Effects of Images Following Long-term Aerobic Exercise on Brain Activation

In this pilot study, investigators will use functional magnetic resonance imaging (fMRI) to
determine the effects of high calorie visual food cues [i.e. images of foods that are high
in both sugar and fat (HS/HF), such as ice cream] on activation of appetite and reward
pathways in the brain following long-term (6 months) exercise. Obesity rates are high among
US adults with 33.8% of adults having a BMI of 30 or greater (1). The prevailing belief is
that homeostatic systems are in place to monitor energy homeostasis.

With aerobic physical activity, appetite is affected because a theoretically positive
coupling between energy intake and expenditure is thought to occur (2, 3). During exercise
days, short term studies have demonstrated that there are no differences in appetite except
for a transient decrease 15 minutes post exercise after very hard exercise(4). Short term
exercise does not result in appetitive differences (5-7). However in the medium term, there
is a variable (mixed) response (5). Over the long-term it is thought a loose coupling exists
between exercise and appetite response (5).

Our preliminary data strongly support a positive coupling between exercise and appetitive
responses because in previous studies the amount of weight loss that is achieved following
aerobic exercise is less than expected. Specifically, studies by Tim Church have previously
found that hypertensive overweight postmenopausal women did not lose ~2.6 kg but instead 1.4
kg (8). This is a 46% difference between how much weight should be lost due to energy
expended with exercise compared to the actual amount. Another study examined 4 months of
moderate intensity aerobic exercise of 16KKW (9) and again about 2.7 kg of weight loss was
expected but only 1.1 kg was achieved. This suggests a 59% difference. Both studies had very
low dropout rates. Based on the results of the highest dose of exercise in these two
studies, the discrepancy grows with an increase in exercise dose. The participants were
instructed not to change eating habits and physical activity outside of the intervention and
these were not significantly altered. These body weight responses mirror the majority of
aerobic exercise intervention studies. King et al. performed a supervised aerobic exercise
study (10). 58 persons completed 500 kcal/d of exercise induced energy expenditure for 5
d/wk over 12 weeks with a 28% dropout rate. Overall an average of just 3.2 kg of body weight
was lost. Over 50% of persons failed to lose the expected amount and 15% of persons gained
weight (11). Four out of ten studies in a review found exercise did not even result in a
body weight difference between the exercise and control groups(12). This differential
response in energy balance is thought to be driven by increased energy intake. Stubbs et al.
performed a randomized crossover study with 3-7 day exercise treatments. The exercise
treatments were no exercise, then medium exercise (~1.9 MJ/day) and lastly high exercise (~
3.4MJ/day). Energy expenditure increased in the no exercise (9.2 MJ/day), medium exercise
(11.0 MJ/day) and high exercise conditions (12.1 MJ/day), respectively. A statistically
significant increase in energy intake with exercise was found (no exercise 8.9 MJ/day,
medium exercise 9.2 MJ/day, and high exercise 10.0 MJ/d). Thus based on body weight and
these energy intake data from Stubbs et al. investigators feel there is a biological drive
to increase energy intake following exercise. Investigators seek to determine the neural
mechanism of this appetitive response in the proposed grant.

Previously 2 aerobic exercise studies examining for the neuronal response to images have
been performed. Ours are similar and will provide PBRC with pilot data for further
investigations. Evero et al. previously found that reward pathway neuronal cues were reduced
following aerobic exercise (13). Cornier et al. found that chronic exercise alters the
neuronal response to food cues. However this study was confounded due to significant weight
loss which as stated above does not generally happen with aerobic exercise trials. The
results suggested the insula may be particularly important in exercise induced weight loss
and weight loss maintenance (14). This study hopes to examine the neuronal responses to
aerobic exercise without weight loss.

Obesity Women were shown food picture cues of high energy foods. The high energy foods
produced significantly greater activation in the brain reward regions in obese compared to
normal weight control women (15). Differences between groups included ACC, VTA, nucleus
accumbens (NAc), amygdala, ventral pallidum (Vent Pall), Caudate, and Putamen (15).
Postmeal, obese individuals, but not normal weight individuals, increase activation of the
putamen (part of striatum) and amygdala suggesting these regions may play a role in
overeating (16) which is why these regions are incorporated into the current study
hypothesis. These cross-sectional studies are important as previously Murdaugh et. al (17)
found that obese individuals that were not successful at short term weight loss or longer
term weight loss maintenance had greater activation of reward pathway brain regions. While
speculative, artificial sweeteners may reduce cravings by not activating reward pathways
especially in obese persons. This grant will help provide pilot data to further elucidate
this important question.

Inclusion Criteria:

- Male or Female

- 18-65 years old (inclusive)

- Weigh less than 350 lbs

- Body mass index (BMI) between 25-43 kg/m2

- Willing to fast for 10 hours prior to examination

- Right handed

Exclusion Criteria:

- Diagnosis (by self report) of diabetes

- Diagnosis (by self report) of neurological condition

- Current or past alcohol or drug abuse problem

- Smoking

- Have internal metal medical devices including cardiac pacemakers, aortic or cerebral
aneurysm clips, artificial heart valves, ferromagnetic implants, shrapnel, wire
sutures, joint replacements, bone or joint pins/rods/screws/clips, metal plates,
metal fragments in your eye, or non-removable metal jewelry such as rings

- Unable or unwilling to complete the imaging procedures for the duration of the MRI
scan due to claustrophobia or other reason