marc cornier, m.d.,: physical activity, appetite, and the brain

8/12/2019 Marc Cornier, M.D.,: Physical Activity, Appetite, and the Brain

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Physical Activity, Appetite and

the Brain

Marc-Andre Cornier, M.D.Associate Professor of Medicine

Division of Endocrinology, Metabolism and DiabetesAnschutz Health and Wellness Center

University of Colorado School of Medicine

[email protected]


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Case 1

The patient is a 36 year old overweight woman whowants 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 ispretty healthy. Why havent I lost weight? What else

can I do? she asks in frustration


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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?


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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 15pounds and feels good. He has also tried to eat

more healthy during this time


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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 withthe environment?

How does he adapt?


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The Effects of Physical Activity on

Body Weight

Physical activity in of itself has been shown to

have only modest (


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Variability in Weight Change with an

18-Month Physical Activity Intervention

Jakicic et al Obesity2011;19:100


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Variability in Weight Change with a

6-Month Exercise Intervention of Varying Dose

Church et al PLoS One2009;4:e4515


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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)


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Less Weight Loss Than Predicted with

an Exercise Intervention

Church et al PLoS One2009;4:e4515


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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


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Does physical activity or exerciseimpact the regulation of food intake,

and if so how?


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Acute Effect of Walking on Energy

Intake in Overweight/Obese Women

Unick et al Appetite2010;55:413


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Appetite Responses to Acute

Equivalent Energy Deficits Created

By Exercise or Food Restriction

King et al JCEM 2011;96:1114

Control

Ex-DefFood-Def


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The Effects of Chronic Exercise on Appetite

Martins et al JCEM 2010;95:1609

Control

Ex-Def

Control

Ex-Def


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Effects of Exercise on

Energy Intake and Energy Expenditure

Blundell et al Proc Nutr Soc2003;62:651

Energy Intake Energy Expenditure

days days

No exercise

Medium level of exercise

High level of exercise


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Variable Effects of Walking on

Energy Intake

Unick et al Appetite2010;55:413


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Variability in Change in Hunger & Energy Intake

with an 12-Week Exercise Intervention

King et al AJCN 2009;90:921


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Variability in Weight Change & Energy Intake

with an 12-Week Exercise Intervention

King et al AJCN 2009;90:921


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The Effects of Physical Activity on

Body Weight

Physical

Activity

Energy

Expenditure Appetite

BW

Energy

Intake

Physical

Activity

Energy

Expenditure

Appetite

BW

Energy

IntakeX


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Whats regulating thesedifferences in appetite and

energy intake?


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Energy Homeostasis

Leptin

Adipose TissueIntakeEnergy

Expenditure

Insulin

Catabolic

Pathways

+

Anabolic

Pathways


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Energy homeostasis

Leptin

Adipose TissueIntakeEnergy

Expenditure

Insulin

Catabolic

Pathways

+

Anabolic

Pathways

GhrelinPYY

GLP-1

+


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How Does Exercise Impact These Systems?

Leptin

Adipose TissueIntake?Energy

Expenditure?

Insulin

Catabolic

Pathways

+

Anabolic

Pathways

Ghrelin?PYY?

GLP-1?

+


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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


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Hypothalamus

Energy Intake

Adiposity Signals

Gut Peptides

Physiologic Non-Physiologic

Metabolites

Gastric Distension

Regulation of Energy Intake

Internal Inputs

External Inputs


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Hypothalamus

Energy Intake

Physiologic

Adiposity Signals

Gut Peptides

Metabolites

Gastric Distension

Regulation of Energy Intake

Non-Physiologic

Internal Inputs

External Inputs


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Studying Energy Intake RegulationWhat Can We Measure in Humans?

Behaviors

Appetitevery subjective

Energy Intakehow accurate? In the lab vs free living

Hormones and Metabolites

Only tell you whats happening in the periphery


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Can neuroimaginghelp us better understand

these adaptations?


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What is fMRI?

Subject performs acognitive task in blocked

design

Neuronal activity leads to

localized changes in blood flowLocal 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


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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.

ff f


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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.

Eff f S lf R d E i h


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Effects of Self-Reported Exercise on the

Neuronal Response to High-Calorie Food

Kilgore et al, NeuroReport24:962-967, 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.


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Effects of a 6-Month Exercise

Intervention on the Behavioral and

Neuronal Responses to Food


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Methods

Subjects (N=12, 7M/5W): Age: 18-55 (38.2 9.5 y)

BMI: 27-40 (33.3 4.3 kg/m2)

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 VO2max test

No attempt to modify energy intake or eating behaviors

Post-intervention assessments


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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

Ch i B d W i ht ith


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Change in Body Weight with a


99 6 kg

BodyWeigh

t(kg)

102 5 kg

*p = 0.09

Cornier et al, Physiol Behav 105:1028-1034, 2012

Ch i E ti B h i ith


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0

10

20

30

40

50

60

70

80

Restraint Disinhibition Craving Desire Appeal

Baseline

Final

Change in Eating Behaviors with a



Ch i A tit ith


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AreaUnderthe

Curve

Change in Appetite with a




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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 maypromote 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?


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Neuronal Response to FoodCues with Chronic Exercise


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Visual Stimuli

Basic or Utilitarian Food Highly Palatable or Hedonic Food

Control Object

The Neuronal Response to


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The Neuronal Response to

Hedonic Foods at Baseline

Hedonic Foods > Non-Food Objects


Effects of Chronic Exercise on the Neuronal


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Effects of Chronic Exercise on the Neuronal

Response to Hedonic Foods

Baseline > Exercise

Hedonic Foods > Non-Food Objects


Correlation Between Change in Weight and


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Correlation Between Change in Weight and

Change in Insula Response


The Brains Resting State


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The Brains Resting-State

Default Network

Tregellas et al, Obesity2011.

Effects of Exercise on Resting State


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Effects of Exercise on Resting-State

Default Mode and Salience Network

McFadden et al, NeuroReport24:866-871, 2013.

The greater the

reduction in DMNactivity 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


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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 .


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Conclusions

Physical activity is associated with less effects on appetite

and energy intake than would be expected for the degreeof negative energy balance.

The effects of physical activity on energy intake are quite

variable.

The effects of physical activity on the neuronal response tofood 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


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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


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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


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Thank You For Your Attention!

Bon Apptit!

marc cornier, m.d.,: physical activity, appetite, and the brain

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