Starving to slim

Body mass index (BMI) = weight in kg / (height in metres squared).
= 90 / (1.52 x 1.52) = 38.9

You would classify her as being obese

If BMI = weight / height-squared then weight = BMI x height-squared = 25 x (1.52 x 1.52) = 57 kg

If her target weight is 57 kg then she has to lose 33 kg.

The energy yield of adipose tissue can be calculated from the fact that it contains 80% triacylglycerol (at 37 kJ /gram) and 5% protein (at 17 kJ /gram). Therefore 100 g of adipose tissue yields:

• from triacylglycerol: 80 x 37 = 2960 kJ
• from protein: 5 x 17 = 85 kJ
• total = 3045 kJ = 3.045 MJ / 100 g adipose tissue = 30 MJ / kg adipose tissue (rounding off)

33 kg adipose tissue yields 33 x 30 MJ = 990 MJ
she requires 10 MJ / day, so it will take her 990 / 10 = 99 days to lose 33 kg.

On the basis of these calculations she can lose 33 / 99 = 0.33 kg /day, or a maximum theoretically possible 2.3 kg / week by starving completely.

You need to think about the structure of glycogen and compare the storage of carbohydrate (as glycogen) and triacylglycerol (in adipose tissue).

Glycogen is a branched polymer of glucose linked a(1-4), with branch points provided by a(1-6) links:

This highly branched structure of glycogen (consisting of very hydrophilic glucose monomers) traps a large amount of water. As glycogen reserves in liver and muscle are depleted in the early stages of fasting, there will be a considerable loss of water, and hence a loss of more weight than can be accounted for by the utilisation of adipose tissue reserves.

By contrast, triacylglycerol is stored in lipid droplets in adipose tissue cells, and 80% of the mass of adipocytes is triacylglycerol, with only a small amount of water in the cytosol.

No - The brain is largely reliant on a source of glucose, and red blood cells entirely so - neither can metabolise fatty acids. This means that there will have to be considerable catabolism of muscle (anfd other tissue) protein to provide amino acids for synthesis of glucose (gluconeogenesis). For reasons that wil become apparent in a later exercise, fatty acids can never be used for gluconeogenesis. The glycerol from breakdown of triacylglycerol can be used for synthesis of glucose, but not nearly enough to meet the needs of the brain and red blood cells.

Although the triacylglycerol in her adipose tissue would be more than enough to meet her energy needs, the loss of protein to provide a substrate for gluconeogenesis means that she would be unlikely to survive starvation for as long as 99 days - some protein can be lost from tissues without causing any significant harm, but eventually there would be significant losses of essential tissue proteins, and she would die.

Also, she would need a source of vitamins and minerals to replace those lost in metabolic turnover - with no dietary source, she would start to show signs of vitamin B1 deficiency within a week or so of starvation.

If she consumes 15.8 litres of oxygen per hour, and 1 litre is equivalent to 20 kJ,
then her resting metabolic rate is 20 x 15.8 = 316 kJ per hour
= 316 x 24 = 7580 kJ / 24 hours = 7.58 MJ /24 hours

• Even at rest there is some work being performed by muscles - to maintain circulation and breathing and generally maintain muscle tone.
• Sodium, potassium and calcium ions are transported across cell membranes and between intracellular compartments by active transport, which is energy requiring.
• There is continual breakdown of tissue proteins and replacement synthesis - both processes are energy requiring.
• Many enzyme catalysed reactions are endothermic and require an input of energy.

Approximate percentage of resting energy expenditure in different processes:

The ketone bodies are two 4-carbon compounds, acetoacetate and hydroxybutyrate, which are formed in the liver from the products of fatty acid oxidation. Acetone is also formed, by non-enzymic breakdown of acetoacetate. However, it is poorly metabolised, and is lost on the breath and in the urine.

(Note that although acetoacetate and acetone are chemically ketones, hydroxybutyrate is not. All three compounds are grouped together as "ketone bodies" because of their metabolic relationship)

Much of the acetoacetate formed in the liver is reduced to hydroxybutyrate in order to prevent the loss of metabolic fuel that occurs when acetone is formed.

In fasting and starvation the main problem is to maintain a supply of glucose for the brain (which is largely reliant on glucose) and the red blood cells (which are wholly reliant on glucose). Although muscle can use fatty acids as a fuel, in fasting and starvation it is not capable of oxidising enough fatty acid to meet all of its energy needs. By contrast, the liver can oxidise more fatty acids than it needs, and synthesises ketone bodies to export to other tissues as a water-soluble metabolic fuel.

