TY - JOUR
T1 - High fat diet attenuates glucose-dependent facilitation of 5-HT3-mediated responses in rat gastric vagal afferents
AU - Troy, Amanda E.
AU - Simmonds, Sarah S.
AU - Stocker, Sean D.
AU - Browning, Kirsteen N.
N1 - Funding Information:
These studies were supported by NIH (NIDDK) grant DK078364 to K.N.B., and NIH (NHBLI) grant HL113270 and American Heart Association Established Investigator Award to S.D.S.
Publisher Copyright:
© 2016 The Physiological Society.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Glucose regulates the density and function of 5-HT3 receptors on gastric vagal afferent neurones. Since diet-induced obesity attenuates the responsiveness of gastric vagal afferents to several neurohormones, the aim of the present study was to determine whether high fat diet (HFD) compromises the glucose-dependent modulation of 5-HT responses in gastric vagal afferents prior to the development of obesity. Rats were fed control or HFD (14% or 60% kilocalories from fat, respectively) for up to 8 weeks. Neurophysiological recordings assessed the ability of 5-HT to increase anterior gastric vagal afferent nerve (VAN) activity in vivo before and after acute hyperglycaemia, while electrophysiological recordings from gastric-projecting nodose neurones assessed the ability of glucose to modulate the 5-HT response in vitro. Immunocytochemical studies determined alterations in the neuronal distribution of 5-HT3 receptors. 5-HT and cholecystokinin (CCK) induced dose-dependent increases in VAN activity in all rats; HFD attenuated the response to CCK, but not 5-HT. The 5-HT-induced response was amplified by acute hyperglycaemia in control, but not HFD, rats. Similarly, although 5-HT induced an inward current in both control and HFD gastric nodose neurones in vitro, the 5-HT response and receptor distribution was amplified by acute hyperglycaemia only in control rats. These data suggest that, while HFD does not affect the response of gastric-projecting vagal afferents to 5-HT, it attenuates the ability of glucose to amplify 5-HT effects. This suggests that glucose-dependent vagal afferent signalling is compromised by short periods of exposure to HFD well in advance of obesity or glycaemic dysregulation.
AB - Glucose regulates the density and function of 5-HT3 receptors on gastric vagal afferent neurones. Since diet-induced obesity attenuates the responsiveness of gastric vagal afferents to several neurohormones, the aim of the present study was to determine whether high fat diet (HFD) compromises the glucose-dependent modulation of 5-HT responses in gastric vagal afferents prior to the development of obesity. Rats were fed control or HFD (14% or 60% kilocalories from fat, respectively) for up to 8 weeks. Neurophysiological recordings assessed the ability of 5-HT to increase anterior gastric vagal afferent nerve (VAN) activity in vivo before and after acute hyperglycaemia, while electrophysiological recordings from gastric-projecting nodose neurones assessed the ability of glucose to modulate the 5-HT response in vitro. Immunocytochemical studies determined alterations in the neuronal distribution of 5-HT3 receptors. 5-HT and cholecystokinin (CCK) induced dose-dependent increases in VAN activity in all rats; HFD attenuated the response to CCK, but not 5-HT. The 5-HT-induced response was amplified by acute hyperglycaemia in control, but not HFD, rats. Similarly, although 5-HT induced an inward current in both control and HFD gastric nodose neurones in vitro, the 5-HT response and receptor distribution was amplified by acute hyperglycaemia only in control rats. These data suggest that, while HFD does not affect the response of gastric-projecting vagal afferents to 5-HT, it attenuates the ability of glucose to amplify 5-HT effects. This suggests that glucose-dependent vagal afferent signalling is compromised by short periods of exposure to HFD well in advance of obesity or glycaemic dysregulation.
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U2 - 10.1113/JP271558
DO - 10.1113/JP271558
M3 - Article
C2 - 26456775
AN - SCOPUS:84952832034
SN - 0022-3751
VL - 594
SP - 99
EP - 114
JO - Journal of Physiology
JF - Journal of Physiology
IS - 1
ER -