Leptin in the pathophysiology of human obesity and the clinical potential of leptin-based therapy

Leptin is a circulating hormone that is secreted in proportion to fat mass. It can reduce bodyweight by activating signalling molecules in the brain. Leptin appears to affect bodyweight primarily by decreasing food intake; there is no direct evidence that it significantly influences energy expenditure in humans. Its discovery in 1994 raised the possibility that it may be a useful, satiety-inducing, anti-obesity drug. However, treating obese patients with leptin alone does not induce substantial bodyweight loss because most obese patients are insensitive to leptin and are not leptin deficient. In combination with diet therapy, however, leptin treatment has the potential to eliminate the dramatic fall in circulating leptin levels (and the subsequent increase in hunger) caused by calorie restriction. Used in this manner, leptin may play a very useful role in the maintenance of bodyweight loss. In the future, leptin analogues and the development of compounds that increase leptin sensitivity may also prove to be valuable therapeutic approaches for obesity.