title: Exposure to a high fat diet during the perinatal period alters vagal motoneurone excitability, even in the absence of obesity.
abstract: Obesity is recognized as being multifactorial in origin, involving both genetic and environmental factors. The perinatal period is known to be critically important in the development of neural circuits responsible for energy homeostasis and the integration of autonomic reflexes. Diet-induced obesity alters the biophysical, pharmacological and morphological properties of vagal neurocircuits regulating upper gastrointestinal tract functions, including satiety. Less information is available, however, regarding the effects of a high fat diet (HFD) itself on the properties of vagal neurocircuits. The present study was designed to test the hypothesis that exposure to a HFD during the perinatal period alters the electrophysiological, pharmacological and morphological properties of vagal efferent motoneurones innervating the stomach. Our data indicate that perinatal HFD decreases the excitability of gastric-projecting dorsal motor nucleus neurones and dysregulates neurotransmitter release from synaptic inputs and that these alterations occur prior to the development of obesity. These findings represent the first direct evidence that exposure to a HFD modulates the processing of central vagal neurocircuits even in the absence of obesity. The perinatal period is critically important to the development of autonomic neural circuits responsible for energy homeostasis. Vagal neurocircuits are vital to the regulation of upper gastrointestinal functions, including satiety. Diet-induced obesity modulates the excitability and responsiveness of both peripheral vagal afferents and central vagal efferents but less information is available regarding the effects of diet per se on vagal neurocircuit functions. The aims of this study were to investigate whether perinatal exposure to a high fat diet (HFD) dysregulated dorsal motor nucleus of the vagus (DMV) neurones, prior to the development of obesity. Whole cell patch clamp recordings were made from gastric-projecting DMV neurones in thin brainstem slices from rats that were exposed to either a control diet or HFD from pregnancy day 13. Our data demonstrate that following perinatal HFD: (i) DMV neurones had decreased excitability and input resistance with a reduced ability to fire action potentials; (ii) the proportion of DMV neurones excited by cholecystokinin (CCK) was unaltered but the proportion of neurones in which CCK increased excitatory glutamatergic synaptic inputs was reduced; (iii) the tonic activation of presynaptic group II metabotropic glutamate receptors on inhibitory nerve terminals was attenuated, allowing modulation of GABAergic synaptic transmission; and (iv) the size and dendritic arborization of gastric-projecting DMV neurones was increased. These results suggest that perinatal HFD exposure compromises the excitability and responsiveness of gastric-projecting DMV neurones, even in the absence of obesity, suggesting that attenuation of vago-vagal reflex signalling may precede the development of obesity.
authors.affiliation: Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA 17033, USA.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Bhagat
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Fortna
authors.forename: Kirsteen N
authors.initials: KN
authors.lastname: Browning
mesh_terms: D000200:Action Potentials; D000375:Aging / Q000502:physiology*; D000818:Animals; D001933:Brain Stem / Q000502:physiology; D059305:Diet, High-Fat; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009046:Motor Neurons / Q000502:physiology*; D009765:Obesity / Q000503:physiopathology; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate; D013270:Stomach / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D024642:Potassium Channels, Voltage-Gated; D018094:Receptors, Metabotropic Glutamate