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; th ere is no direct evidence that it significantly influences energy expenditu re in humans. Its discovery in 1994 raised the possibility that it may be a useful, satiety-inducing, anti-obesity drug. However, treating obese patie nts with leptin alone does not induce substantial bodyweight loss because m ost obese patients are insensitive to leptin and are not leptin deficient. In combination with diet therapy, however, leptin treatment has the potenti al to eliminate the dramatic fall in circulating leptin levels (and the sub sequent increase in hunger) caused by calorie restriction. Used in this man ner, leptin may play a very useful role in the maintenance of body weight l oss. In the future, leptin analogues and the development of compounds that increase leptin sensitivity may also prove to be valuable therapeutic appro aches for obesity.