Acute high-fat diet upregulates glutamatergic signaling in the dorsal motor nucleus of the vagus

Abstract

Obesity is associated with dysregulation of vagal neurocircuits controlling gastric functions, including food intake and energy balance. In the short term, however, caloric intake is regulated homeostatically although the precise mechanisms responsible are unknown. The present study examined the effects of acute high-fat diet (HFD) on glutamatergic neurotransmission within central vagal neurocircuits and its effects on gastric motility. Sprague-Dawley rats were fed a control or HFD diet (14% or 60% kcal from fat, respectively) for 3-5 days. Whole cell patch-clamp recordings and brainstem application of antagonists were used to assess the effects of acute HFD on glutamatergic transmission to dorsal motor nucleus of the vagus (DMV) neurons and subsequent alterations in gastric tone and motility. After becoming hyperphagic initially, caloric balance was restored after 3 days following HFD exposure. In control rats, the non- N-methyl-d-aspartate (NMDA) receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX), but not the NMDA receptor antagonist, amino-5-phosphonopentanoate (AP5), significantly decreased excitatory synaptic currents and action potential firing rate in gastric-projecting DMV neurons. In contrast, both AP5 and DNQX decreased excitatory synaptic transmission and action potential firing in acute HFD neurons. When microinjected into the brainstem, AP5, but not DNQX, decreased gastric motility and tone in acute HFD rats only. These results suggest that acute HFD upregulates NMDA receptor-mediated currents, increasing DMV neuronal excitability and activating the vagal efferent cholinergic pathway, thus increasing gastric tone and motility. Although such neuroplasticity may be a persistent adaptation to the initial exposure to HFD, it may also be an important mechanism in homeostatic regulation of energy balance. NEW & NOTEWORTHY Vagal neurocircuits are critical to the regulation of gastric functions, including satiation and food intake. Acute high-fat diet upregulates glutamatergic signaling within central vagal neurocircuits via activation of N-methyl-d-aspartate receptors, increasing vagal efferent drive to the stomach. Although it is possible that such neuroplasticity is a persistent adaptation to initial exposure to the high-fat diet, it may also play a role in the homeostatic control of feeding.

Acupuncture at Gastric Back‐Shu and Front‐Mu Acupoints Enhances Gastric Motility via the Inhibition of the Glutamatergic System in the Hippocampus

“…For example, microinjection of glutamate into the nucleus ambiguus (NA) partially inhibits gastric motility through the activation of the NMDAR-NO pathway, and microinjection of glutamate into the hippocampus inhibits gastric motility Evidence-Based Complementary and Alternative Medicine through NMDAR [35,36]. Moreover, one study showed that acute high-fat diet upregulated glutamatergic signalling in the DMV, thus increasing gastric motility [17]. ese studies indicated that the change of the glutamatergic system could affect gastric motility.…”

“…Some studies have indicated the existence of many gastric dilatation-sensitive neurons in the hippocampus [16], but the types of these neurons are unclear. In addition, glutamatergic signalling in the dorsal motor nucleus of the vagus (DMV) via the activation of N-methyl-daspartate receptors (NMDAR) increases gastric motility [17]; NMDAR is widely distributed in the hippocampus [18]. e stimulation of NMDARs results in calcium influx, the activation of neuronal nitric oxide synthase (nNOS), and an increase in the content of nitric oxide (NO) [19,20].…”

Advances in the physiology of gastric emptying

“…However, further studies are needed to elucidate the distinct roles of GABA neurons in NTS and DMV in gastric motility. NTS‐GABA and NTS‐non‐GABA inhibitory neurons and NTS‐GLUT excitatory neurons exert an inhibitory and excitatory effect, respectively, on the DMV‐C‐e neurons …”

“…NTS-GABA and NTS-non-GABA inhibitory neurons and NTS-GLUT excitatory neurons exert an inhibitory and excitatory effect, respectively, on the DMV-C-e neurons. 73 Moreover, within the NTS, the GABA, non-GABA, and GLUT neurons are interconnected. 74 NTS-CC-e neurons may also act to inhibit DMV-C-e neurons via the α2-receptors.…”

The pharmacokinetic parameters and the effect of a single and repeated doses of memantine on gastric myoelectric activity in experimental pigs

“…Memantine is believed to block the current flow through channels of NMDA glutamate receptor [33,34]. NMDA receptors are involved in the regulation of many gastric functions: 1) hydrochloric acid production [35], 2) glutamatergic, cholinergic and non-cholinergic pathways [36][37][38], 3) ghrellin mediated processes [12], 4) visceral pain [39], 5) chronic Helicobacter pylori infection [40], 6) gastric accommodation and emptying [41] and other. NMDA receptors also participate in the brain-gut axis regulation [42] and function of the lower oesophageal sphincter [43].…”