PEOPLE who volunteer to be human guinea pigs in James Stubbs’s lab on the outskirts of windswept Aberdeen need few special attributes save one – a liking for their own company. Some volunteers are expected to spend seven days in solitary confinement in a small cell equipped only with a toilet, wash basin and two luxuries: a TV and exercise cycle.
But at least they are well fed. Through an air-locked hatch in the door, researchers deliver ordinary-looking meals prepared with extraordinary precision. They control, down to every last gram, the relative amounts of fat and carbohydrate that go into each subject’s body. And they monitor exactly how much oxygen its respiratory system consumes and how much carbon dioxide it produces. For their part, subjects are expected to write down, once every waking hour, how hungry they feel. In short, they become self-reporting, controlled thermodynamic systems – a means of studying how fast the human body burns off different kinds of nutrients, protein versus carbohydrate versus fat; a means, too, of studying how these different nutrients affect the human appetite.
At the end of their week in the “whole body calorimeter” the guinea pigs receive £70 from the Rowett Institute in Aberdeen, where Stubbs and his nutritionist colleagues make their measurements. But their greater reward is the edifying knowledge that they have helped in some small way to further science’s understanding of that great bane of Western affluence: the rise of obesity.
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Stubbs sees the human body as an engine which must burn up its fuels in a specific order – alcohol first, then protein, then carbohydrate, and finally fat. And this hierarchy, he maintains, is crucial to understanding obesity. Not, as you might imagine, because the order means our bodies never quite get round to burning off the excess fat we eat; but because of how the hierarchy influences our appetites, and in particular how the lowly position of dietary fat encourages people to carry on eating burgers and ice cream well after their energy needs have been met.
It may sound confusing, but then the science of what makes some people fat and others thin is replete with theories that can seem as topsy-turvy as anything in quantum physics. Folk wisdom, for example, sees obese people as victims of slothful metabolisms. Yet three decades of research have failed to find any metabolic differences between fat and thin people that explain weight variations. In fact, obese people end up burning more calories as their larger bodies require proportionately more chemical fuel just to keep ticking over, and more still to move. Nor does thinness seem to be the work of “brown adipose tissue”, the heat-producing fat found in smaller mammals and newborn babies which was all the rage in the late 1970s and early 1980s as an explanation of human weight differences. Indeed, obesity researchers are wont to joke that after 30 years of research – analysing human eating habits, scrutinising the chemistry of fat cells, studying the genetics of lab rodents that make human couch potatoes look positively lithe – they have come up with only one unassailable fact: overeating makes you fat.
Doomed diets
And even then they are not necessarily talking about weak-willed people gorging on cream cakes. Such are the cumulative effects of “overeating” that you only need to misjudge your energy needs by 1 or 2 per cent every day to end up many kilos heavier at the end of a year. A slice of toast a day can make all the difference between staying lean and getting fat. In a park-and-ride world awash with high calorie foods, the remarkable thing is not that some people become obese; but that the various mechanisms controlling our appetites, behavioural as well as biological, manage to achieve any kind of balance between energy intake and needs.
But achieve it they do, and working out how they do so (and why they sometimes fail) has become a priority in the crusade against obesity. And while the picture emerging from nutrition labs like Stubbs’s is increasingly complex, the starting point at least is simple: why does dieting so often fail? Why do generations of dieters tell the same sorry tale of lost pounds returning with a vengeance?
Rudolph Leibel, a nutritionist at the Rockerfeller University in New York, and his colleagues believe they have found the answer – and it has nothing to do with a lack of willpower. As our bodies develop, claims Leibel, they “seek a set point” in weight and composition which stubbornly resists change. Try to exceed your set point weight, and your body will quietly rebel by jacking up the rates at which it burns energy. Attempt to burrow beneath the set point through dieting, and the reverse happens. Either way, the body reacts to restore its weight.
Last month, Leibel and his team published what is arguably the strongest evidence so far for this idea. In the New England Journal of Medicine, the researchers reported how the energy needs of volunteers – 18 obese subjects and 23 who had never been obese – responded to weight gain or loss. Over eight years, these human guinea pigs spent various stretches living in accommodation attached to Rockefeller University. For up to 120 days at a time, they ate fixed-calorie meals and allowed researchers to record reams of metabolic data – the calorie contents of their excretions, the amount of energy consumed by their bodies at rest at various times of day, how fast they burnt off calories taking physical exercise, how much energy their bodies consumed keeping warm. Some subjects even spent whole days in a respiration chamber equipped with wall-mounted radar detectors to monitor physical activity.
