Lecture 6 Whole Body Energy Balance

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

B/fast Lunch Dinner Sleep Activity Rate energy Intake (kJ/min) Rate energy output (kJ/min) Time of Day (24 hr)

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!!!

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!

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?

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 O 2 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

Basal Metabolic Rate (MJ/day) Fat free mass (kg) Non-obese Obese

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

Indirect Calorimetry Measure rate of O 2 consumption Because energy expenditure linked to the rate of the electron transport chain and the latter involves oxygen consumption Assume that energy released when O 2 is used = 20.2 J/ml (for fat, CHO, protein) –Ratio of O 2 :CO 2 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

Doubly Labelled Water Subject consumes 2 H 2 18 O (D 2 18 O) Like normal H 2 O This reacts with CO 2 produced in fuel oxidation to form H 2 CO 3 All the oxygen atoms in H 2 CO 3 are equivalent, so during the reverse reaction, some oxygen goes into CO 2 and will be lost at the lungs. The rate of 18 O loss could then be used to guage how much CO 2 was produced –And hence the rate of fuel oxidation Since oxygen could also be lost through water excretion, we need the 2 D 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

The Harris Benedict Equation Estimate BMR Women: = ( 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 to get into kJoules.

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 –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 –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.

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

Body Weight (kg) Age (years) 50 percentile leptin So could leptin injections be the ‘cure’ for obesity?

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 Leptin (ng/ml) Body Fat (%)