Recently we reported the dramatic and beneficial effects of daily subcutaneous injections of leptin reducing body weight and fat mass in three congenitally leptin-deficient children (Farooqi et al., 1999; 2002). The major effect of leptin was on appetite with normalisation of hyperphagia. Leptin therapy reduced energy intake during an 18MJ ad libitum test meal by up to 84% (Farooqi et al., 2002). We were unable to demonstrate a major effect of leptin on basal metabolic rate or free-living energy expenditure, but, as weight loss by other means is associated with a decrease in (BMR) basal metabolic rate, the fact that energy expenditure did not fall in our leptin-deficient subjects is notable. The administration of leptin-permitted progression of appropriately timed pubertal development in the single child of appropriate age and did not cause the early onset of puberty in the younger children (Farooqi et al., 2002). Leptin also reversed the T cell dysfunction and caused a switch from a predominantly TH2 to a TH1 immune phenotype (Farooqi et al., 2002).
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