Brainstem astrocytes control homeostatic regulation of caloric intake

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

doi:10.1113/jp283566

Cited by 8 publications

(15 citation statements)

References 75 publications

(126 reference statements)

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“…However, there is strong precedence in the literature, including from data in rodent studies examining cholecystokinin (CCK 58 ), prolactin‐releasing peptide (PrRP 59 ) and glucagon‐like peptide‐1 (GLP‐1 60,61 ) signalling, indicating that aversion per se is not necessarily non‐physiological as satiety and nausea/malaise are likely on the same physiological continuum. A recent study by Clyburn and colleagues showed that chemogenetic (GFAP‐hM4DGi) or pharmacological (fluoroacetate) mediated inhibition of astrocytes in the rat dorsal DMV prolongs high‐fat diet induced hyperphagia during the initial homeostatic adjustment to the diet by modulating glutamatergic signalling, resulting in alterations in gastric emptying 62 . While this study focuses on inhibition of DMV astrocyte activity, it supports the notion that specific modulation of these cells in the DVC is sufficient to physiologically impact feeding.…”

Section: Discussionsupporting

confidence: 74%

“…A recent study by Clyburn and colleagues showed that chemogenetic (GFAP-hM4DGi) or pharmacological (fluoroacetate) mediated inhibition of astrocytes in the rat dorsal DMV prolongs high-fat diet induced hyperphagia during the initial homeostatic adjustment to the diet by modulating glutamatergic signalling, resulting in alterations in gastric emptying. 62 While this study focuses on inhibition of DMV astrocyte activity, it supports the notion that specific modulation of these cells in the DVC is sufficient to physiologically impact feeding. In agreement with our data, they observed that in control viral vector injected rats CNO treatment (either 1 mg/kg or 3 mg/kg i.p.)…”

Section: Chemogenetic Activation Of Dvc Astrocytes Suppressed Food In...supporting

confidence: 71%

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Impact of chemogenetic activation of dorsal vagal complex astrocytes in mice on adaptive glucoregulatory responses

Macdonald

Ellacott

Beall

et al. 2023

J Neuroendocrinology

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The dorsal vagal complex (DVC) regulates diverse aspects of physiology including food intake and blood glucose homeostasis. Astrocytes play an active role in regulating DVC function and, by extension, physiological parameters. DVC astrocytes in ex vivo slices respond to low tissue glucose. The response of neurons to low glucose is conditional on intact astrocyte signalling in slice preparations, suggesting astrocytes are primary sensors of glucose deprivation (glucoprivation). Based on these published findings we hypothesised that in vivo DVC astrocyte manipulation with chemogenetics would be sufficient to alter physiological responses that control blood glucose. We found that 2‐h after systemic 2‐DG‐induced glucoprivation there were no observable changes in morphology of glial fibrillary acidic protein (GFAP)‐immunoreactive DVC cells, specifically those in the nucleus of the solitary tract (NTS). Chemogenetic activation of DVC astrocytes was sufficient to suppress nocturnal food intake by reducing both meal size and meal number and this manipulation also suppressed 2‐DG‐induced glucoprivic food intake. Chemogenetic activation of DVC astrocytes did not increase basal blood glucose nor protect against insulin‐induced hypoglycaemia. In male mice, chemogenetic DVC astrocyte activation did not alter glucose tolerance. In female mice, the initial glucose excursion was reduced in a glucose tolerance test, suggesting enhanced glucose absorption. Based on our data and published work, we propose that DVC astrocytes may play an indispensable homeostatic role, that is, are necessary to maintain the function of glucoregulatory neuronal circuitry, but alone their bulk activation is not sufficient to result in adaptive glucoregulatory responses. It is possible that there are state‐dependent effects and/or DVC astrocyte subsets that have this specialised role, but this was unresolvable using the experimental approaches employed here.

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Section: Discussionsupporting

confidence: 74%

Section: Chemogenetic Activation Of Dvc Astrocytes Suppressed Food In...supporting

confidence: 71%

Impact of chemogenetic activation of dorsal vagal complex astrocytes in mice on adaptive glucoregulatory responses

Macdonald

Ellacott

Beall

et al. 2023

J Neuroendocrinology

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“…Below we discuss the evidence supporting these multifaceted effects of hypothalamic astrocytes influencing metabolic function. While this review focuses on metabolic circuits in the hypothalamus, it is important to note important work indicating that astrocytes influence neuronal activity in extrahypothalamic energy balance centers including the dorsal vagal complex (Clyburn et al, 2023; Cui et al, 2022; Reiner et al, 2016; Troadec et al, 2022).…”

Section: Astrocytes and The Regulation Of Synaptic Plasticity And Ene...mentioning

confidence: 99%

Synaptic plasticity and the role of astrocytes in central metabolic circuits

Ameroso,

Rios

2023

WIREs Mechanisms of Disease

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Neural circuits in the brain, primarily in the hypothalamus, are paramount to the homeostatic control of feeding and energy utilization. They integrate hunger, satiety, and body adiposity cues from the periphery and mediate the appropriate behavioral and physiological responses to satisfy the energy demands of the animal. Notably, perturbations in central homeostatic circuits have been linked to the etiology of excessive feeding and obesity. Considering the ever‐changing energy requirements of the animal and required adaptations, it is not surprising that brain‐feeding circuits remain plastic in adulthood and are subject to changes in synaptic strength as a consequence of nutritional status. Indeed, synapse density, probability of presynaptic transmitter release, and postsynaptic responses in hypothalamic energy balance centers are tailored to behavioral and physiological responses required to sustain survival. Mounting evidence supports key roles of astrocytes facilitating some of this plasticity. Here we discuss these synaptic plasticity mechanisms and the emerging roles of astrocytes influencing energy and glucose balance control in health and disease.This article is categorized under: Cancer > Molecular and Cellular Physiology Neurological Diseases > Molecular and Cellular Physiology

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“…This study advances our understanding of how brainstem astrocytes mediate early physiological adaptations to a HFD challenge (Clyburn et al, 2023), with many interesting angles still to pursue. This study focuses on changes in NTS→DMV→gastric neuron circuits, but as significant gastric distention occurs during the hyperphagia immediately following introduction of a HFD, it would be fascinating to examine changes at the vagal-NTS synapse in this paradigm.…”

mentioning

confidence: 94%

“…Understanding the physiological mechanisms underlying satiety may aid development of new therapeutic approaches for disordered eating, particularly in relation to consumption of calorie‐dense foods implicated in the development of obesity. Focusing on a class of cells in the central nervous system called astrocytes, a new comprehensive study by Clyburn and colleagues provides mechanistic insights into the early‐stage molecular and cellular adaptations within the DVC following consumption of a calorie‐rich refined high‐fat diet (HFD) (Clyburn et al., 2023).…”

mentioning

confidence: 99%