TY - JOUR
T1 - Perinatal high-fat diet exposure alters oxytocin and corticotropin releasing factor inputs onto vagal neurocircuits controlling gastric motility
AU - Carson, Kaitlin E.
AU - Alvarez, Jared
AU - Mackley, Jasmine Q.
AU - Travagli, R. Alberto
AU - Browning, Kirsteen N.
N1 - Publisher Copyright:
© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.
PY - 2023/7/15
Y1 - 2023/7/15
N2 - Abstract: Perinatal high-fat diet (pHFD) exposure alters the development of vagal neurocircuits that control gastrointestinal (GI) motility and reduce stress resiliency in offspring. Descending oxytocin (OXT; prototypical anti-stress peptide) and corticotropin releasing factor (CRF; prototypical stress peptide) inputs from the paraventricular nucleus (PVN) of the hypothalamus to the dorsal motor nucleus of the vagus (DMV) modulate the GI stress response. How these descending inputs, and their associated changes to GI motility and stress responses, are altered following pHFD exposure are, however, unknown. The present study used retrograde neuronal tracing experiments, cerebrospinal fluid extraction, in vivo recordings of gastric tone, motility and gastric emptying rates, and in vitro electrophysiological recordings from brainstem slice preparations to investigate the hypothesis that pHFD alters descending PVN–DMV inputs and dysregulates vagal brain–gut responses to stress. Compared to controls, rats exposed to pHFD had slower gastric emptying rates and did not respond to acute stress with the expected delay in gastric emptying. Neuronal tracing experiments demonstrated that pHFD reduced the number of PVNOXT neurons that project to the DMV, but increased PVNCRF neurons. Both in vitro electrophysiology recordings of DMV neurons and in vivo recordings of gastric motility and tone demonstrated that, following pHFD, PVNCRF–DMV projections were tonically active, and that pharmacological antagonism of brainstem CRF1 receptors restored the appropriate gastric response to brainstem OXT application. These results suggest that pHFD exposure disrupts descending PVN–DMV inputs, leading to a dysregulated vagal brain–gut response to stress. (Figure presented.). Key points: Maternal high-fat diet exposure is associated with gastric dysregulation and stress sensitivity in offspring. The present study demonstrates that perinatal high-fat diet exposure downregulates hypothalamic–vagal oxytocin (OXT) inputs but upregulates hypothalamic–vagal corticotropin releasing factor (CRF) inputs. Both in vitro and in vivo studies demonstrated that, following perinatal high-fat diet, CRF receptors were tonically active at NTS–DMV synapses, and that pharmacological antagonism of these receptors restored the appropriate gastric response to OXT. The current study suggests that perinatal high-fat diet exposure disrupts descending PVN–DMV inputs, leading to a dysregulated vagal brain–gut response to stress.
AB - Abstract: Perinatal high-fat diet (pHFD) exposure alters the development of vagal neurocircuits that control gastrointestinal (GI) motility and reduce stress resiliency in offspring. Descending oxytocin (OXT; prototypical anti-stress peptide) and corticotropin releasing factor (CRF; prototypical stress peptide) inputs from the paraventricular nucleus (PVN) of the hypothalamus to the dorsal motor nucleus of the vagus (DMV) modulate the GI stress response. How these descending inputs, and their associated changes to GI motility and stress responses, are altered following pHFD exposure are, however, unknown. The present study used retrograde neuronal tracing experiments, cerebrospinal fluid extraction, in vivo recordings of gastric tone, motility and gastric emptying rates, and in vitro electrophysiological recordings from brainstem slice preparations to investigate the hypothesis that pHFD alters descending PVN–DMV inputs and dysregulates vagal brain–gut responses to stress. Compared to controls, rats exposed to pHFD had slower gastric emptying rates and did not respond to acute stress with the expected delay in gastric emptying. Neuronal tracing experiments demonstrated that pHFD reduced the number of PVNOXT neurons that project to the DMV, but increased PVNCRF neurons. Both in vitro electrophysiology recordings of DMV neurons and in vivo recordings of gastric motility and tone demonstrated that, following pHFD, PVNCRF–DMV projections were tonically active, and that pharmacological antagonism of brainstem CRF1 receptors restored the appropriate gastric response to brainstem OXT application. These results suggest that pHFD exposure disrupts descending PVN–DMV inputs, leading to a dysregulated vagal brain–gut response to stress. (Figure presented.). Key points: Maternal high-fat diet exposure is associated with gastric dysregulation and stress sensitivity in offspring. The present study demonstrates that perinatal high-fat diet exposure downregulates hypothalamic–vagal oxytocin (OXT) inputs but upregulates hypothalamic–vagal corticotropin releasing factor (CRF) inputs. Both in vitro and in vivo studies demonstrated that, following perinatal high-fat diet, CRF receptors were tonically active at NTS–DMV synapses, and that pharmacological antagonism of these receptors restored the appropriate gastric response to OXT. The current study suggests that perinatal high-fat diet exposure disrupts descending PVN–DMV inputs, leading to a dysregulated vagal brain–gut response to stress.
UR - http://www.scopus.com/inward/record.url?scp=85159638116&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85159638116&partnerID=8YFLogxK
U2 - 10.1113/JP284726
DO - 10.1113/JP284726
M3 - Article
C2 - 37154244
AN - SCOPUS:85159638116
SN - 0022-3751
VL - 601
SP - 2853
EP - 2875
JO - Journal of Physiology
JF - Journal of Physiology
IS - 14
ER -