TRPV1 Channels and Gastric Vagal Afferent Signalling in Lean and High Fat Diet Induced Obese Mice.

Stephen J Kentish,George Hatzinikolas,Gary A Wittert,Tracey A O’Donnell,Hui Li,Amanda J Page,Claudine L Frisby,Stamatiki Kritas,Daniela Cota

doi:10.1371/journal.pone.0135892

Abstract

AimWithin the gastrointestinal tract vagal afferents play a role in control of food intake and satiety signalling. Activation of mechanosensitive gastric vagal afferents induces satiety. However, gastric vagal afferent responses to mechanical stretch are reduced in high fat diet mice. Transient receptor potential vanilloid 1 channels (TRPV1) are expressed in vagal afferents and knockout of TRPV1 reduces gastro-oesophageal vagal afferent responses to stretch. We aimed to determine the role of TRPV1 on gastric vagal afferent mechanosensitivity and food intake in lean and HFD-induced obese mice.MethodsTRPV1+/+ and -/- mice were fed either a standard laboratory diet or high fat diet for 20wks. Gastric emptying of a solid meal and gastric vagal afferent mechanosensitivity was determined.ResultsGastric emptying was delayed in high fat diet mice but there was no difference between TRPV1+/+ and -/- mice on either diet. TRPV1 mRNA expression in whole nodose ganglia of TRPV1+/+ mice was similar in both dietary groups. The TRPV1 agonist N-oleoyldopamine potentiated the response of tension receptors in standard laboratory diet but not high fat diet mice. Food intake was greater in the standard laboratory diet TRPV1-/- compared to TRPV1+/+ mice. This was associated with reduced response of tension receptors to stretch in standard laboratory diet TRPV1-/- mice. Tension receptor responses to stretch were decreased in high fat diet compared to standard laboratory diet TRPV1+/+ mice; an effect not observed in TRPV1-/- mice. Disruption of TRPV1 had no effect on the response of mucosal receptors to mucosal stroking in mice on either diet.ConclusionTRPV1 channels selectively modulate gastric vagal afferent tension receptor mechanosensitivity and may mediate the reduction in gastric vagal afferent mechanosensitivity in high fat diet-induced obesity.

Highlights

Transient receptor potential (TRP) channels comprise a superfamily of nonselective cation channels [1]
Gastric emptying was delayed in high fat diet mice but there was no difference between Transient receptor potential vanilloid 1 channels (TRPV1)+/+ and -/- mice on either diet
The TRPV1 agonist N-oleoyldopamine potentiated the response of tension receptors in standard laboratory diet but not high fat diet mice

Summary

Introduction

Transient receptor potential (TRP) channels comprise a superfamily of nonselective cation channels [1]. Described as “Thermo TRPs” [2], more recent investigations have shown that they respond to a number of different stimuli. It has been demonstrated that several TRP vanilloid (V) channels, including TRPV1, are mechano- and osmo-sensitive [3]. The TRPV1 channel is best known as a mediator of noxious or painful stimuli [4]. Since its discovery, physiological roles of TRPV1, not associated with pain are becoming apparent, including roles in the regulation of energy balance and intermediary metabolism [5, 6]. It has been suggested that activation of TRPV1 channels might be a target for the management of obesity [7]

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