reduction in the response to stretch. This
suggests that the dampened satiety signalling
in cases of obesity induced by a high-fat diet is
due to disrupted TRPV1-mediated responses
within nerves innervating the stomach.
If we can restore or improve the func-
tion of TRPV1 channels in these nerves
then perhaps we can enhance the feelings
of fullness and terminate food intake sooner.
This is particularly relevant because an indi-
vidual’s metabolic response after weight loss
does not return to its pre-obesity state.
If mice are placed back on a normal diet for
an equivalent amount of time that they were
on the high-fat diet then the response to stretch
is not returned to normal; the dampened
response of nerves innervating the stomach to
stretch remains. Therefore it’s possible that the
disruption in function of TRPV1 channels is
maintained even after weight loss.
This may be one of the reasons it is so dii-
cult to maintain weight loss. If we can restore
or improve the function of TRPV1 channels
it will have implications not only on weight loss
but also weight maintenance.
In addition to the dampened response
to mechanical stretch there are also
changes in the effect of gastric hormones
on nerves innervating the stomach. As
mentioned before, the gastric hormone ghrelin
reduces the response of gastric nerves to stretch. This
reduction is enhanced in high-fat diet-induced obesity,
further reducing the satiety signal from the stomach.
Perhaps more signiicant is the change in effect of the satiety
hormone leptin, which is secreted by fat cells. Leptin circulates
to the brain, where it controls the long-term regulation of food
intake.
Leptin is also found in the stomach, where it modulates the
activity of nerves in response to mechanical stimulation. Inter-
estingly, the effect of leptin on gastric nerves switches from
appetite suppression in lean conditions to appetite stimulation
in high-fat diet-induced obesity.
The mechanism behind this switch in effect is unknown
and currently under investigation. An understanding of this
switch could have huge implications for the pharmacological
treatment of obesity.
In summary, vagal nerves relay information about food intake
from the gastrointestinal tract to the central nervous system,
where it is processed and initiates feedback on the control of food
intake. It is a highly plastic system that adapts to changes in
energy levels and appropriately signals the requirements for
food intake.
However, this system is susceptible to disruption by condi-
tions such as high-fat diet-induced obesity. Understanding the
mechanisms behind these disruptions in function will reveal
ways to overcome the changes observed in high-fat diet-induced
obesity and establish new peripheral targets for the pharma-
cotherapy of obesity.
Amanda Page is a Senior Research Fellow at The University of Adelaide’s Centre for
Nutrition and Gastrointestinal Disease.MAY 2016|| 23Nerves that respond to stretching of the stomach, and therefore
trigger feelings of satiety, are significantly dampened in cases of
obesity induced by a high-fat diet. Credit: freshidea/adobe