaling in the arcuate nucleus of the hypothalamus 30 min after intracerebroventricular delivery of leptin. In response to high-fat diet for 2 months, the ALKO mice showed a greater increase of percent fat and blood leptin concentration. This coincided with a mild reactive gliosis in the hypothalamus. Overall, the absence of leptin receptors in astrocytes attenuated hypothalamic pSTAT3 signaling, induced a mild reactive morphology, and promoted the development of diet-induced obesity. We conclude that leptin signaling in astrocytes is essential for the homeostasis of neuroendocrine regulation in obesity.

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Acknowledgments

Grant support was provided by NIH (DK54880, DK92245, NS62291). Cryosectioning was performed in the Cell Biology and Cell Imaging Core Facility with service charge.

Conflict of Interest

All authors have nothing to declare.

Author information

Affiliations

  1. Blood-Brain Barrier Group, Pennington Biomedical Research Center, Baton Rouge, LA, 70808, USA

    Yuping Wang, Hung Hsuchou, Yi He, Abba J. Kastin & Weihong Pan

  2. Biopotentials Sleep Center, 8032 Summa Ave, Ste A, Baton Rouge, LA, 70809, USA

    Weihong Pan

Authors
  1. Yuping Wang
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  2. Hung Hsuchou
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  3. Yi He
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  4. Abba J. Kastin
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  5. Weihong Pan
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Corresponding author

Correspondence to Weihong Pan.

Additional information

Wang and Hsuchou made equal contributions and are co-first authors.

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Wang, Y., Hsuchou, H., He, Y. et al. Role of Astrocytes in Leptin Signaling. J Mol Neurosci 56, 829–839 (2015). https://doi.org/10.1007/s12031-015-0518-5

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  • DOI: https://doi.org/10.1007/s12031-015-0518-5

Keywords

  • Leptin
  • Astrocyte
  • STAT3
  • Reactive astrogliosis
  • Obesity