Fat, Fate, and Disease : Why we are losing the war against obesity and chronic disease (5 page)

So we need to ask the right question: how can we reduce the burden of non-communicable disease? It is only within the framework of this more direct question that obesity becomes relevant. Not all fat is necessarily bad. For example, steatopygia—the technical name given to the large fat stores on the buttocks which are particularly prominent in peoples of sub-Saharan African origin—is a big fat deposit but it does not do any harm. There is no evidence that having steatopygia affects the risk of disease. Indeed it is thought to be a special adaptation which evolved to allow humans to live in unpredictable environments by storing energy in the form of fat for periods when food was not plentiful. We need to see beyond fat itself to understand why it is that excess fat in some parts of the body and in some people is not good.

Fat is complicated stuff. Of all the components of the human body it is the one which varies most between individuals. It is generally considered healthy to have about 15 per cent of one’s body made up of fat if one is male and about 20 per cent if female, although some of us have less than that. This proportion of fat, about one-sixth of the body, is probably about the same as that of our ancestors in the Rift Valley in Africa in the early stages of human evolution.

For many years we have viewed fat simply as a storage depot, a source of spare energy which we carry around with us, rather in the way that we might take a snack or even a packed meal on a long journey. As a species we do not graze more or less continuously while we are awake, unlike many large vegetarian mammals. Rather, we eat substantial meals at intervals and can then go for many hours—for example when we sleep—or even days in between.

Fat is different from protein and carbohydrate, not only in its chemical structure but also in the amount of energy it stores. This is important because the body uses energy to run all its machinery. This energy is generated by organelles within cells called mitochondria which use oxygen carried by the bloodstream to burn the fuel supplies available to them. This is very similar to a stove which creates energy in the form of heat by using oxygen from the air to burn wood or coal or natural gas. And just as these fuels generate very different amounts of heat, so is fat different from the other possible body fuels. One gram of fat produces 9 calories, more than twice the amount of energy produced by burning protein or carbohydrates. This is why fat is the energy store of choice for a camel, a migrating bird or insect, or any other animal that faces long periods without access to food as part of its life.

We not only eat fat and store that fat in our bodies, but if we have excess energy intake from other sources, we can also convert carbohydrates, particularly alcohol and sugars, and even protein
indirectly into fat. So any form of energy we consume can, under some circumstances, end up as fat.

Life is all about energy—without it we are dead. Everything our bodies do requires energy—our brains use a lot of it; so do the heart as it pumps blood and our intestines as they digest and absorb food. Every aspect of body function is energy-dependent. Then of course we use energy to keep warm and when we move our muscles as we walk or run, when we stand, even when we fidget. Different forms of exercise and activity consume different amounts of calories (or kilo-joules, which is another measure of energy; 4 kilojoules equal about 1 calorie). Growth also requires energy to convert food into new body tissues—and reproduction shifts fuel supplies to the fetus as we build the next generation.

So, when we look at fat we see that it is not an inert, static part of our bodies like the snack we might carry in a pocket. The fat stored is the result of the balance between ‘energy in’ in the form of food and ‘energy out’ in the form of our normal body functions and of growth, reproduction, and exercise. Essentially the only way we have to store excess energy is in the form of fat, so if we eat more energy than we expend there is only one way in which that excess energy can be stored, and that is as fat. Similarly, if we expend more energy than we consume, we usually lose fat. There are exceptions which can lead to muscle and protein loss but these are associated with disease such as cancer.

We all need some fat in our bodies—we would not survive without it. Indeed when we are born we are the fattest species on the planet—human babies at birth are fatter even than baby seals or whales. For many years it was assumed that we evolved to have fat babies because fat, as a good insulator, keeps babies warm—this is why adult polar mammals like whales and seals have so much blubber. But we now know that this is not likely to be the reason—after all, our ancestors were born into hot climates in Africa. Our exceptional fatness at birth is probably due to the newborn baby’s development being dependent
on having spare energy to protect its very energy-dependent brain growth, particularly if its energy intake becomes limited by illnesses such as diarrhoea. Such illnesses were historically very common around the time of weaning when the infant starts to consume a range of new foods. Unlike its mother’s breast milk, which is virtually sterile, these new foods contain all sorts of pathogenic organisms. These diseases are still very common in the developing world where diarrhoea remains a major cause of infant death—and death is far more likely if the baby is chronically under-nourished and has inadequate fat stores.

Until recently much of the focus of obesity research has been based on the concept of the energy balance equation, namely that the amount of fat you have is the outcome of the balance between energy taken in as food and energy expended by muscular activity, maintaining the body, and even thinking. So some people store more fat either because they have eaten more over a sustained period of time or because they have expended less energy over that period of time. The only way to change the amount of fat in their bodies is for them to eat less or to expend more energy. There is truth in this idea, but only some. It is certainly true that we can lose weight by taking up an active sport or adopting a daily exercise regime. Marathon runners and even habitual joggers are often fairly thin. But then they often eat substantial meals and indulge in snacks too. So it is not just that they have burnt off more fat, because they seem to be taking on board more energy as well. It is almost as if the throughput of energy, from food taken in to energy output, has been increased, like a car with a slipping clutch that uses a lot of fuel to go any distance.

Equally, many of us know how difficult it is to lose fat by dieting. Limiting how much we eat will usually lead to some loss of weight, but very often we put it back on again even though we maintain a strict diet. No matter how determined the slimmer becomes in terms of restricting his or her calorie intake, somehow the body just seems
to become more efficient at fuel usage and at keeping up the body’s fat stores. Indeed we are now finding that there is some very complex brain and hormonal biology that tries to restore our weight to what it was originally. That is why few people can sustain weight loss over many years.

