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

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

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

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  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. Weight Loss Tachycardia Sweating Hypertension Nervousness Symptoms of Hyperthyroidism

  7. UCP-1 generates heat in brown adipocytes by facilitating a proton leak Regulation of Adaptive Thermogenesis 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. Percent 9.3% 10 8.5% 9 7.2% 8 7 5.5% 6 5 4 3 2 1977 1983 1990 1995 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. 60 52 51 51 51 50 50 40 40 32 Percent of schools 26 30 25 20 13 10 6 10 5 0 K 1st 2nd 3rd 4th 5th 6th 7th 8th 9th 10th 11th 12th 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 (n=17) and ob/ob (n=13) increase basal and total VO2 on high-fat diet. • male mc4r-/- mice (n=18) 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 on:Weight 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. Short and Long Term Weight Regulation Counter regulation Weight gain Usual weight Weight loss Counter regulation

  25. 10% gain 10% loss Energy Expenditure Response to Weight Gain and LossLeibel RL, et al. N Engl J Med 1995;332:621-628 110 600 100 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

  26. 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. Men, Ave  370 min / wk Women, Ave  295 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.

  27. V. Pathophysiology A. Cachexia B. Fever/Hypothermia C. Anorexia – Running Anorexia Model D. Obesity Epidemic 1. Epidemiology 2. Therapeutic Approaches

  28. Illness-Induced Cachexia • Appetite Decreases (even in a starved state) • Metabolic Rate Elevated • Increased Wasting of Lean Body Tissues • Diminished Protective Endocrine Response

  29. 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

  30. MC4-R Signaling is Involved in Cachexigenic Signaling

  31. Examples of a experimental models of cachexia Marks et al., Endocrinology 144, 2003

  32. Is BMR Reduced in Obesity? D. Obesity Epidemic 1. Epidemiology 2. Therapeutic Approaches 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?

  33. 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 days…or… about 10 kcal / day = 2 lifesavers or 1 potato chip The Adipostat Does Not Seem to Respond to Slow Weight gain

  34. 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

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