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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
Lunch
Rate energy
Intake (kJ/min)
150
Dinner
B/fast
100
50
0
Rate energy
output (kJ/min)
30
Activity
20
Sleep
10
0
0
4
8 12 16 20
Time of Day (24 hr)
24
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 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
Non-obese
Basal Metabolic Rate (MJ/day)
10
Obese
9
8
7
6
5
4
35
50
60
Fat free mass (kg)
70
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 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
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
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.
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.
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
120
leptin
Body Weight (kg)
100
80
60
40
50 percentile
20
0
0
2
4
6
Age (years)
•So could leptin injections be the ‘cure’ for obesity?
8
10
No!
• Obese people have higher blood
[leptin]
Leptin (ng/ml)
– More and bigger WAT cells
120
– So extra leptin does not help
– Indeed, they may be leptinresistant
– 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
100
80
60
40
20
0
0
10
20 30 40 50 60 70
Body Fat (%)