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Perinatal high fat diet dysregulates GABAergic signaling to vagal efferent motoneurons regulating gastric motility
Author(s) -
Reagan Zachary K,
Browning Kirsteen N
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1157.9
Subject(s) - efferent , dorsal motor nucleus , endocrinology , gabaergic , medicine , motility , vagus nerve , stomach , vagotomy , bicuculline , agonist , chemistry , nucleus ambiguus , biology , antagonist , receptor , stimulation , central nervous system , microbiology and biotechnology , medulla oblongata , afferent
Parasympathetic innervation to the stomach is supplied by dorsal motor nucleus of the vagus (DMV) neurons. Studies have demonstrated that ongoing GABAergic inputs to DMV neurons play a major role in regulating vagal efferent output. The aim of this study was to investigate whether perinatal HFD affects the GABAergic regulation of vagal efferent output to the stomach. Male Sprague Dawley rats were fed a HFD (60%kcal from fat) from E13 until experimentation at 12 weeks of age. Miniaturized strain gauges sutured to the ventral surface of the gastric corpus were used to record gastric motility. The GABA A receptor antagonist, bicuculline methiodide (BMI; 60nl) was microinjected into the dorsal vagal complex and the resulting increase in gastric motility was measured at 3 time points after injection (1.5, 4 and 6.5min) and averaged. Responses were expressed relative to the maximal increase in motility in response to i.v. injection of the non‐selective muscarinic agonist, bethanecol (353pmol; 1ml), which itself was unaffected by diet (9.08±1.20g in control vs 9.27±1.03g in HFD; P>;0.05). In control rats, BMI induced a dose‐dependent increase in gastric motility (3.1±0.6%, 4.8±1.1% and 5.7±1.7% at 25, 50 and 100pmol, n=8,8,4, respectively, P<0.05 for each). In contrast, following HFD, the BMI‐induced increase in gastric motility was significantly attenuated (0.004±0.0001%, 1.2±0.3% and 1.25±0.3% at 25, 50 and 100pmol, n= 4,5,4, respectively, P<0.05 vs control). These data suggest that exposure to a HFD during the perinatal period alters GABAergic activity within brainstem neural circuits controlling gastric functions, which may contribute to the dysregulation of homeostatic reflexes, including appetite and metabolic regulation. Supported by NSF IOS 1148978