Oral Presentation Australian & New Zealand Obesity Society 2014 Annual Scientific Meeting

Gastric vagal afferent satiety signals are modulated by endogenous and exogenous oestradiol (#110)

Stephen J Kentish 1 , Claudine L Frisby 1 , Gary A Wittert 1 , Amanda J Page 1 2
  1. Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia
  2. Royal Adelaide Hospital, Adelaide, SA, Australia

Food intake is reduced during oestrus in rodents through a reduction in meal size. This is just after the peak in plasma oestradiol (E2) levels. Exogenous E2 reduces meal size and overall food intake in ovariectomized rats 1 . Whilst E2 can act on the arcuate nucleus to reduce food intake, the E2 receptors, ERα, ERβ and GPR30 are also expressed in the cell bodies of vagal afferents located in the nodose ganglia 2 . Furthermore, E2 can sensitize cultured vagal neurons 3 . This suggests there may also be a peripheral site of action on food intake because activation of mechanosensitive gastric vagal afferents (GVAs) induces satiety. However, whether E2 can act on GVAs to modulate satiety signals and whether the reduction in food intake during oestrus has a vagal origin is unknown.

The oestrous cycle stage of 8wk old female C57BL/6 mice was determined using vaginal cell cytometry (N=3/cycle stage) 4 . Single fibre recordings of GVA mechanoreceptors were made 5  in the absence and presence of E2 (10-1000pM). Recordings were also taken after pre-incubation with the ERα selective antagonist, fulvestrant. Nodose ganglia ERα, ERβ and GPR30 mRNA levels were quantified by quantitative RT-PCR.

Tension receptor response to stretch (3g) was increased in mice currently in oestrus (p<0.05 vs. dioestrus). There was no difference in the response of mucosal receptors to mucosal stroking (50mg) at any oestrous cycle stage. E2 dose dependently potentiated mucosal and tension receptor responses to mucosal stroking (10-1000mg, p<0.001) and stretch (1–5g, p<0.05) respectively. The potentiation caused by E2 on tension and mucosal receptors was blocked by pre-incubation with fulvestrant. All three E2 receptors were present in the nodose ganglia, but there was 60 and 25 times more ERα mRNA present than ERβ or GPR30 respectively (p<0.001).

Together this data suggests that the reduction in food intake observed during the oestrus stage may be due to an ERα mediated E2 induced potentiation of tension receptor mechanosensitivity.

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