The identification of the obesity(ob) gene in 1994 signalled a new era of appetite research and for many brought hope for a quick and simple cure for obesity.1 The biotechnology company Amgen, who have paid $20 million for the rights to the gene product, must also hope that the ob protein will fulfil its promise as an effective appetite suppressant and treatment for obesity. At the other end of the weight spectrum, investigators have also examined the role of this protein in the metabolic response to starvation, and its potential role in the anorexia and weight loss that frequently accompany chronic inflammatory and infectious diseases.

The protein product of the ob gene, ob protein or leptin (from the Greek leptos meaning thin), is secreted into the circulation by adipose cells. A rising concentration of circulating leptin with increasing adiposity is proposed to serve as a negative feedback signal to the hypothalamus of the brain, resulting in decreased food intake, increased energy expenditure and return of body weight towards a predetermined set point. The key physiological role of leptin in the control of energy balance has been demonstrated in mice which have a mutation in the ob gene and lack functioning leptin (ob/ob mice), or have a mutation in the leptin receptor and are resistant to the action of circulating leptin2 (db/dbmice). These mice develop extreme obesity from an early age as a result of hyperphagia and a reduction in energy expenditure. Administration of recombinant leptin leads to decreased food consumption and weight loss in both normal and ob/ob mice, but notdb/db mice.3 ,4 Leptin deficiency or resistance has also been identified as a cause, albeit extremely rarely, of extreme obesity in humans.5 ,6

In healthy individuals, starvation results in a reduction …