This brings us to the idea that we all have a set point for regulating the level of our body fat. It is not simply that any calories ingested and not burnt in energy expenditure are stashed away as fat globules. It appears that the level of fat in our bodies is carefully controlled from day to day and from year to year throughout our lives. The control sets how much and what we eat, how much energy we are willing to expend in physical exercise, how we control our body temperature, and even how much energy we waste everyday by fidgeting or save when we are inactive or asleep. These processes are underpinned by some fundamental aspects of our biology.

Fat is not just like the balance of money in a bank account at the end of the month, when we try to weigh up how much we have spent against how much we have earned. That balance is controlled by how profligate or abstemious we have been in the month and maybe how much our employer has deigned to pay us. The balance is the result of the operation of the two opposing processes of spending and being paid, something which control engineers call an ‘emergent property’ of the system. But with fat it is the very level in the body itself which is controlled. The financial analogy would be that we must retain £1,000 in our bank account at all times, so we then regulate our expenditure or our earnings in order to maintain that balance on a day-to-day basis. Here the engineer would say that it’s the spending or the taking on of more or less employment in order to maintain the £1,000 balance which forms the emergent properties of the system.

But how is the level of fat in the body controlled? Or, to put it another way, how does the body know how much fat it has? The bank account analogy doesn’t help very much here, because, after all, you can use your debit card to buy a new pair of shoes for £50 just as easily if you have £100 in your account as if you have £1,000 in your account. And equally, you can deposit money into your account just as easily no matter what the balance is. The regulation of spending or earning is not directly related to whether we set our desired minimal balance at £1,000 or £10. We can regulate that balance only by taking a reading of it, say from the internet or a cash machine. So the body must have a sensor, some means of detecting how much fat is stored, which must somehow interact with the systems which regulate how much fat there is.

But fat is not just a passive storage system like the gas tank in a car or your bank account. Research over the last 20 or so years has shown that fat produces a range of hormones which affect the ways our body works. The most well-known hormone made by fat cells is called leptin. Leptin enters the bloodstream, and when it reaches the brain it affects appetite. High levels of leptin suppress appetite and give us a sense of being satiated. Leptin can also affect other organs; for example the pancreas, where it alters the amount of insulin made to control blood sugar. There are other hormones which also affect our appetite control, some of them made by the stomach in response to food, of which the most important is called ghrelin. When the stomach is not full it secretes ghrelin, which stimulates our appetite—so we start looking for food.

The importance of the satiety hormone leptin can be seen from observations on children who have a genetic defect which prevents them from producing a functional form of the hormone, or whose appetite and satiety control centres in the brain are resistant to it. A team in Cambridge led by the ebullient and talented scientist Steve O’Rahilly, who is both a clinician and a molecular geneticist, have studied such children. They are exceptionally obese. They are almost unable to move around and certainly not able to join their friends in
playing sport, dancing, or riding a bicycle. They are driven by an insatiable appetite, to the point where they absolutely have to eat. Some of them have been known to raid the freezer in the middle of the night to eat uncooked frozen food to satisfy this craving. Steve and his group are adamant that these children are not just greedy, and there is very little that they can do about the problem themselves. Nor is it simply like a drug addiction. It is not just because they have developed a taste for ice cream and chocolate sauce and have a habit they cannot break. The setting of their appetite control is fundamentally wrong. But for those rare few who have a genetic defect that hinders their production of functional leptin, treating them with doses of synthetic leptin hormone can help them to lose huge amounts of weight and restore their lives to some semblance of normality.

And when we lose weight, our plasma ghrelin levels tend to rise and our leptin levels fall. These two hormonal changes act on our brains to make us eat more and return to our original weights. These changes can be seen even years after weight loss. This makes sustaining weight loss very difficult.

But not all fat is the same. From the perspective of metabolic disease the most important fat is not the fat directly under our skin, at least that fat under the skin on our arms and legs and back, although there is an exception which we will soon discuss. This fat seems quieter in a hormonal sense—some experts have argued that it simply provides a way of storing energy and, unless it contributes to morbid obesity and interferes with breathing and weight-bearing, it is not harmful. Fat is also stored in breast tissue in women because healthy pregnancies and lactation require an adequate energy store, as reflected in adequate fat stores. Sexual selection theory in evolution would also suggest that males choose their mates partly on the basis of their breasts because this aspect of the body’s shape can represent fertility.

Instead it is the fat deeper inside our bodies that really plays a major role in influencing whether we are healthy or not. This is the
fat we cannot see. It is normally found lining the inside of the abdomen and in the membranes supporting the intestines. Technically this is called visceral fat. This fat is metabolically very easy to mobilize and indeed we use it to provide energy to deal with short-term fasting for a day or so. This can happen if we are ill but it might have been very common for our hunter-gatherer ancestors at times when no food could be found. Visceral fat also has very different biological functions from fat under the skin because it makes different hormones and inflammatory compounds. As our fat stores increase, we deposit excess amounts of this internal fat, not only in the intestinal membranes but also inside our livers and even inside our blood vessels and hearts. This is not healthy and is associated with a change in the way these organs work and how they respond to insulin. When this happens we are on the path to diabetes and cardiovascular disease.

But it turns out that some fat deep under our skin on the abdomen is biochemically very similar to visceral fat. Thus unhealthy obesity is generally associated with increases in fat both inside and outside the abdomen. That is why having obesity centred on the abdomen is a particular risk factor, and we can assess it by measuring the ratio of waist to hip circumferences, or simply our waist circumference.