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 – so does the even more recently discovered hormone obestatin.
Under experimental conditions, PYY enables obese people to resist the temptation to eat excessively. It is currently being pursued as a potential treatment for obesity. Other gut hormones affecting appetite and the sense of satiety are also known. One of them is called is GLP-1. Like GIP and PYY, it is made and released from the intestine in response to certain foods; like GIP, it is involved with the disposition of the individual constituents of the food within the body, mainly – though not exclusively – through their ability to stimulate the release of insulin. It, or something very like it, is already available commercially for the treatment of Type 2 diabetes. Ghrelin and obestatin, both discovered within the past ten years or so, are produced in the stomach and affect appetite in opposite directions: ghrelin stimulates appetite; obestatin inhibits it.
Just how important the newly discovered hormones are in deciding whether or not you become obese is still uncertain. It’s one thing to discover how a hormone works under research conditions, quite another to apply it in a clinical situation.
We are still a long way from understanding how these new hormones work in human beings under everyday living conditions. Studies on the changes produced in grossly obese patients whose only salvation comes from by bariatric surgery – operations on the stomach that are currently the only effective method of treating this life-threatening condition – will undoubtedly advance our knowledge. So will experiments and clinical trials using pure hormones as they become available, exactly as happened with insulin and diabetes.
While the availability of a plentiful supply of food is a prerequisite for the development of obesity, the relationship is far from being a simple one. Most people with access to alcohol do not become alcoholics; a few, especially those with a genetic predisposition, do. The same is true for food, but whereas it is possible to abstain from alcohol completely – and so achieve a cure of the ill – this option is not available to the obese. Obese patients may find it comparatively simple to stick to a very low-calorie, synthetic, liquid, formula diet and lose weight at just about the maximum theoretical rate – about half a pound or a quarter of a kilo a day – but as soon as they are permitted to replace one of the meals with solid food of their own choosing they stop losing weight and may even gain it.
The idea currently being propagated by single-issue pressure groups is that obesity is due to one particular type of food constituent, whether it be fat, sugar, rapidly absorbed starches or combinations of them – in particular when they are provided in the form of foods such as hamburgers, pizzas, chips, crisps and other energy nibbles. This would be laughable if it were not so misleading. Obesity is a genuine, recognisable medical problem. It will not be resolved by simplistic dogma that is based on unproven opinion rather than on evidence.
The fact that an increase in the incidence of obesity coincided with a rise in the availability of fast or convenience foods is not evidence of their role in its causation. Exactly the same argument could be advanced for the rise in the use of telephones, or – better – central heating. Human beings burn off many more calories to stay alive in a cold environment than when they are warm. It would nevertheless be as foolish to assume that the answer to obesity is to return to the days of cold and damp housing as it is to suggest that banning the sale of energy-dense fast foods, or labelling them as bad for you, will the solve the problem. Decades of dietary advice for the prevention and treatment of obesity based on avoiding first this and then that type of food have all resulted in failure.
Any new way of losing weight is likely to produce an effect lasting a year or two, especially if aided by pharmaceutical appetite suppressants. A small percentage of dieters do manage to sustain their weight loss, but this is achieved not merely by changes in their diet but by altering their whole way of life. Indeed, the few long-term, large-scale interventional studies that have succeeded in reducing the incidence of obesity, and more especially Type 2 diabetes, have relied upon intensive re-education and alterations in lifestyle to incorporate changes in exercise as well as in eating habits. The importance of moderate and regular exercise in achieving weight loss cannot be overemphasised – not because of the calories consumed in doing it but for its general effect upon the metabolism of the body.
Other factors are important also. The way food is eaten, whether as regular meals or ‘on the hoof’, the time of eating, the size
