Dorsal vagal complex and hypothalamic glia differentially respond to leptin and energy balance dysregulation

Lauren M. Stein, Rinzin Lhamo, Anh Cao, Jayme Workinger, Ian Tinsley, Robert P. Doyle, Harvey J. Grill, Gerlinda E. Hermann, Richard C. Rogers, Matthew R. Hayes

Research output: Contribution to journalArticle

Abstract

Previous studies identify a role for hypothalamic glia in energy balance regulation; however, a narrow hypothalamic focus provides an incomplete understanding of how glia throughout the brain respond to and regulate energy homeostasis. We examined the responses of glia in the dorsal vagal complex (DVC) to the adipokine leptin and high fat diet-induced obesity. DVC astrocytes functionally express the leptin receptor; in vivo pharmacological studies suggest that DVC astrocytes partly mediate the anorectic effects of leptin in lean but not diet-induced obese rats. Ex vivo calcium imaging indicated that these changes were related to a lower proportion of leptin-responsive cells in the DVC of obese versus lean animals. Finally, we investigated DVC microglia and astroglia responses to leptin and energy balance dysregulation in vivo: obesity decreased DVC astrogliosis, whereas the absence of leptin signaling in Zucker rats was associated with extensive astrogliosis in the DVC and decreased hypothalamic micro- and astrogliosis. These data uncover a novel functional heterogeneity of astrocytes in different brain nuclei of relevance to leptin signaling and energy balance regulation.

Original languageEnglish (US)
Article number90
JournalTranslational Psychiatry
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

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    Stein, L. M., Lhamo, R., Cao, A., Workinger, J., Tinsley, I., Doyle, R. P., Grill, H. J., Hermann, G. E., Rogers, R. C., & Hayes, M. R. (2020). Dorsal vagal complex and hypothalamic glia differentially respond to leptin and energy balance dysregulation. Translational Psychiatry, 10(1), [90]. https://doi.org/10.1038/s41398-020-0767-0