Oral Presentation Australian & New Zealand Obesity Society Annual Scientific Meeting 2013

The role of TRPV1 channels in gastric vagal afferent satiety signalling in lean and obese mice. (#128)

Amanda J Page 1 2 , Stephen J Kentish 1 , George Hatzinikolas 1 , Tracey A ODonnell 1 , Gary A Wittert 1
  1. University of Adelaide, Adelaide, SA, Australia
  2. Nutrition and Metabolism, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia

Aims: TRPV1 deficient mice are resistant to high fat diet induced obesity (HF-DIO)1 . Activation of mechanosensitive gastric vagal afferents (GVAs) induces satiety. Responses to mechanical stretch are reduced in HF-DIO2. TRPV1 channels are expressed in GVAs3. Knockout of TRPV1 reduces gastroesophageal responses to stretch4. The effect of HF-DIO on TRPV1 mediated GVA mechanosensitivity is unknown. We aimed to determine the role of TRPV1 on GVA mechanosensitivity and food intake in lean and DIO mice.

Methods: 8wk old male TRPV1+/+ (WT) and -/- (KO) mice were fed either standard (SLD; 12% energy from fat) or HF chow (60% energy from fat) for 20wks (N=10/group). Food intake and weight were monitored. At 20wks, single fibre in vitro recordings of GVA mechanoreceptors were obtained.

Results: GVA tension receptor response to stretch (1–5g) was reduced and food intake (gms) increased in KO-SLD mice (p<0.001 v WT-SLD). Tension receptor responses to stretch decreased in WT-HF (p<0.001), but not KO mice. Food intake (gms) was similar in the KO and WT-HF mice. Weight gain, on either diet was less in KO than WT mice (p<0.01). Energy intake (Kcals/gram weight gained) was 3 fold greater in the KO-HF mice (p<0.001 v WT-HF). TRPV1 KO had no effect on the response of gastric mucosal receptors to mucosal stroking in mice on either diet.

Conclusion: TRPV1 channels modulate GVA tension receptor mechanosensitivity and may mediate the reduction in GVA mechanosensitivity in response to HF-DIO, an effect not seen in the KO mice. The observation that food intake in grams was the same rather than less (as expected) in the KO vs WT mice may be a consequence of the marked decrease in metabolic efficiency in the KO in response to the HFD.
Funding: Gum Bequest, Royal Adelaide Hospital

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