As expected, there were no differences between the metabolisms of obese and nonobese subjects allowing for variations in body mass. Nor did obese subjects respond any differently to gaining or losing weight. In both cases, the bodies of subjects who increased their weight by 10 per cent compensated by increasing the amount of energy they used up, mainly during periods of physical activity, but also just in keeping the body ticking over at rest. Those who lost 10 to 20 per cent of their body weight did the opposite: their bodies responded by using up 10 to 20 per cent less energy at rest and during physical activity.
Silver lining
Inevitably, the lost pounds flooded back. But Leibel sees a silver lining in the cloud: “The obese participants can at least take comfort from the fact that we’ve shown experimentally that there is a biological side to the problem; that they are not lazy, slothful or gluttonous.” So can failed dieters everywhere. “It’s not your fault,” says Leibel, if the pounds come back. “People in the dieting industry have known about the effect all along. Most of their business is repeat business.”
Few nutritionists would argue with the notion of bodies trying to defend particular weights. After all, there are good evolutionary reasons why they should behave this way. Where researchers diverge is over just how set the set point is. At one extreme, Leibel and others say that the “rebellion” triggered by a period of weight loss can persist for months and perhaps years. But others say the evidence for this is still equivocal and that bodies sometimes readjust to lower set points relatively quickly.
Opinions also differ as to what the rebellion means for people desperate to shed pounds and keep them off. The answer, says Stubbs, depends on whether it is caused mainly by shifts in metabolism or levels of physical activity. Consequently, some see developing new drugs as the best way of quelling it, others physical exercise. “Knowing that your body is trying to compensate for the weight you’ve lost is an incentive for fighting back with more exercise,” says Barbara Rolls, who studies appetite control at Pennsylvania State University.
Moreover, even if dieters are at the mercy of stubborn mechanisms that seek to keep weight fixed, there is another question to debate: what fixes the set point? Genes? Overeating early in life? Hormones acting on the brain? A slothful adolescence? “We don’t know exactly,” says Leibel. “But it is clear that there is a strong genetic component.”
Born to be fat?
This idea received a boost last autumn when Jeffrey Friedman and his colleagues at the Howard Hughes Medical Institute in Rockefeller University identified a defective gene called ob which makes rats gorge themselves into a state of obesity. It isn’t the first gene of its kind to be discovered in lab animals. But there are special reasons why many researchers are excited about the ob gene. The healthy version of the gene encodes a protein produced only in fat cells, suggesting that there could be a direct link between the chemistry of fat cells and appetite control. Not only that, but the protein seems to have the chemical structure of a signalling molecule, a hormone that could, just conceivably, be the initiator of “no need to eat” signals to the brain. Were such “satiety molecules” to exist in humans they could be key players in setting the set point body weight.
But all this is still speculation, and it is not hard to find sceptics. “The ob gene is just a gene that fat animals have,” says Michael Goran, a researcher at the University of Alabama, Birmingham. “We don’t know if it influences satiety or [physical] activity, or something else.”
Even if the research into genes like ob delivers what it promises – targets for researchers looking for drugs to retrain appetite – genetics alone cannot explain the wave of obesity now engulfing the West. Genes just don’t change that fast. There has to be something about our food and increasingly sedentary lifestyle that brings out the worst in our genes, making our bodies seek, and then defend, higher weights than are good for us.
The food industry and its ad campaigners hold up dietary fat as the enemy. “Very few of us get through the day without being bombarded by some warnings about fat,” says Rolls. “People are so afraid of fat now,” she says, commenting on the huge switch in recent years from calorie-controlled dieting to fat-controlled dieting.
Some of those fears are misplaced. Calorie for calorie, dietary fat is no more fattening than carbohydrate or protein. Nutritionists have shown as much by putting subjects on diets that are equal in energy but vary wildly in the amounts of fat and carbohydrate they contain. As Leibel puts it, “a calorie is a calorie is a calorie”.
