Background: Previous studies suggest an increased inhibition of dorsal motor nucleus

Diet-induced obesity induces peripheral inflammation accompanied by a loss of myenteric neurons. Few studies, however, have investigated the effects of a high fat diet (HFD) on either the development of myenteric neurons or prior to the occurrence of obesity. The present study assessed the effects of maternal HFD on the density and neurochemical phenotype of myenteric ganglia in the upper gastrointestinal tract. Sprague-Dawley rats were fed either a control or HFD (14% or 60% kcal from fat, respectively) from embryonic day 13; the fundus, corpus and duodenum were fixed thereafter at postnatal 2, 4, 6 and 12 weeks of age for subsequent immunohistochemical studies. While myenteric ganglion size did not differ throughout the study, HFD exposure decreased the number of nitrergic neurons by 6 weeks of age in all regions. This decrease was accompanied by a loss of PGP-immunoreactive neurons, suggesting a decline in myenteric neuronal number. HFD also increased myenteric plexus glial cell density in all regions by 4 weeks of age. These changes occurred in the absence of an increase in serum or gastric inflammatory markers. The present study suggests that exposure to a HFD during the perinatal time period results in glial proliferation and loss of inhibitory nitrergic neurons prior to the onset of obesity, suggesting that dietary alterations may affect gastrointestinal functions independently of increased adiposity or glycemic dysregulation.

The gastrointestinal tract receives extrinsic innervation from both the sympathetic and parasympathetic nervous systems, which regulate and modulate the function of the intrinsic (enteric) nervous system. The stomach and upper gastrointestinal tract in particular are heavily influenced by the parasympathetic nervous system, supplied by the vagus nerve, and disruption of vagal sensory or motor functions results in disorganized motility patterns, disrupted receptive relaxation and accommodation, and delayed gastric emptying, amongst others. Studies from several laboratories have shown that the activity of vagal efferent motoneurons innervating the upper GI tract is inhibited tonically by GABAergic synaptic inputs from the adjacent nucleus tractus solitarius. Disruption of this influential central GABA input impacts vagal efferent output, hence gastric functions, significantly. The purpose of this review is to describe the development, physiology, and pathophysiology of this functionally dominant inhibitory synapse and its role in regulating vagally determined gastric functions.