Perinatal high fat diet exposure alters oxytocin and corticotropin releasing factor inputs onto vagal neurocircuits controlling gastric motility
Authors: Carson Kaitlin , Alvarez Jared , Mackley Jasmine , Browning Kirsteen 
Published: May 2023

Perinatal high fat diet (pHFD) exposure alters the development of vagal neurocircuits that control gastrointestinal (GI) motility and reduce stress resiliency in offspring. Stress causes a delay in gastric emptying that is, at least in part, vagally dependent. 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 gastric response to stress, but how these descending inputs are altered following pHFD exposure is unknown. The present study used in vivo recordings of gastric tone and motility, in vivo assays of gastric emptying rates, in vitro electrophysiological recordings from DMV neurons in brainstem slices, and retrograde tracing experiments to investigate the hypothesis that pHFD alters descending PVN-DMV inputs, dysregulating vagal efferent control of gastric functions.Basal gastric emptying rates were significantly delayed in pHFD rats (76.87±22.07min vs. 57.63±6.94min for control, p=0.0338; via two-tailed unpaired t-test), which were also unable to respond to acute stress (2hr restraint) with a further delay in gastric emptying (66.81±9.30 minutes) unlike control rats (66.07±10.79 minutes). Neuronal tracing experiments showed that pHFD reduced PVNOXT-DMV projections (10.5±6.6 control vs. 3.3±2.7 pHFD cells/section, p=0.0032; via two-tailed unpaired t-test) but increased PVNCRF-DMV projections (9.83±5.184 control vs. 19.85±12.89 pHFD cells/section, p=0.0158; via two-tailed unpaired t-test). In vitro whole cell patch clamp recordings demonstrated that OXT (100nM) application decreased the frequency of miniature inhibitory currents (mIPSCs) in pHFD but not control DMV neurons (65.18%±27.30 vs 97.89%±15.36 respectively, p=0.0101; via two-tailed unpaired t-test). Moreover, the CRF antagonist, astressin (1μM) increased mIPSC frequency in pHFD but not control DMV neurons (129.9±42.95% vs. 82.87±5.35% respectively, p=0.0411 via unpaired two-tailed t-test) suggesting pHFD PVNCRF-DMV inputs are tonically active. In vivo recordings of gastric tone showed that DMV microinjection of OXT (150pmols/60nl) decreased gastric tone in control rats, but increased tone in pHFD rats (control: -134.2±79.06 mg vs. pHFD: +142.2±244.5 mg, p=0.0070; via two-tailed unpaired t-test). Lastly, in pHFD rats, 4th ventricular astressin (10μg/2μl) application restored the appropriate gastroinhibitory response to OXT (baseline: +142.2±244.5 mg vs astressin: -75.67±271.67 mg, p=0.0015; via two-tailed paired t-test).Collectively, these results indicate that pHFD exposure upregulates, and tonically activates, PVNCRF-DMV inputs. Together with the reduced PVNOXT-DMV innervation, this leads to gastric dysmotility, maladaptive gastric stress responses and reduced stress resiliency in pHFD offspring.

NIH DK111667

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.