Physiology Shorts: Perinatal high-fat diet exposure alters oxytocin and corticotropin

In this Physiology Shorts video Kirsteen Browning and Kaitlin Carson (Department of Neural and Behavioral Sciences, Pennsylvania State College of Medicine, Hershey, PA, USA) talk about their study: Perinatal high-fat diet exposure alters oxytocin and corticotropin releasing factor inputs onto vagal neurocircuits controlling gastric motility.
Read more in The Journal of Physiology:
Perinatal high-fat diet exposure alters oxytocin and corticotropin releasing factor inputs onto vagal neurocircuits controlling gastric motility.
Kirsteen N. Browning et al.
601 (14), pp. 2853-2875
physoc.onlinelibrary.wiley.co...
Transcript:
KIRSTEEN: Hello, my name is Kirsteen Browning. I am a professor in the Department of Neural and Behavioral Sciences at Penn State College of Medicine in Hershey Pennsylvania
KAITLIN: And my name is Kaitlin Carson, a PhD candidate at the Penn State College of Medicine.
KIRSTEEN: Our group works on brainstem control of autonomic function, particularly gastrointestinal functions, and how those vagally mediated reflexes are altered by different conditions such as diet or stress.
KAITLIN: Offspring exposed to a high-fat diet exposure during the perinatal period (AKA in utero and during early postnatal life) have been shown to be predisposed to developing metabolic disorders, anxiety and mood disorders, as well as gastric dysmotility. Because of this, our group was curious to see how perinatal high fat diet exposure would impact the development of vagal neurocircuits that modulate gastrointestinal motility. Specifically, we were interested in the CRF and oxytocin projections from the paraventricular nucleus of the hypothalamus to the dorsal vagal complex, as these circuits play important roles in modulating your gastric motility in response to stress.
To do this, first we first assessed the offspring’s response to stress, using a 2-hour restraint stress. Following which we evaluated their vagal gastric response to stress through an in vivo gastric emptying assay. Interestingly, we found their basal gastric emptying rates were already delayed, and did not further slow after a stress exposure, as you would expect. This suggested to us that there has been some maladaptive neuroplasticity in vagal circuits that needed to be investigated.
So, we conducted neuronal tracing experiments and found that perinatal high fat diet exposure increased CRF neurons in the PVN, while leading to decreased OXT innervation in the DMV.
I then performed in vivo recordings of gastric motility. Normally, oxytocin microinjection directly into the DMV leads to a gastric relaxation. However, remarkably, oxytocin injection in a perinatal high fat diet rat led to a gastric contraction. I was able to induce gastric relaxation in perinatal high fat diet rats by pretreating them with astressin, a CRF receptor antagonist. This would suggest the perinatal high fat diet rats were already “stressed” via tonic CRF receptor activation.
Lastly, these in vivo results were corroborated when I performed in vitro whole cell patch clamp electrophysiology on DMV neurons, who displayed altered GABA currents in response to oxytocin application. Like before, I was able to normalize these responses when I blocked the CRF receptors, suggesting tonic activation of CRF1 receptors at this synapse.
Identifying a mechanism driving these gastric changes is important as chronic delays in gastric emptying can lead to nausea, bloating, abdominal pain and early satiety, all of which are exacerbated by dysregulated brain-gut reflexes.
Importantly, the current study has shown that just diet alone, in the absence of maternal obesity, is sufficient to drive these changes and therefore applicable to all mothers.
KIRSTEEN: Thank you for taking to time to learn more about our study. The full paper was published in The Journal of Physiology in Volume 601, Issue 14. Please feel free to contact me if you have any further questions.