Initially her plasma glucose concentration will be maintained by breakdown of liver reserves of glycogen (and indirectly also form muscle glycogen). These will be depleted within 24 hours or so, and then she will start to use amino acids arising from the breakdown of tissue protein to synthesise glucose (the process of gluconeogenesis).

On the days when she has a blood sample taken, EW also collects her urine for 24 hours. Her excretion of urea is measured:

Urea is the end-product of metabolism of the amino groups of amino acids. The urinary excretion of urea therefore reflects the amount of amino acids being metabolised, with their carbon skeletons being used (mainly) for gluconeogenesis.

By 2 weeks her plasma concentration of ketone bodies has risen sufficiently for the brain to be able to oxidise them to meet a significant proportion of its energy needs (perhaps as much as 20 - 40%).This means that there is less need for gluconeogenesis from amino acids. Plasma glucose can fall somewhat (because the brain is using ketone bodies to replace part of the glucose it was using) and there will be less breakdown of tissue protein. Therefore there will be less urea excreted.

It would not be desirable for a patient who is about to undergo surgery to lose too much tissue protein - as you will see in a later exercise, one of the effects of surgery is to stimulate a considerable loss of tissue protein anyway. After a series of studies that gave results like those shown here, a novel method of helping obese patients to lose weight before surgery was developed - from the beginning of the starvation they were given an intravenous infusion of hydroxybutyrate, so as to mimic the effect of more prolonged starvation, and provide a high enough plasma concentration to allow the brain to meet part of its energy needs from ketone bodies. This resulted in lower excretion of urea and less loss of tissue porte in, because of the reduced need for gluconeogenesis.

Key points from this exercise:

• The energy yield of adipose tissue can be calculated from the fact that it contains 80% triacylglycerol (at 37 kJ /gram) and 5% protein (at 17 kJ /gram). Therefore 100 g of adipose tissue yields:
• from triacylglycerol: 80 x 37 = 2960 kJ,
• from protein: 5 x 17 = 85 kJ,
• total = 3045 kJ = 3.045 MJ / 100 g adipose tissue = 30 MJ / kg adipose tissue (rounding off).
• Total starvation, and assuming energy expenditure of 10 MJ /day, would give a maximum theoretically possible weight loss of 2.3 kg / week.
• In the first few days of severe energy restriction there is a considerable loss of water trapped in glycogen reserves that are being depleted, so there may well be a greater loss of weight than that calculated from adipose tissue.
• Not all of the weight lost will be adipose tissue. The brain is largely dependent on a supply of glucose, and red blood cells completely so. There will be a loss of muscle tissue to provide amino acids for synthesis of glucose (gluconeogenesis).
• Fatty acids can never be a source of substrates for gluconeogenesis (although the glycerol from triacylglycerol is used for gluconeogenesis).
• Even if adipose tissue reserves are adequate to meet energy needs for a prolonged period, it is unlikely that anyone would survive starvation for more than about 40 days, because of the loss of protein for gluconeogenesis, and the need for vitamins and minerals to replace losses.
• It is possible to measure metabolic rate by measuring oxygen consumption. To first approximation each litre of oxygen consumed is equivalent to 20 kJ, regardless of the fuel being oxidised.
• Resting metabolic rate is the energy needed:
• to maintain circulation and breathing and generally maintain muscle tone.
• for active transport of ions across cell membranes and between intracellular compartments
• to maintain protein turnover - there is continual breakdown of tissue proteins and replacement synthesis; both processes are energy requiring.
• to provide an input of energy for endothermic enzyme catalysed reactions.
• Plasma glucose falls somewhat in the fasting state, but then remains more or less constant into prolonged starvation.
• Plasma free (non-esterified) fatty acids rise somewhat in the fasting state, but then remains more or less constant into prolonged starvation.
• Plasma ketone bodies rise steadily with increasing time of starvation.
• The ketone bodies are acetoacetate, hydroxybutyrate and acetone. Acetoacetate and hydroxybutyrate are synthesised in the liver and provide an alternative fuel for muscle, which cannot meet its energy needs from fatty acids alone, and in advanced starvation become a significant fuel for the brain as well.
• Acetone is formed by non-enzymic decarboxylation of acetoacetate, and is poorly metabolised. Much acetoacetate is reduced to hydroxybutyrate in the liver before release in to the bloodstream
• Urea is the end-product of metabolism of the amino groups of amino acids. The urinary excretion of urea therefore reflects the amount of amino acids being metabolised, with their carbon skeletons being used in starvation (mainly) for gluconeogenesis.