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


METHODS
TRPV1+/+ 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.


RESULTS
Gastric 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.


CONCLUSIONS
TRPV1 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.
Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia; South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia.
Stephen J
SJ
Kentish
Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia; South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia.
Claudine L
CL
Frisby
Women's & Children's Hospital, Adelaide, South Australia, Australia.
Stamatiki
S
Kritas
Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia; South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia.
Hui
H
Li
Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia; South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia.
George
G
Hatzinikolas
Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia; South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia.
Tracey A
TA
O'Donnell
Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia; South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia; Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Gary A
GA
Wittert
Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia; South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia; Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Amanda J
AJ
Page
D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D004435:Eating / Q000187:drug effects; D004947:Esophagus / Q000187:drug effects / Q000294:innervation; D055786:Gene Knockout Techniques; D008297:Male; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects*; D013270:Stomach / Q000187:drug effects / Q000294:innervation*; D050916:TRPV Cation Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014630:Vagus Nerve / Q000187:drug effects* / Q000473:pathology*
D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse