Physical Activity, Appetite and

the Brain
Marc-Andre Cornier, M.D.
Associate Professor of Medicine
Division of Endocrinology, Metabolism and Diabetes
Anschutz Health and Wellness Center
University of Colorado School of Medicine
marc.cornier@ucdenver.edu
Case 1
The patient is a 36 year old overweight woman who
wants help with losing weight. She wanted to get
healthy and lose weight as her New Years
Resolution so joined a fitness center. She went at
least 5 days a week for the past 3 months spending
45-60 minutes doing aerobic exercise with some
resistance training mixed in. While she does feel
better about herself, she is very frustrated because
she has not lost any weight! She has not changed
her diet during this time as she feels that her diet is
pretty healthy. Why havent I lost weight? What else
can I do? she asks in frustration
Case 1
Why hasnt she lost weight?
She has clearly added exercise to her lifestyle which
should be associated with several hundred calories
burned daily.
Either she is less active the remainder of the day or
during her non-exercise days
Or she has compensated by taking in more calories
Or...
Is exercise not a good tool for weight loss?
Does compensation occur?
How are we going to help her?
Case 2
The patient is a 36 year old overweight man who
gained weight after suffering a bad knee injury and
not being able to work out the past 4-6 months like he
used to. He has now been given clearance to start
running again. Three months later he has lost 15
pounds and feels good. He has also tried to eat
more healthy during this time
Case 2
Why did he lose weight with exercise?
Did he just burn more calories than the woman in
case 1?
Did he simply cut his caloric intake as the main
reason for his weight loss?
Does exercise impact his physiologic regulation
of energy balance differently than the woman in
case 1?
Are his behaviors more conducive to dealing with
the environment?
How does he adapt?


