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

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          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.

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          Author and article information

          Am J Physiol Gastrointest Liver Physiol
          Am. J. Physiol. Gastrointest. Liver Physiol
          Am J Physiol Gastrointest Liver Physiol
          American Journal of Physiology - Gastrointestinal and Liver Physiology
          American Physiological Society (Bethesda, MD )
          1 May 2018
          25 January 2018
          1 May 2019
          : 314
          : 5
          : G623-G634
          Department of Neural and Behavioral Sciences, Penn State College of Medicine , Hershey, Pennsylvania
          Author notes
          Address for reprint requests and other correspondence: K. Browning, Dept. of Neural and Behavioral Science, Penn State Coll. of Medicine, 500 University Dr., MC H109, Hershey, PA 17033 (e-mail: kbrowning@ 123456pennstatehealth.psu.edu ).
          PMC6008060 PMC6008060 6008060 GI-00395-2017 GI-00395-2017
          Copyright © 2018 the American Physiological Society
          Funded by: HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 10.13039/100000062
          Award ID: 78364
          Funded by: NSF | BIO | Division of Integrative Organismal Systems (IOS) 10.13039/100000154
          Award ID: 1148978
          Research Article
          Neurogastroenterology and Motility


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