Lecture 6

1. Lecture 6 Whole Body Energy Balance

2. Intake and Expenditure • Fuel oxidation rate is beautifully matched to ATP demand • Well coupled at the molecular level • But fuel intake is totally mismatched from ATP demand • Ie, we don’t eat at the same time as we consume energy! • On a daily basis, energy intake does not match energy expenditure • Excess in energy consumed over energy expenditure will be stored as fuel reserves • Mainly fat! • Despite this, weight (fuel reserves) stay remarkably constant over time

3. Lunch 150 Dinner B/fast 100 Rate energy Intake (kJ/min) 50 0 30 Activity 20 Rate energy output (kJ/min) Sleep 10 0 0 4 8 12 16 20 24 Time of Day (24 hr)

4. Intake and Expenditure • We seem to have a ‘set point’ • Over months the two sides are VERY finely matched • We are good at ‘defending’ our weight • Weight normally regulated to within about 1 kg/year • A 1 kg rise would represent an imbalance of about 30 MJ per year • Ie, 70 kJ per day • Equivalent to a couple of ml of fat • Or 5 g carbohydrate (a teaspoon of sugar!) • These are imperceptible amounts in dietary analysis • <1% of daily energy intake • Over that year we would have consumed about 4000 MJ • Conversely, putting on weight requires SOME EFFORT!!!

5. Weight Gain Takes Effort! • BMI = mass (kg) divided by the height (m) squared • eg, 83/1.8 x 1.8 = 25.3 • “Normal” 20-25… Overweight 25-30… Obese >30 • A person with BMI of 22 needs to gain 25 kg to get to a BMI of 30 • e.g., a 1.8 m tall person going from 72 kg to 96 kg • Of that, about 19 kg is pure fat and 6 kg is ‘lean’ mass • Fat is 38 MJ/kg, lean is 4.8 MJ/kg • So this extra weight represents an excess of 750 MJ • Would need 2 MJ/day EXTRA to do it all in a year • A person normally consuming 8 MJ/day would need to eat 25% extra EVERY DAY for a whole year • So this sort of weight gain generally takes some time!! • More like 10 years!

6. Energy Expenditure • Three main components • Basal metabolic rate (BMR) – 60% • Resting metabolic rate (RMR) • Physical activity - 30% • Voluntary and Non-exercise activity thermogenesis (NEAT) • Diet-induced thermogenesis – 10% • Thermic effect of food • Obviously the contributions will vary in individuals • We can do something about physical acitvity but • Can we do anything about BMR… • Does BMR vary between individuals? • How do we measure energy expenditure?

7. BMR • BMR is almost totally dictated by LEAN BODY MASS • Ie, the mass of metabolically active tissue • Muscle metabolically active because it is continually pumping ions, even when it is ‘still’ • Adipose tissue is relatively inactive • So plots of metabolic rates vs fat free mass (FFM) are linear • Slope is 4 ml O2 consumed per min per kg FFM (ie, about 100 kJ/day/kg FFM) • Overweight people do not have lower BMRs • Indeed the extra weight makes whole body metabolic rate higher • Higher fat mass is accompanied by higher fat free mass • But metabolic rate vs actual mass not linear at high weights because fat is not as metabolically active

8. Non-obese 10 Obese 9 8 Basal Metabolic Rate (MJ/day) 7 6 5 4 35 50 60 70 Fat free mass (kg)

9. Changing BMR • Metabolic INEFFICIENCIES • Uncoupling proteins • Brown adipose tissue UCP-1, but also maybe UCP-2 and UCP-3 in muscle • More lean body mass • Substrate cycles (futile cycles) • Fuel synthesis then breakdown • Eg, make protein from amino acids consuming ATP, then dismantle the protein (with no gain of ATP) • Leaky membranes • Thyroid hormone • T3 strongly affects metabolic rate • Lack of thyroid hormone reduces BMR • But how? • We know it’s transcriptional but exactly which genes change and how this then changes metabolic rate is not known • Leaky membranes, inefficiencies of NADH transport

10. Indirect Calorimetry • Measure rate of O2 consumption • Because energy expenditure linked to the rate of the electron transport chain and the latter involves oxygen consumption • Assume that energy released when O2 is used = 20.2 J/ml (for fat, CHO, protein) • Ratio of O2:CO2 gives an indication of which type of fuel is burning: • The respiratory quotient • RQ for carbs: 1 • RQ for fat: ~0.7 • Can also tell us if someone is making fat • RQ > 1 • Inconvenient • Not appropriate for ‘free living’ • Can be done during exercise

11. Doubly Labelled Water • Subject consumes 2H218O (D218O) • Like normal H2O This reacts with CO2 produced in fuel oxidation to form H2CO3 • All the oxygen atoms in H2CO3 are equivalent, so during the reverse reaction, some oxygen goes into CO2 and will be lost at the lungs. • The rate of 18O loss could then be used to guage how much CO2 was produced • And hence the rate of fuel oxidation • Since oxygen could also be lost through water excretion, we need the 2D to indicate depletion through excretion, sweating, etc • The difference indicates the true rate of carbon dioxide production. • Very good for long term assessment • But expensive and needs specialised equipment (mass spectrometer!) • Not a measure of BMR

12. The Harris Benedict Equation Estimate BMR  • Women: = 655 + ( 9.6 x weight in kilos ) + ( 1.8 x height in cm ) - ( 4.7 x age in years ) • Men: = 66 + ( 13.7 x weight in kilos ) + ( 5 x height in cm ) - ( 6.8 x age in years ) The only factor omitted by the Harris Benedict Equation is lean body mass. So it is quite accurate in all but the very muscular (where it will under-estimate BMR) and the very fat (will over-estimate BMR) Multiply by 4.184 to get into kJoules.

13. Daily Energy Expenditure • Multiply BMR by the appropriate activity factor: • Sedentary (little or no exercise) : = BMR x 1.2 • Lightly active (light exercise/sports 1-3 days/week) :  = BMR x 1.375 • Moderatetely active (moderate exercise/sports 3-5 days/week) :  = BMR x 1.55 • Very active (hard exercise/sports 6-7 days a week) :  = BMR x 1.725 • Extra active (very hard exercise/sports & physical job :  = BMR x 1.9 Note how the activity doesn't make as much difference as you might expect.

14. Regulation of Food Intake • Controlled by many hormones and neuropeptides • In animals… but in humans more by ‘norm’ behaviour • Leptin • The ‘Adipostat’ or ‘Lipostat’ • Communicates size of fat stores to the brain • Secretion of leptin is proportion to the amount of fat stored in white adipose tissue • Leptin binding to receptors in the hypothalamus elicits satiety • Mice without leptin are hyperphagic, i.e. eat without control • when leptin is injected to these mice: •  food intake •  energy expenditure in brown adipose tissue • People without leptin are hyperphagic • ..and they respond to leptin injections

15. 120 leptin 100 80 Body Weight (kg) 60 40 50 percentile 20 0 2 4 6 8 10 0 Age (years) • So could leptin injections be the ‘cure’ for obesity?

16. No! • Obese people have higher blood [leptin] • More and bigger WAT cells • So extra leptin does not help • Indeed, they may be leptin-resistant • Also humans have a small amount of brown adipose tissue (ie, can’t respond to the leptin by increasing EE) • A lack of leptin may tells us to start eating, rather than a excess of leptin telling us to stop eating 120 100 80 Leptin (ng/ml) 60 40 20 0 0 10 20 30 40 50 60 70 Body Fat (%)