The Effects of Physical Activity on
Body Weight
Physical activity in of itself has been shown to
have only modest (<3%) effects on weight loss
on average.
But, physical activity accentuates diet-induced
weight loss.
But, physical activity is important in minimizing
weight gain and regain.
Also, there is significant inter-individual
variability in the response to exercise
interventions.
Variability in Weight Change with an
18-Month Physical Activity Intervention
Jakicic et al Obesity 2011;19:100
Variability in Weight Change with a
6-Month Exercise Intervention of Varying Dose
Church et al PLoS One 2009;4:e4515
Variability in Weight Change with a
6-Month Exercise Intervention
Melanson et al. unpublished
-20
-15
-10
-5
0
5
10
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
Weight Loss (kg)
Less Weight Loss Than Predicted with
an Exercise Intervention
Church et al PLoS One 2009;4:e4515
Potential Adaptation/Compensation
to Exercise
Decreased Energy Expenditure
Resting or Basal Metabolic Rate?
Non-Exercise Activity
Changes in Nutrient Metabolism
fat burn
nutrient absorption
Reduced Food Intake/Appetite
Changes in physiologic appetite signals
Changes in Cognitive/Behavioral signals
Does physical activity or exercise
impact the regulation of food intake,
and if so how?
Acute Effect of Walking on Energy
Intake in Overweight/Obese Women
Unick et al Appetite 2010;55:413
Appetite Responses to Acute
Equivalent Energy Deficits Created
By Exercise or Food Restriction
King et al JCEM 2011;96:1114
Control
Ex-Def
Food-Def
The Effects of Chronic Exercise on Appetite
Martins et al JCEM 2010;95:1609
Control
Ex-Def
Control
Ex-Def
Effects of Exercise on
Energy Intake and Energy Expenditure
Blundell et al Proc Nutr Soc 2003;62:651
Energy Intake Energy Expenditure
days days
No exercise
Medium level of exercise
High level of exercise
Variable Effects of Walking on
Energy Intake
Unick et al Appetite 2010;55:413
Variability in Change in Hunger & Energy Intake
with an 12-Week Exercise Intervention
King et al AJCN 2009;90:921
Variability in Weight Change & Energy Intake
with an 12-Week Exercise Intervention
King et al AJCN 2009;90:921
The Effects of Physical Activity on
Body Weight
Physical
Activity
Energy
Expenditure
Appetite
BW
Energy
Intake
Physical
Activity
Energy
Expenditure
Appetite
BW
Energy
Intake
X
Whats regulating these
differences in appetite and
energy intake?
Energy Homeostasis
Leptin
Adipose Tissue
Intake
Energy
Expenditure
Insulin
Catabolic
Pathways
+
Anabolic
Pathways
Energy homeostasis
Leptin
Adipose Tissue
Intake
Energy
Expenditure
Insulin
Catabolic
Pathways
+
Anabolic
Pathways
Ghrelin
PYY
GLP-1
+
How Does Exercise Impact These Systems?
Leptin
Adipose Tissue
Intake?
Energy
Expenditure?
Insulin
Catabolic
Pathways
+
Anabolic
Pathways
Ghrelin?
PYY?
GLP-1?
+
Non-Physiologic Regulation
of Energy Intake
Internal Inputs
Reward Mechanisms
Cravings
Thinking about food
Restraint
Learned Behaviors
Attention
External Inputs
Environmental Cues
Sight
Smell
Taste
Availability/Portions
Social Context
Time cues
Hypothalamus
Energy Intake
Adiposity Signals
Gut Peptides
Physiologic Non-Physiologic
Metabolites
Gastric Distension
Regulation of Energy Intake
Internal Inputs
External Inputs
Hypothalamus
Energy Intake
Physiologic
Adiposity Signals
Gut Peptides
Metabolites
Gastric Distension
Regulation of Energy Intake
Non-Physiologic
Internal Inputs
External Inputs
Studying Energy Intake Regulation
What Can We Measure in Humans?
Behaviors
Appetite very subjective
Energy Intake how accurate?
In the lab vs free living
Hormones and Metabolites
Only tell you whats happening in the periphery
Can neuroimaging
help us better understand
these adaptations?
What is fMRI?
Subject performs a
cognitive task in blocked
design
Neuronal activity leads to
localized changes in blood flow
Local change in the ratio of oxy-Hb
to deoxy-Hb causes detectable
change in magnetic field
Dukelow et al., 2001
Subject is inserted into 3T magnet,
exposing brain to uniform
magnetic field
Modified from Bushong, 1996
Effects of Acute Exercise on the
Neuronal Response to Visual Food Cues
Evero et al, J Appl Physiol 112:1612-1619, 2012.
60 min of high intensity exercise resulted in acute reductions
in neuronal response to food cues in brain regions important
in food-related reward, motivation and anticipation.
Effects of Acute Exercise on the
Neuronal Response to Visual Food Cues
Crabtree et al, Am J Clin Nutr 99:258-267, 2014.
60 min of high intensity exercise resulted in acute reductions in
neuronal response to food cues in brain regions important in food-
related reward and memory and increased areas of inhibitory control.
Effects of Self-Reported Exercise on the
Neuronal Response to High-Calorie Food
Kilgore et al, NeuroReport 24:962-967, 2013.
Amount of self-reported physical exercise is associated with reduced
neuronal response to food cues in brain regions important in reward
processing, appetite and awareness.
Effects of a 6-Month Exercise
Intervention on the Behavioral and
Neuronal Responses to Food
Methods
Subjects (N=12, 7M/5W):
Age: 18-55 (38.2 9.5 y)
BMI: 27-40 (33.3 4.3 kg/m
2
)
Otherwise healthy nonsmokers
Weight stable, No regular exercise
Design:
Baseline assessments
6-month progressive exercise intervention
Individualized 2500 kcal/wk target; theoretical wt loss of ~6.8 kg
Exercise prescription calculated from baseline VO
2
max test
No attempt to modify energy intake or eating behaviors
Post-intervention assessments
Methods
Assessments:
Body Weight and Composition
Eating Behaviors:
Three Factor Eating Inventory (restraint, disinhibition, hunger)
Food Craving Questionnaires
Appeal and Desire for Foods
Appetite:
Visual Analog Scales for Hunger and Satiety
fMRI:
Neuronal Response to Visual Food Cues
Resting-State Response

