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obesity is a medical problem from the start, but how to distinguish it from benign, non-progressive plumpness has still to be resolved. Even the criteria for defining obesity in children are unclear. Though weight and height charts still have an important role to play in monitoring children’s development, the BMI is less predictive of future events in them than in adults. Fat – or adipose tissue, to give it its technical name – constitutes a higher proportion of a woman’s bodyweight than a man’s. It is only when fat deposits become abnormally large – which can be difficult to determine, machines that are said to do so notwithstanding – that it becomes appropriate to talk of obesity. There are almost as many types of obesity as there are individuals afflicted by it. However, two main physical types can usually be distinguished.

      Gynaecoid obesity, so called because it is more common in women, is associated with increased deposition of fat in and under the skin – especially below the waist – and is relatively benign. Android obesity, on the other hand, is much more malign. It is more common in men and due to massive deposition of fat within the abdominal cavity. It gives rise to what is often, but wrongly, described as a beer belly. People, including women, with this type of truncal obesity have larger waist than hip measurements, and their limbs are often surprisingly thin. They are sometimes described as apples in contrast to the fancifully described pear shape of those with gynaecoid obesity.

      When truncal obesity is associated with certain biochemical abnormalities and/or high blood pressure, people with it are said to have the metabolic syndrome, but the usefulness of this term has been questioned. It is the catastrophic rise in prevalence of this truncal obesity, rather than of fatness itself, that is the major cause for concern. Neither type of obesity is an illness in its own right, but each predisposes to the development of incapacity or premature death. Diseases such as sleep apnoea, osteoarthritis of the lower limbs and hypertension are common to both, whereas diabetes and coronary heart disease are much commoner in people with truncal obesity

      Like all conditions from which mankind suffers, obesity is the result of the interplay between nature, in the shape of genetic and antenatal factors, and nurture, principally in the shape of the availability of food. While this may seem obvious, it has not always been accepted. As recently as the beginning of the twentieth century, the link between food intake and obesity was appreciated by very few. Anecdotal personal experience suggested that fat people ate no more than thin ones – some of whom seemed to be bottomless pits into which food could be shovelled with seemingly little effect. There is no doubt that this perception is wrong.

      Statistically, fat people both expend and consume more calories than thin people, although the overlap between them is enormous. This is mainly due to differences in resting metabolism – the amount of energy required just to keep the body warm – and the levels of physical activity or exercise. It is quite easy to show that quite subtle differences in food intake or energy expenditure could, over a period of many years, produce profound changes in body shape. For example, taking in the energy contained in just one knife-full of butter more than you expend every day would, after a year, theoretically cause a 2-kilogram gain in weight.

      This simplistic approach to the causes of obesity belies its complexity. What is truly remarkable is how most people manage to maintain more or less the same weight once they reach adulthood without a conscious effort to control what they eat. It is as if they possessed a ‘bodystat’ analogous to a thermostat in a refrigerator. The mechanics of this bodystat are still being unravelled by biochemists and physiologists throughout the world, and by psychologists, sociologists and epidemiologists in individual communities.

      The role of nature – genetics – rather than nurture in the process of getting fat has been known to farmers, veterinarians and experimentalists for over a hundred years, but was only recently established in human beings. This began with studies of the differences in the incidence of obesity in identical and nonidentical twins, where the effect of environment, especially access to food, could be minimised. Even more recent is recognition of the role played by intrauterine and early postnatal nutrition in the development of obesity and the conditions linked with it.

      Gross obesity occurs in several very inbred strains of rodent. In one strain the specific gene responsible was given the name ob for obesity. Only mice inheriting a copy of the gene from both parents (ob/ob) develop a condition that led to their depositing so much fat that they weighed 4–5 times as much as their siblings who did not have the gene or had inherited just one copy of it. The fat ones lacked the ability to make a hormone called leptin, which, among its many properties, has the ability to suppress appetite. ob/ob mice eat ravenously until they are so fat they cannot get to their food. Even when fed only as much as their thin siblings, they still put on more weight. Over the past decade or so a similar condition has been recognised in human beings, although it is extremely rare. Another genetic type of obesity in mice causes a condition that resembles ob/ob, but is caused by an inability to respond to, rather than produce, leptin.

      The idea that hormones played a part in controlling bodyweight began with the discovery that patients with thyrotoxicosis, caused by an overactive thyroid gland, often develop ravenous appetites yet lose weight. Conversely, those with an underactive thyroid often gain weight, though they very rarely become obese. Investigations into the role of the thyroid gland showed it played no part in the genesis of obesity. Later it was observed that many patients with rare tumours of the pancreas producing too much insulin also became very fat. In these patients with pancreatic tumours, insulinomas, this was because they were incorrectly advised to eat something when they felt symptoms of hypoglycaemia (low blood sugar) coming on rather than because it came naturally to them.

      Now that a surgical cure for insulinoma has become simpler and safer, we no longer see the gross obesity we used to associate with this condition. Nevertheless, experience with insulinomas established a role for insulin in the genesis of obesity that has now been confirmed countless times. Paradoxically, voluntarily overeating also leads to increased production of insulin and of reduced sensitivity to some, though not all, of its actions. Which, in real life, is the chicken (overproduction of insulin) and which is the egg (overeating) is probably different from one individual to another.

      Although insulin and other glandular products, such as thyroxine, cortisone and oestrogen, have long been known to be associated with obesity, it is only since the discovery of leptin that the part that hormones play in its production has been taken seriously by the scientific fraternity.

      Several new hormones, many of them produced in the intestine itself, have been discovered in the past ten years or so that affect the control of appetite and disposition of food within the body after it has been absorbed. Contrary to early expectations, most fat people have more leptin in their blood than normal, so treating them with leptin is unlikely to work except in the infinitesimally small number of people with genuine genetically determined leptin deficiency, for whom it is a ‘miracle drug’, just as cortisone was for patients with Addison’s disease and insulin for Type 1 diabetes.

      Equally exciting as the discovery of leptin is the discovery that there are at least four other hormones, all produced in the intestines or stomach in response to certain foods, that can affect appetite and metabolism of nutrients within the body. Genetically engineered animals rendered insensitive to the hormone called GIP (or gastric inhibitory peptide), for example, do not become obese with overfeeding. This observation supports earlier work, derived from studies in human beings, and suggested that GIP is one of the factors that lead people to become obese and may just be related to the composition of the diet. It also makes GIP an important target for the pharmaceutical industry to develop antagonists to its actions that can be used therapeutically.

      Contrary to popular belief, it is extremely difficult to become clinically obese by voluntarily eating excessively. This was established by experiments performed on healthy young volunteer prisoners. These experiments showed that mere access to unlimited supplies of food was not enough for the average person to become obese: something more was required. It clearly has something to do with appetite and the ability to overcome the feeling of satiety that most people experience when they have eaten sufficient for their physical requirements. One of the recently discovered hormones produced in the intestine, called PYY, works on the brain to suppress appetite

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