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J Physiol. 2011 Jun 1;589(Pt 11):2857-70. doi: 10.1113/jphysiol.2010.204594. Epub 2011 Mar 21.

Impaired intestinal afferent nerve satiety signalling and vagal afferent excitability in diet induced obesity in the mouse.

Author information

1
Departments of Medicine and Physiology, Gastrointestinal Diseases Research Unit (GIDRU) Wing, Kingston General Hospital, 76 Stuart Street, Kingston, Ontario, Canada K7L2V7.

Abstract

Gastrointestinal vagal afferents transmit satiety signals to the brain via both chemical and mechanical mechanisms. There is indirect evidence that these signals may be attenuated in obesity. We hypothesized that responses to satiety mediators and distension of the gut would be attenuated after induction of diet induced obesity. Obesity was induced by feeding a high fat diet (60% kcal from fat). Low fat fed mice (10% kcal from fat) served as a control. High fat fed mice were obese, with increased visceral fat, but were not hyperglycaemic. Recordings from jejunal afferents demonstrated attenuated responses to the satiety mediators cholecystokinin (CCK, 100 nm) and 5-hydroxytryptamine (5-HT, 10 μm), as was the response to low intensity jejunal distension, while responses to higher distension pressures were preserved. We performed whole cell patch clamp recordings on nodose ganglion neurons, both unlabelled, and those labelled by fast blue injection into the wall of the jejunum. The cell membrane of both labelled and unlabelled nodose ganglion neurons was less excitable in HFF mice, with an elevated rheobase and decreased number of action potentials at twice rheobase. Input resistance of HFF neurons was also significantly decreased. Calcium imaging experiments revealed reduced proportion of nodose ganglion neurons responding to CCK and 5-HT in obese mice. These results demonstrate a marked reduction in afferent sensitivity to satiety related stimuli after a chronic high fat diet. A major mechanism underlying this change is reduced excitability of the neuronal cell membrane. This may explain the development of hyperphagia when a high fat diet is consumed. Improving sensitivity of gastrointestinal afferent nerves may prove useful to limit food intake in obesity.

PMID:
21486762
PMCID:
PMC3112560
DOI:
10.1113/jphysiol.2010.204594
[Indexed for MEDLINE]
Free PMC Article

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