Lecture 6

1. Lecture 6 Energy Stores and 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! • See Frayn, fig 1.2 • Like the discordance in petrol intake into a car • On a daily basis, energy intake does not match energy expenditure • Excess in energy consumed over energy expenditure will be stored as fuel reserves • Despite this, weight (fuel reserves) stay remarkably constant over time

3. Fuel Stores • Fat • Three fatty acids esterified to glycerol • Hydrophobic • Stored in absence of water • 37 kJ/g • Very efficient • Stored in white adipose tissue (WAT) • Know the properties of WAT • What adipocytes look like • Where fat cells are located • How they are considered to be endocrine (hormone releasing) • We store about 10-15 kg fat (females > males) • Carbohydrate • Stored as glycogen • Branched polymer of glucose, formed on the protein glycogenin • Hydrophilic • All the –OH groups on glycogen make it very water-attracting and it is associate with lots of water • 6 kJ/g ‘wet’ – NB. Textbooks say that ‘dry’ carbs are 16 kJ/g but remember, in the cell, it is stored in association with water • Stored mainly in Liver (100 g) and muscle (250 g)

4. Why Fat? • Useful to compare the size of the stores • Cup of flour vs 20 litres of cooking oil  • Seems strange that we store nearly all our energy as fat • Brain has obligatory requirement for glucose • We can’t convert fatty acids into glucose (or any carbohydrate!) • Also, muscle glycogen is not available to rest of the body • Only liver glycogen can be released for use by other tissues. • Note about Protein • Not really a stored fuel • We don’t have a specific protein that represents a store of amino acids • Protein is broken down under extreme conditions, but it is expensive to make so it is not suited as a fuel store

5. Intake and Expenditure • Weight (fuel stores) are kept relatively constant • Even though intake and expenditure are highly mistmatched on a day-to-day basis • 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 • 2 g fat per day • 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 • So what are the key components and regulators of intake and expenditure?

6. Expenditure • Three main components (see Frayn Ch 11) • 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?

7. Measuring EE • Indirect calorimetry • Measuring oxygen consumption • Because energy expenditure linked to the rate of the electron transport chain and the latter involves oxygen consumption • Energetic value of oxygen consumption always 20 J/ml regardless of fuel used • Inconvenient and ‘short-term’ • Could use empirical equations • Harris-Benedict • Doubly labelled water • Measure of carbon dioxide production

8. The Harris Benedict Equation Estimate BMR  • Women: • BMR = 655 + ( 9.6 x weight in kilos ) + ( 1.8 x height in cm ) - ( 4.7 x age in years ) • Men: • BMR = 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. 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 or 2x training) :  = BMR x 1.9 Note how the activity doesn't make as much difference as you might expect. See also Frayn Table 8.4 for a list of how various activities increase metabolic rate.

9. 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 (see Frayn Fig 11.5) • Inded the extra weight makes whole body metabolic rate higher • Factors that could potentially change BMR • 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