The fat of the land

March 6, 1998

It costs the NHS Pounds 2 billion a year and it afflicts almost a fifth of all Britons, but it isn't even a government health target. Julia Hinde reports on the growing problem of obesity

Britain is getting fatter. The past decade has seen a doubling in the number of fat people in the United Kingdom. The next decade, say scientists, is likely to tell a similar story. Today, 18 per cent of British women and 16 per cent of men are clinically obese. Fat-related illnesses are costing the NHS around Pounds 2 billion a year while at any one time an estimated third of the UK's hospital beds are filled with overweight patients.

The United States ranks among the world's fattest countries with 36 per cent of women, 31 per cent of men and 20 per cent of children in the obese category, (which includes those who are 20 per cent heavier than they should be for their height). In the US, 80 per cent of type 2 diabetes is directly related to obesity. Other conditions, ranging from cardiovascular disease and high blood pressure to gall bladder conditions and certain cancers, have all been shown to be directly related to being too fat.

Yet despite all this and fears of a UK "fat" epidemic next century, Britain has been slow to invest public money in obesity research. According to Gareth Williams, professor of medicine at Liverpool University, funding such research is way down the pecking order. Neither the Medical Research Council nor the Biotechnology and Biological Sciences Research Council has major research programmes covering obesity - despite it affecting almost one in five Britons. "It's crazy we are not putting more money into it," says Williams. "It's going to be one of the most important threats to our health in the future. Obesity is not even in the government's health targets anymore. We need a rational research programme,bringing people together from different fields to look at the issue."

Obesity has traditionally had a bad press. Many doctors dismiss the condition as "self induced" and there is a widely held view that "fatties" have only themselves to blame for eating too much. In recent years, however, and very slowly, views have changed. Studies of identical twins have revealed the part genes play in obesity. When a group of identical twins is overfed, the similarities in weight gain within the pairs is three times greater than between pairs.

Scientists now believe that some people have genes which predispose them to obesity. Some people can stuff their faces and never put on a pound, while others, who are genetically predisposed to being obese, will become overweight if they eat a high calorie diet and take no exercise. Nonetheless, even though genes probably account for between 40 and 60 per cent of people's susceptibility to obesity, it is environmental influences that trigger it.

The discovery in 1994 of leptin, a hormone produced in fat tissues that controls appetite and sends messages to the brain about the body's fat store, brought scientific respectability to obesity research overnight. Scientists found that increases in body fat correlate with increased leptin production, which in turn triggers reactions in the brain that suppress appetite and increase energy expenditure, eventually resulting in weight loss. But, as anyone trying to lose weight knows, it's not that simple. As fat stores decrease, the hormone that reduces appetite and increases energy expenditure also decreases, meaning people just pile back on the fat they have lost.

The gene for producing leptin was the first single gene shown to be directly implicated in making people fat. It inspired a full-scale hunt for a miracle solution to obesity with the pharmaceutical industry - desperate to locate a wonder drug for fat - among the major sponsors. But the search is turning out to be far more complex. Hopes that leptin on its own would provide a magic solution to fat are being tempered as the complexity of the human body becomes apparent.

Scientists came across leptin when investigating the ob/ob mouse, a laboratory mouse which lacks the hormone because of a mutation in its leptin gene. With no leptin reaching the brain, the mouse balloons. But when ob/ob mice are given synthesised leptin they lose weight within days. People, however, react differently. The leptin levels of most fat people are perfectly normal, so scientists are doubtful whether injecting leptin will help reduce weight.

Scientists are now looking at the possibilities of leptin resistance in humans - fat people may be producing leptin in quantities related to the amount of fat stored in their bodies, but perhaps the messages are not getting through to the brain. Jose Caro, a scientist at the Lilly Research Laboratories in the US, told last month's American Association for the Advancement of Science meeting in Philadelphia that there was some evidence to suggest that blood leptin levels in some overweight people could be up to five times greater than in thin people, yet when leptin was measured in fluid entering the brain, levels were sometimes only 20 per cent greater. Other scientists are trying to understand what happens once leptin enters the brain as well as why metabolic rates differ between individuals.

In all this research, it is becoming clear that leptin may be just the tip of the iceberg for understanding the neuro-chemistry of obesity. Other hormones, including insulin and steroids, certainly affect weight gain and metabolism, while it has been found that leptin has other roles, being involved, for example, in reproduction. So interfering with people's leptin levels in a bid to shed fat may have unwelcome side-effects.

According to Paul Trayhurn, assistant director at the Rowett Institute in Aberdeen and co-organiser of a conference on leptin held in London last month, we could now be looking at anything from a dozen to hundreds of genes affecting metabolism and weight control. A combination of several subtle gene defects might be sufficient to leave someone susceptible to obesity.

At the end of the day, Trayhurn says he is certain we will develop drugs to help. "But I don't think we should think of a single magic bullet where people are able to eat as much as they like and pop a pill to counter it." With commercial interests now getting behind the drive for a quick fix solution, some scientists fear we are in grave danger of having the whole obesity research agenda set by pharmacological treatments. They stress that obesity is a late 20th-century disease. It is not our genes that have changed - that would take generations - but the environment within which we live - the food we eat, the sedentary lifestyle we choose to lead. It is the environment, not genetics, that is making Britain fat.

Susan Jebb, a scientist at the MRC Dunn Research Centre in Cambridge, says:

"Even the most ardent geneticists agree that genes only provide a predisposition to obesity. What people choose to do in their lives will ultimately decide whether they get fat. We must take care to ensure that amid the scrum for pharmacological therapies, we pay attention to behavioural determinants of obesity too. Humans all make choices every day about what they eat and how they live their lives.We need to try to understand what motivates people to make the choices they do. The genetics of obesity is important. But understanding human behaviour is the other mountain we have to climb if we are to win the war on weight."

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