Change in Body Weight with a
6-Month Exercise Intervention
99 6 kg
B
o
d
y

W
e
i
g
h
t

(
k
g
)

102 5 kg
*p = 0.09
Cornier et al, Physiol Behav 105:1028-1034, 2012
0
10
20
30
40
50
60
70
80
Restraint Disinhibition Craving Desire Appeal
Baseline
Final
Change in Eating Behaviors with a
6-Month Exercise Intervention
Cornier et al, Physiol Behav 105:1028-1034, 2012
A
r
e
a

U
n
d
e
r

t
h
e

C
u
r
v
e

Change in Appetite with a
6-Month Exercise Intervention
Cornier et al, Physiol Behav 105:1028-1034, 2012
Summary of Eating Behaviors
Despite increased energy expenditure and weight loss
(on average), the exercise intervention did not
significantly impact any of the behavioral measures as
one might predict.
These findings suggest that chronic exercise may
promote weight loss and/or weight maintenance by
attenuating the expected changes in eating behaviors
and therefore not enhancing energy intake.
These responses, though, are still quite variable.
Might this be due to changes in leptin sensitivity in some
and not others? Do some eat more outside of appetite
regulation than others?
Neuronal Response to Food
Cues with Chronic Exercise
Visual Stimuli
Basic or Utilitarian Food Highly Palatable or Hedonic Food
Control Object
The Neuronal Response to
Hedonic Foods at Baseline
Hedonic Foods > Non-Food Objects
Cornier et al, Physiol Behav 105:1028-1034, 2012
Effects of Chronic Exercise on the Neuronal
Response to Hedonic Foods
Baseline > Exercise
Hedonic Foods > Non-Food Objects
Cornier et al, Physiol Behav 105:1028-1034, 2012
Correlation Between Change in Weight and
Change in Insula Response
Cornier et al, Physiol Behav 105:1028-1034, 2012
The Brains Resting-State
Default Network
Tregellas et al, Obesity 2011.
Effects of Exercise on Resting-State
Default Mode and Salience Network
McFadden et al, NeuroReport 24:866-871, 2013.
The greater the
reduction in DMN
activity the greater the
reduction in fat mass
(r=0.72, p=0.01) and
body weight (r=0.59,
p=0.06)
Summary of Neuronal Responses
to Chronic Exercise
Chronic exercise is associated with a reduction in the
neuronal response to food, primarily in brain regions
known to be important in food intake regulation, as well
as in the default mode network.
Is this a normalization of response?
There was a significant relationship between the brain
changes and change in weight. In fact, effects were
driven by those who lost weight as compared to those
who did not.
Success of physical activity may be by impacting the
motivation, reward, and attention for food .
Conclusions
Physical activity is associated with less effects on appetite
and energy intake than would be expected for the degree
of negative energy balance.
The effects of physical activity on energy intake are quite
variable.
The effects of physical activity on the neuronal response to
food cues is also variable and appears to predict changes
in body weight.
Better understanding these mechanisms will hopefully
help us to:
1. better predict the response to physical activity interventions
2. develop new tools/interventions for successful weight loss
and/or weight gain prevention
Future Directions
Two follow up studies under way:
1. Examining the effects of exercise on appetite regulation after
weight loss, i.e. during weight-loss maintenance
2. Examining the effects of exercise as compared to diet on appetite
regulation during weight loss
Areas of interest:
1. Effects of different intensity of exercise
2. Effects of resistance as compared to aerobic exercise
3. Time of day of exercise
4. Effects of reducing inactivity on appetite regulation
Acknowledgements
Imaging:
Jason Tregellas
Kristina McFadden
Jamie Bechtell
Deb Singel
Exercise:
Ed Melanson
University of Colorado SOM:
Brain Imaging Center
CTRC
CNRU
AHWC
NIH/NIDDK
American Diabetes Assoc
Thank You For Your Attention!






Bon Apptit!