Oral, gastric and cognitive contributions to satiation

Obesity is one of the world*s major health problems and the number of obese
people in the western society continues to increase. One of the major
contributors to obesity is the obesogenic food environment that is
characterised by large portion sizes of palatable, high energy dense foods that
can be consumed at a fast rate.
The ability of the human body to regulate food intake plays a key role in the
prevention of overconsumption. When food is consumed at a quick rate the in
mouth perception to food (oro-sensory exposure) is limited. Because of that,
some people are not able to regulate food intake causing overconsumption and
ultimately an increase in body weight.
Food intake is controlled by the hypothalamus which is continuously informed
about the metabolic state of the body. The hypothalamus is among which informed
by peripheral signals triggered by oro-sensory exposure, stomach content or
distention conveyed by gastrointestinal peptides. However we do not know which
of these signals plays the most important role in meal termination or feeling
satiated. For example studies have shown that slower eating and longer chewing
lead to higher postprandial satiety hormone responses indicating that
oro-sensory exposure to food plays an important role in meal termination.
However, gastrointestinal *kinetics* function, upon eating, may also play a key
role in the regulation of satiation. For example stomach distention activates
stretch and mechanoreceptors that send satiety signals to the brain. Although
often the meal is terminated before the stretch sensors are activated. Also the
gastric emptying rate especially in high caloric foods sends satiety signals to
the brain . The gastrointestinal peptides involved in appetite regulation are
Ghrelin, CCK, PYY and GLP1. Besides the oro-gastric signals cognitive factors
play an important role in terminating a meal led by the perceived sensory
qualities of a food. Sweet and harder foods are thought to be more filling and
palatability of a food may result in eating beyond metabolic needs.
The separate roles of oral and gastric signals and the cognitive role in intake
regulation are not completely understood. Therefore the primary objective of
this study is to determine whether, oral, or gastric feedback is most important
for meal termination (satiation). As a secondary objective we aim to understand
how cognitive factors modulate the oral and gastric signals and which
gastrointestinal appetite hormones are triggered, and to what extend by the
oral and gastric signals.
We hypothesis that oral feedback together with cognitive factors are most
important for meal termination. In addition, we expect Insulin, Ghrelin, PP,
CCK-8, PYY and GLP-1 endocrine responses to be increased (higher peak and AUC)
when oral signals are limited. However these endocrine responses do not relate
to food intake as this is overruled by cognitive factors (Lack of mouth feel
and hedonic evaluation of food).
Buy understanding the pathways through which food intake is regulated we could
also understand possible roles of alterations of this mechanism in the
pathophysiology of obesity. In addition overweight obese people could
specifically be trained to focus on the products* taste, texture or stomach
feelings to become more aware of the amount eaten within a meal.

The primary objective of this study is to determine whether, oral, or gastric
feedback is most important for meal termination (satiation). As a secondary
objective we aim to understand how cognitive factors modulate the oral and
gastric signals and which gastrointestinal appetite hormones are triggered, and
to what extend by the oral and gastric signals.

The study has a randomized cross-over study design with 4 conditions; all
participants (n=34) receive each treatment and are their own control (within
subject effects). Participants join an information meeting during which they
sign informed consent when willing to participate, after that participants fill
in a questionnaire about the in- and exclusion criteria of the study. If
eligible, participants come to a screening session for anthropometric measures
(height and weight) and to check Hb-value, fasting glucose levels and blood
pressure and suitability of the veins to insert a cannula. If the participant
fulfills the screening criteria he/she joins a training session during which
the study protocol is practiced and a nasogastric tube is inserted to determine
whether the participants feels comfortable with the insertion of the cannula.
When both the participant and researcher agree that insertion of the tube is
comfortable enough to participate in the four test sessions these sessions are
scheduled. The participant participates in 4 test sessions during which the
participants receives one of the four study conditions in a randomized order.

Participants perform 4 test sessions during which the participant receives one
of the following 4 treatments/conditions. During one session participants eat
the test food in a normal fashion (A. 100% oral ingestion load), in another
session participants receive a gastric load of the test food through a
naso-gastric tube (B. 100% gastric load) but are aware of the amount inserted
in the stomach. During the third condition (C. 50% oral, 100% gastric)
participants receive half of the amount to eat normally while the other half is
loaded in the stomach. During the fourth condition participants can eat
normally (same as condition A) however half of the amount ingested is
siphoned/drained from the stomach (D. 100% oral, 50% gastric condition). In
each condition each participant receives a fixed pre-load after the fixed
preload participants indicate by clicking on a go or no go button on a pc
screening whether or not they would like to receive another piece or load until
they are comfortably satiated. Satiation is thus measured through ad libitum
intake.

The intervention is non-therapeutic to the subjects. The risk associated with
participation is small and the burden can be considered as moderate. During
four sessions participants will be incubated with a naso-gastric tube with
subsequent infusion of a gastric load (two conditions) or stomach content will
be drained (one condition) in one condition a naso-gastric tube will be
inserted but no gastric load will be administered. This procedure may cause
complications although these risks are low when done by a nurse. A likely
complication is irritation of the mucous membrane of the nose or irritation of
the throat for some hours after removal of the tube. To prevent the nose and
throat of becoming too irritated at least one rest week between sessions will
be scheduled. Another likely complication is that participants may feel sick/
nauseous because of insertion of the tube. In some cases the nose or throat may
become to irritate which could lead to a nose bleed or mucosa may become
inflammatory. Wrong placement of the tube may happen whereby the tube is places
in the trachea and food enters the trachea which could have severe consequences
such as pneumonia. However to prevent this from happening the nurse will work
according to a protocol. A pH test will be done to determine if the tube lies
within the stomach (pH *5.5). If the outcome of the test is uncertain and the
location of the tube cannot be determined feeding will not start. A study nurse
will insert and remove the nasogastric tube.The nurse will keep a log to
report about the tube placement/removal of each participant.
The risks of inserting a naso-gastric tube and the procedure will be thoroughly
explained to the participants both verbally and in written.
If during the study endocrine concentrations outside the normal range are
detected, subjects will be notified by the research nurse and redirected to a
general practitioner. Permission for this will also be asked in the IC.
Subjects who do not agree with this requisite are excluded from participation
in this study. With this study we would like to determine how cognitive, oral
and gastric factors contribute to satiation. In other words; why do we stop
eating and when. This knowledge may be used to develop products or strategies
that enhance healthy choices and eating behaviour and consequently help prevent
overweight and obesity. In conclusion, we consider the knowledge obtained and
possible implications of this study to outweigh the individual burden.