This is not to let dietary fat off the hook, however. Far from it. The real danger with fatty foods, says Rolls, is that they are much easier to “passively overconsume” than are foods rich in carbohydrate or protein. Not only does fat taste good, but it is very dense in energy, a gram of butter containing twice as many calories as a gram of starch. And there may be another, more subtle reason why fatty foods encourage overconsumption. More and more evidence suggests that dietary fat is a much poorer appetite suppressant than is carbohydrate, which is in turn poorer than protein. Fatty foods produce weak “satiety signals”, says Stubbs. Or in plainer terms, they just don’t fill you up.
Hardly news, perhaps, to those who continually seek, yet seldom find, satisfaction in burger bars. But establishing as much scientifically has been no easy task. In one of the latest studies, Rolls and her colleagues repeatedly sneaked varying amounts of fat or carbohydrate into their subjects’ yoghurts. The researchers then monitored how much additional food the volunteers went on to eat at lunch. A dozen normal-weight men, with no interest in dieting, accurately compensated for the energy in the yoghurts, whether it came from fat or carbohydrate. But the opposite was true for a dozen obese men and women. They failed to reduce the size of their lunches in an orderly fashion. Not only that but, calorie for calorie, the fatty yoghurts suppressed their appetites much less than did the carbohydrate-rich yoghurts.
No satisfaction
Rolls, for one, is certain of the message: “Obese people have an impaired satiety for fat.” Whatever this impairment involves – defective genes or maladapted sensory systems or something different again – it could be crucial to why obese people stay obese; why their set-point weights remain stuck at unusually high levels. Rolls also believes that our inability to handle fat explains why many people put on weight in the first place. “It’s much easier to gain weight on a high fat diet,” she says.
But here’s the rub: low fat diets are not necessarily the best route to shedding pounds and keeping them off. Today’s obsession with fat-free food is enouraging people to take their eye off the calories, says Rolls, who argues that restricting the amount of fat in a diet, but not the total number of calories, leads to less weight loss than restricting the total number of calories. “Ads that suggest you can eat as much cheesecake as you want provided it contains little or no fat are misleading.”
Working out why fat is such a weak appetite suppressant compared with carbohydrate and protein involves other twists of logic. The standard theory points to strong appetite suppression from carboydrate. People eat to maintain a certain amount of carbohydrate stored as glycogen in the liver. Once these stores are topped up some kind of satiety signal is sent to the brain. The problem with high fat diets is that they displace carbohydrate as a proportion of dietary energy. As a result, people need to consume more calories to produce an equivalent satiety signal.
But this theory is too simplistic, argues Stubbs, who believes the key reason people are more likely to overconsume fat than carbohydrate is that fatty foods are normally very dense in energy. Nor is that all. Based on studies of how people in whole body calorimeters respond to different diets Stubbs argues that carbohydrate stores are not the only things producing the feedback that reins in appetite. Also important is how fast the body is obliged to burn off nutrients surplus to needs. The body’s capacity for storing carbohydrate is limited to 900 grams; and only a small amount of protein can be eaten before the excess must be burned off. So the body has to move fast after a meal to burn off any excess carbohydrate or protein – and it is this process that produces strong satiety signals. In contrast, the oxidation of alcohol or surplus fat produces only weak satiety signals. Burning off calories of alcohol may be essential to avoid the toxic effects of the drug, and burning off calories of fat may be necessary if you haven’t eaten much carbohydrate, but neither produces much sensation of fullness.
Through the maze of complexity, two things are at least clear: fat is the only nutrient for which the human body has virtually infinite storage capacity, and it is the only one we have problems handling. That could mean our ancestors were never exposed to sufficient dietary fat to evolve effective biological mechanisms for dealing with it. But more likely it is adaptive (why else would we find fatty foods so palatable?). Back in the Pleistocene, 200 000 years ago, food supplies would have followed a boom and bust pattern, making it a plus to be able to store calories of fat. In a world of hypermarkets and TV meals, that has become a handicap.
Overweight and underage
KIDS today might look like they are piling on the pounds but that doesn’t mean they’re eating more. Quite the opposite: children in the 1990s consume, on average, 20 per cent less food than their slimmer counterparts did in the 1960s. If they are fatter it is because their energy expenditure has dropped.
