Brainstem astrocytes control homeostatic regulation of caloric intake

Courtney Clyburn, Kaitlin E. Carson, Caleb R. Smith, R. Alberto Travagli, Kirsteen N. Browning

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Abstract: Prolonged high-fat diet (HFD) exposure is associated with hyperphagia, excess caloric intake and weight gain. After initial exposure to a HFD, a brief (24–48 h) period of hyperphagia is followed by the regulation of caloric intake and restoration of energy balance within an acute (3–5 day) period. Previous studies have demonstrated this occurs via a vagally mediated signalling cascade that increases glutamatergic transmission via activation of NMDA receptors located on gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). The present study used electrophysiological recordings from thin brainstem slice preparations, in vivo recordings of gastric motility and tone, measurement of gastric emptying rates, and food intake studies to investigate the hypothesis that activation of brainstem astrocytes in response to acute HFD exposure is responsible for the increased glutamatergic drive to DMV neurons and the restoration of caloric balance. Pharmacological and chemogenetic inhibition of brainstem astrocytes reduced glutamatergic signalling and DMV excitability, dysregulated gastric tone and motility, attenuated the homeostatic delay in gastric emptying, and prevented the decrease in food intake that is observed during the period of energy regulation following initial exposure to HFD. Understanding the mechanisms involved in caloric regulation may provide critical insights into energy balance as well as into the hyperphagia that develops as these mechanisms are overcome. (Figure presented.). Key points: Initial exposure to a high fat diet is associated with a brief period of hyperphagia before caloric intake and energy balance is restored. This period of homeostatic regulation is associated with a vagally mediated signalling cascade that increases glutamatergic transmission to dorsal motor nucleus of the vagus (DMV) neurons via activation of synaptic NMDA receptors. The present study demonstrates that pharmacological and chemogenetic inhibition of brainstem astrocytes reduced glutamatergic signalling and DMV neuronal excitability, dysregulated gastric motility and tone and emptying, and prevented the regulation of food intake following high-fat diet exposure. Astrocyte regulation of glutamatergic transmission to DMV neurons appears to involve release of the gliotransmitters glutamate and ATP. Understanding the mechanisms involved in caloric regulation may provide critical insights into energy balance as well as into the hyperphagia that develops as these mechanisms are overcome.

Original languageEnglish (US)
Pages (from-to)801-829
Number of pages29
JournalJournal of Physiology
Volume601
Issue number4
DOIs
StatePublished - Feb 15 2023

All Science Journal Classification (ASJC) codes

  • Physiology

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