Energy Expenditure Roger D. Cone, Ph.D. MPB 333

1
Energy ExpenditureRoger D. Cone, Ph.D.MPB 333
2
I. Energy Expenditure in the Context of Energy
HomeostasisII. Forms of Energy Expenditure A.
Resting Metabolic Rate 1. Homeotherms and
adaptive thermogenesis a. non-shivering
thermogenesis b. shivering B. Voluntary and
Involuntary Physical Activity 1. Exercise 2.
NEAT C. Diet-Induced ThermogenesisIII.
Techniques for Measuring Energy ExpenditureIV.
Regulation of Energy ExpenditureV.
Pathophysiology A. Cachexia B.
Fever/Hypothermia C. Anorexia Running Anorexia
Model D. Obesity Epidemic 1.
Epidemiology 2. Therapeutic Approaches
3
II. Forms of Energy Expenditure
Basal Metabolism 60 Thermic Effect of Food
8-10 Physical Activity 30-32
4

RMR is primarily regulated by the thyroid axis
and autonomic tone
Leptin regulates the thyroid axis to maintain
energy homeostasis
5
Anatomy of the Thyroid Axis
Leptin regulates the thyroid axis to maintain
energy homeostasis
6
Symptoms of Hyperthyroidism
Weight Loss Tachycardia Sweating Hypertension
Nervousness
7
Regulation of Adaptive Thermogenesis
UCP-1 generates heat in brown adipocytes by
facilitating a proton leak
Thyroid Hormone and Sympathetic Tone Regulate
UCP-1 Activity
8
Adaptive Thermogenesis Acute Response to
Cold
9
Does Inherent Variability in NEAT Determine
Obesity?
10
Creating a NEAT Intensive Environment
11
B. Voluntary and Involuntary Physical
Activity 1. Exercise 2. NEAT
Few people exercise regularly, NEAT varies by up
to 2000kcal/day, therefore NEAT is very important!
12
Percentage of All Trips Made From Home by
Walking, 1977 - 1995
1
0
Source National Personal Transportation Survey,
1995
13
Percentage of U.S. High School Students Who
Attended Physical Education Classes Daily, 1991 -
1999
Source CDC, National Youth Risk Behavior Survey
14
School Health Policies and Programs Study 2000
Physical Education Requirements by Grade
15
Average Daily Time Children Spent Using Media, by
Medium and Age, 1999
N 3,155 children, ages 2-18 (nationally
representative) margin of error 3-5 Source
Kaiser Family Foundation. Kids and Media at the
New Millenium, 1999
16
Televisions in the Home

• Nearly a third (32) of children live in homes
  with 4 or more TVs
• 53 of all children, ages 2-18, have a TV in
  their bedroom

N 3,155 children, ages 2-18 (nationally
representative) margin of error 3-5 Source
Kaiser Family Foundation. Kids and Media at the
New Millenium, 1999
17
C. Diet-Induced Thermogenesis (DIT)or Thermic
Effect of FoodThe energy expended as a function
of differential food consumed, controlling for
RMR and activityProbably composed of actual
energy required for digestion plus a regulatory
response to caloric intake
18
Defective Diet-induced Thermogenesis in the
MC4-R -/-

• ob/ob mice have significantly lower VO2 than
  wildtype and mc4r-/- mice.
• male wt (n17) and ob/ob (n13) increase basal
  and total VO2 on high-fat diet.
• male mc4r-/- mice (n18) do not show significant
  response to change in diet.

19
MC4-R is Required for High Fat Diet Induced
Upregulation of UCP-1
20
III. Techniques for Measuring Energy
Expenditure1. In indirect calorimetry, oxygen
consumption and/orcarbon dioxide production is
measured and convertedto energy expenditure
using formulae2. In direct calorimetry, the
rate of heat loss from thesubject to the
calorimeter is measured.3. A number of
non-calorimetric techniques have beenused to
predict the energy expenditure by
extrapolationfrom physiological measurements and
observations.
21
Comparing Energy Expenditure in Different Animals
is Highly Problematic
22
Comparing Metabolic Rates in Different Animals is
Highly ProblematicHow to normalize?Weight is
misleading because lean mass is more
metabolically active than fat massEstimates are
based onWeight 0.66Weight 0.75Determination
of lean massBest Method relationship of EE to
fat free mass within group, then comparison of
groups
23
IV. Regulation of Energy Expenditure
24
(No Transcript)
25
Short and Long Term Weight Regulation
Counter regulation
Weight gain
Usual weight
Weight loss
Counter regulation
26
Energy Expenditure Response to Weight Gain and
LossLeibel RL, et al. N Engl J Med
1995332621-628
110
600
100
Initial Weight
of Initial Weight
400
90
80
Mean (/- SD) Observed minus Predicted Total
Energy Expenditure (Kcal/day)
200
10 loss
70
Time ?
0
Initial Weight
10 gain
200
400
27
Effect of Exercise on Body Weight in Overweight
Men and WomenIrwin, et al. Obes Res.
15(6)1496-1512, 2007.

• Target of 60-minutes moderate-intensity,
  aerobic exercise 6-days a week x 1 yr. Verified
  by increased V02 max.

Women, Ave ? 295 min / wk
Men, Ave ? 370 min / wk
-1.9 kg FM 0.5 kg FFM
-3 kg FM 1.2 kg FFM
NO difference in food intake between exercisers
and controls after 12 months.
28
V. Pathophysiology A. Cachexia B.
Fever/Hypothermia C. Anorexia Running Anorexia
Model D. Obesity Epidemic 1.
Epidemiology 2. Therapeutic Approaches
29
Illness-Induced Cachexia

• Appetite Decreases (even in a starved state)
• Metabolic Rate Elevated
• Increased Wasting of Lean Body Tissues
• Diminished Protective Endocrine Response

30
Cachexia in Disease

• Cancer
• Renal Failure - 26,000 deaths/yr, 87,534 new
  cases/yr, 245, 910 on dialysis, current cost of
  treatment 16.74b (1998).
• HIV Infection
• Tuberculosis
• Cystic Fibrosis
• Failure to Thrive - 5 of peds. admissions
• Cong. Heart Failure - 16 incidence
• COPD - 50 incidence
• Anorexia Nervosa -1 of young women
• Anorexia of Aging - 22 of 70yr olds, up to 60
  of hospitalized elderly

31
MC4-R Signaling is Involved in Cachexigenic
Signaling
32
Examples of a experimental models of cachexia
Marks et al., Endocrinology 144, 2003
33
D. Obesity Epidemic 1. Epidemiology 2.
Therapeutic Approaches
Is BMR Reduced in Obesity?
After tens of thousands of measurements, it is a
universal observation that BMR is raised not
suppressed in obese people because of the fact
that they have a greater lean body mass (LBM)
than their lean counterparts
Does Reduced BMR Cause Obesity? Do Differences
in TEF Cause Obesity?
34
Could we even measure them accurately enough?
50 year old male 200 lb.
20 year old male 170 lb.
1 lb. per year 3500 kcal / 365 daysor about
10 kcal / day 2 lifesavers or 1 potato chip
The Adipostat Does Not Seem to Respond to Slow
Weight gain
35
D. Obesity Epidemic 1. Epidemiology 2.
Therapeutic Approaches
b3 adrenergic agonists to activate
fat Non-cardiac acting thyroid hormone
analogues
but. Any compounds that increase
energy expenditure may increase heart rate as the
body requires additional oxygen