The evidence comes from new and much more accurate techniques for measuring energy use, even in babies and children. Expenditure and intake normally balance more or less exactly. But these techniques show that children expend on average 25 per cent less energy than the WHO recommends they need to take for their age.
Either the WHO miscalculated when it drew up the guidelines a decade or more ago, or children have become markedly less active. Peter Davies, head of a team that has been studying children at the MRC’s Dunn Nutrition Laboratory in Cambridge, is sure which explanation is correct. “Children spend much more time in front of the TV or playing computer games; they travel by car rather than cycling or walking; because of fears about their safety they are far less free to roam and play outside than they were two decades ago.”
The Dunn Laboratory is one of a small number of centres around the world which have made great progress in measuring energy expenditure using doubly-labelled water. Children take a drink of water containing two harmless, non-radioactive atomic isotopes, one of hydrogen and one of oxygen. Over the next week or so, they produce urine samples each day for analysis. The technique shows how much energy children use because the more energy they burn up, the more carbon dioxide they produce, and the faster the labelled oxygen disappears from their bodies relative to the hydrogen.
The result is a measure of total energy use. This is made up of several components. The largest, called the resting energy expenditure, is the amount needed to keep all bodily systems ticking over at the minimum level. In children it accounts for 60 to 70 per cent. Thermogenesis – keeping your body at a constant 37°C – takes up another 2 to 3 per cent, but central heating and warm clothing reduce this. Growth, surprisingly, is not a major energy-consuming process after the age of one year – perhaps another 1 to 2 per cent. The rest of the energy is burned up during physical activity – the only component over which we have much control.
So are fat children simply less active than lean children? Davies used the doubly-labelled water technique to measure how much energy a group of 77 children all under five, expended over 10 days. The ratio of this figure to resting energy produced an index of physical activity, from which Davies could indeed deduce that the fatter children were less active than the leaner ones. Such trends do not, however, prove cause and effect.
Perhaps obesity is less the result of inactivity as of a sluggish metabolic rate? Here again the new techniques are beginning to settle an old debate. But it’s a complicated story. For a start, obese children expend more energy, not less, than their lean classmates. Their larger bodies require more fuel, not just to keep ticking over, but also to carry the extra weight. Therefore it makes more sense to look at energy expenditure per kilo of body mass. On this basis, it’s the lean children that burn more energy, even when resting.
But this doesn’t mean that children become overweight because of a slower metabolism. Michael Goran, a researcher at the Energy Metabolism Research Unit in Birmingham, Alabama, and his colleagues have shown that fat tissue consumes energy at only around a third the rate of muscle fibres and organs such as the brain and liver. After allowing for differences in body composition, Goran concludes that there is no difference in resting energy expenditure between lean and obese children.
So much for the output side of the equation. What about the input side – how much children eat, and what kind of food? Jeannie Gazzaniga and Trudy Burns, at the University of Iowa, carefully recorded what a group of schoolchildren ate over three days and how much energy they used. The obese children ate more, but only in proportion to their size. In fact, kilo for kilo of body weight, the obese children took in fewer calories than did lean kids. What Gazzaniga and Burns did find, however, was that the obese children ate less carbohydrate and more fatty foods – crisps, biscuits and sweets.
The fat of the land
THEY call it the generation X disease – and it is easy to see why. In Britain, the proportion of obese adults has doubled in the past 10 years, to 13 per cent of men and 16 per cent of women. And according to the latest figures in the US, one in every three adults, and perhaps as many as one in four 10-year-olds, is now obese.
Obese people have a body mass index (weight in kilograms divided by the square of height in metres) of more than 30, the desirable range being 20 to 25. A man measuring 1.75 metres, for example, is defined as obese once he reaches 92 kilograms – a weight that would put him at high risk of depression, diabetes, high blood pressure and coronary heart disease.
More startling even than the proportion of obese people is how fast their numbers are growing. One study of Canadian children of all ages found that 50 per cent more were obese in 1988 compared with 1981 – a mere seven years. The National Diet and Nutrition Survey of children aged 18 months to four and a half years, published last month, indicated that British toddlers were no fatter in 1992 and 1993 than 25 years previously. Yet all the evidence suggests that somewhere between starting school and adulthood, an increasing proportion of them will become overweight and then obese. The question is, why?