Table 5-13. Conditions in which obesity is an associated feature

Genetic syndromes associated with hypogonadism (e.g. Prader-Willi syndrome, Laurence-Moon-Biedl syndrome)

Hypothyroidism

Cushing’s syndrome

Stein-Leventhal syndrome

Drug-induced (e.g. corticosteroids)

Hypothalamic damage (e.g. due to trauma, tumour)

Obesity is almost invariable in developing countries and almost all people accumulate some fat as they get older. The World Health Organization also acknowledges that obesity (body mass index > 30 kg/m2) is a world-wide problem which also affects many developing countries. Obesity implies an excess storage of fat, and this can most easily be detected by looking at the undressed patient.

Most patients suffer from simple obesity, but in certain conditions obesity is an associated feature (Table 5.13). Even in the latter situation, the intake of calories must have exceeded energy expenditure over a prolonged period of time. Hormonal imbalance is often incriminated in women (e.g. postmenopause or when taking contraceptive pills), but most weight gain in such cases is usually small and due to water retention.
Not all obese people eat more than the average person, but all obviously eat more than they need.

Suggested mechanisms
Genetic and environmental factors

These have always been difficult to separate when studying obesity. However, refeeding experiments in both monozygotic and dizygotic twins, reared together or apart, suggest that genetic influences account for 70% of the difference in body mass index (BMI) later in life, and that the childhood environment has little or no influence.

These refeeding experiments also showed that weight gain did not occur in all pairs of twins, suggesting that in some a facultative increase in thermogenesis occurred so that part of their extra dietary energy was expended inefficiently. Genetic factors have led to the discovery of a putative gene, firstly in the obese (ob ob) mouse and now in humans. The ob gene was shown to be expressed solely in both white and brown adipose tissue. The ob gene is found on chromosome 7 and produces a 16 kDa protein called leptin. In the ob ob mouse a mutation in the ob gene leads to production of a non-functioning protein. Administration of normal leptin to these obese mice reduces food intake and corrects the obesity. A similar situation has been described in a very rare genetic condition causing obesity in humans, in which leptin is not expressed.

In massively obese subjects, leptin mRNA in subcutaneous adipose tissue is 80% higher than in controls. Plasma levels of leptin are also very high, correlating with the BMI. Weight loss due to food restriction decreases plasma levels of leptin. However, in contrast to the ob ob mouse, the leptin structure is normal, and abnormalities in leptin are not the prime cause of human obesity.

Leptin secreted from fat cells was thought to act as a feedback mechanism between the adipose tissue and the brain, acting as a ‘lipostat’ (adipostat), controlling fat stores by regulating hunger and satiety (see below). However, many other signals are involved. It is interesting that obesity is largely restricted to humans, and animals that are domesticated or in zoos.

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