Human obesity: its hormonal basis and the role of gastric inhibitory polypeptide

Obesity is an abnormal expansion of the adipose organ and is a pathophysiological response to an imbalance between energy intake and energy expenditure. It is the result of a large number of diverse factors involving heritable and environmental characteristics. A simple definition of obesity is difficult and unsatisfactory and its age dependency has largely been ignored. Differentiation between healthy, age-related plumpness and obesity is often blurred and responsible for overdiagnosis of obesity in the developed world. In the past, epidemiological studies have often ignored the different prognostic significance of the two major phenotypes of human obesity making their conclusions of limited value. The role of heritable factors in determining both the propensity to develop obesity under favourable environmental conditions, including inactivity and unlimited access to fat-rich foods, and the phenotype it assumes received an enormous fillip from experiments involving genetically modified animals. The most important of these have demonstrated the key role played by a number of newly discovered or recently resurrected polypeptide hormones that are released from the intestine in response to food. Molecular manipulation of these hormones, especially of glucose-dependent insulin-stimulatory polypeptide offers a new therapeutic approach.