Diet‐induced adaptation of vagal afferent function

Abstract

Non-technical summary Obesity is the result of a disruption in the maintenance of energy balance such that energy intake exceeds expenditure. Why this occurs is unknown. We show that after food deprivation or consumption of a high fat diet gastric vagal afferent responses to distension are reduced. In addition, the effect of the orexigenic peptide ghrelin is enhanced. Thus the satiety signal is reduced not only after food deprivation but also after a high fat diet. This reduction in satiety signalling may explain the increase in energy intake and disruption in maintenance of energy balance in obesity.Abstract Afferent signals from the stomach play an important role in inhibition of food intake during a meal. The gastric hormone ghrelin can influence gastric satiety signalling by altering the sensitivity of gastric vagal afferents. Changes in diet, including food restriction and high fat diet (HFD) alter satiety signalling. We hypothesised that the function of gastric vagal afferent endings are affected by both a period of food restriction and a high fat diet, and that the inhibitory effect of ghrelin on vagal afferents is influenced by the different feeding conditions. We found that both fasting and HFD reduced the responses of gastric vagal tension receptors to distension, but not responses of mucosal receptors to mucosal contact. We traced vagal afferents anterogradely to their terminals in the mucosa where we found they were in close apposition to ghrelin-containing cells. Ghrelin receptor mRNA was expressed in vagal afferent cell bodies of the nodose ganglia, and increased in response to caloric restriction, but decreased in HFD mice. In control mice, ghrelin decreased the sensitivity of tension but not mucosal receptors. After caloric restriction or high fat diet, ghrelin inhibited mucosal receptors, and the inhibition of mechanosensitive tension receptors was enhanced. Therefore, both caloric restriction and HFD decrease mechanosensory vagal afferent signals, and augment the inhibitory effect of ghrelin on vagal afferents, but different mechanisms mediate the short-and longer-term changes. Abbreviations GHS, growth hormone secretagogue; HFD, high fat diet; SLD, standard laboratory diet; WGA-HRP, wheat-germ agglutinin-conjugated horseradish peroxidase.

Extrinsic primary afferent signalling in the gut

“…Responses of IGLEs to ghrelin show marked plasticity, being upregulated after overfeeding. 40 Such peripheral chemosensitivity might reflect the fact that these receptors have important roles at the endings of these sensory neurons in the central nervous system. Alternatively, there might be pathophysiological scenarios in which the hormone ghrelin or the transmitters glutamate, GABA or ATP accumulate within the gut wall to levels that modulate firing of these mechanoreceptors, perhaps after release from enteric nerve terminals.…”

Modulacja kurczliwości żołądka — nowa metoda leczenia cukrzycy typu 2 u osób z otyłością

“…Te słabe impulsy, pojawiające się głównie w początkowej fazie jedzenia, są odpowiedzialne za kurczliwość żołądka. Jej wzrost, będący następstwem rozciągnięcia tego organu, jest z kolei źródłem impulsów przewodzonych za pośrednictwem włókien aferentnych nerwu błędnego do jądra pasma samotnego (NTS, nucleus tractus solitarii), pola najdalszego (AP, area postrema) i ośrodków regulatorowych w mózgu celem wytworzenia uczucia sytości [12,13]. Wyniki pierwszych badań prowadzonych na zwierzętach wykazały, że możliwe jest umieszczenie w ścianie żołądka elektrod pozwalających na odbiór sygnałów elektrycznych powstających w trakcie jedzenia, zwłaszcza na początku posiłku, i ich potencjalizacja z następowym zwiększeniem kurczliwości i amplitudy bodźców przesyłanych za pomocą włókien nerwu błędnego do mózgu [14,15].…”

“…[24] Osoby otyłe (6 mężczyzn, 7 kobiet), BMI 37,2 ± 1,0 kg/m 2 , z cukrzycą typu 2 źle kontrolowaną z użyciem leków doustnych (HbA 1c ≥ 7%), (13) Implantacja generatora pulsów, obserwacja 3-miesięczna U 13 badanych, którzy ukończyli 3-miesięczny cykl leczenia, stwierdzono znamienne obniżenie HbA 1c z 8,0 ± 0,2% do 6,9 ± 0,1% (p < 0,05), a także spadek stężenia glukozy na czczo ze 175 ± 6 mg/dl do 127 ± 8 mg/dl (p < 0,05). Poprawie kontroli glikemii towarzyszyły spadek masy ciała ze 104,4 ± 4,4 kg do 99,7 ± 4,8 kg i obwodu talii ze 122,3 ± 3,2 cm do 117,0 ± 3,0 cm PRACE POGLĄDOWE stężeniem HbA 1c .…”

“…This increase in the force of gastric contractions relating to the stomach distension increases vagal afferent activity. Impulses are sent to the regulatory centres in the brain (Nucleus Tractus Solitarius and Area Postrema) and thus contribute to generating the sensation of satiety [12,13]. In the first studies in animals the implantation of gastric leads enabled the detection of the signals generated in the stomach at the beginning of foot intake and to enhance antral contractions and vagal afferent signalling with synchronised electrical stimulation [14,15].…”

“…Bohdalian A et al [24] Obese subjects (6 male, 7 female), BMI 37.2 ± 1.0 kg/m 2 , with type 2 diabetes treated with oral antidiabetic drugs but with poor glycaemic control (HbA 1c ≥ 7%), (13) Implantation of pulse generator, 3 month follow-up 13 subjects that had completed 3 months of treatment showed a significant reduction in HbA 1c from 8.0 ± 0.2% to 6.9 ± 0.1% (p < 0.05), whereas fasting blood glucose decreased from 175±6 mg/dL to 127 ± 8 mg/dL (p < 0.05).…”