4th quarter 2004

Obesity is on the rise

Human genes poorly adapted to cope with oversupply of food

New findings may help to improve prevention and treatment

More and more people are overweight, resulting in increased morbidity (e.g. diabetes, hypertension, high blood cholesterol) and mortality (e.g. myocardial infarction and stroke). This unwelcome trend can be found in virtually all societies where there is an oversupply of food. The principle reason for this is that in the course of an evolutionary process lasting many thousands of years, humans have developed the ability to derive maximum benefit from the food they ingest. Famines have been a regular occurrence in the last few centuries, and those able to get maximum use from food had a significantly better chance of surviving. Others, who, due to their genetic disposition, needed large amounts of food to maintain their body functions, were more likely to die during periods of famine. This is why, over time, the genes responsible for sub-optimal use of ingested food decreased in the overall population. In the last few decades, the availability of food has steadily improved. Food has become cheaper, and its calorie content has increased ("fast food"). Most people are unable to cope well with this oversupply. They eat too much and become fat. In the US, over 50 per cent of the population is considered overweight. Recently, this problem has increasingly affected children as well. The trend is exacerbated by a decline in physical activity (people watch TV and play computer games instead of engaging in sports and exercise).

There is broad consensus among scientists, doctors and public health and social security policymakers that this issue needs to be addressed urgently. In the US, even an international life and health reinsurer has joined in the effort to raise public awareness of the problem, pointing out that premiums may rise in response to the increased risk.

The battle against the obesity epidemic is, in some respects, a battle against human genetic disposition. During the last few years, it has become more and more clear that diabetes, disorders of fat metabolism, hypertension and obesity share a common genetic component. About half of the causes underlying these disorders can be attributed to genetic factors. It is difficult to draw a clear line between genetic and non-genetic causes, however, because such complex processes as eating habits, a feeling of being "full up" and physical activity are also partly determined by genes. Currently, 340 different genes are known to play a role in weight regulation. Most of them tend to promote obesity. Recently, it has been reported that inactivation of a specific gene (S6 kinase 1) helps to prevent obesity and diabetes. Other genes have a protective effect and lower the risk of becoming overweight.

It is common knowledge that diets often fail. Frequently, this is attributed to poor compliance on the part of the dieters. However, if overweight people say "I just can't exercise" or "I can't resist food", they are describing a behavioural pattern which does not seem to be exclusively acquired by learning, but is at least partly determined by genetic factors. Overweight patients have been found to have mutations in the genes that control behaviour and sensation (e.g. neurotransmitter metabolism).

It is helpful to identify these mutations (drug targets) in each individual case in order to design an appropriate treatment plan. The pharmaceutical industry is also looking at ways to exploit these findings to develop effective drugs. The French company Sanofi-Aventis is currently testing a "miracle pill" (Rimonabant) on 13,000 subjects. It is supposed to help people not only lose weight, but also stop smoking.

As is most often the case in medicine, prevention rather than treatment is likely to be most successful in achieving the desired effect. The aim is to avoid putting on too much weight in the first place. Obviously, this should start in childhood.