Who might benefit from leptin therapy?
The discovery of leptin in 1994 raised hopes that it might represent a panacea for the huge public health problem of obesity. Subsequently, however, it was found that most obese people have relatively high levels of circulating leptin (17), and, while augmenting those levels pharmacologically has some effect on fat mass, the very limited clinical trial information thus far in the public domain suggests that these effects are neither dramatic nor consistent (18). This may relate to the possibility of a rather ill-defined state of leptin resistance existing in most obese humans, or perhaps more plausibly, to the evolution of leptin primarily to signal transitions between states of starvation and nutritional adequacy (19). Taking this latter view, it is not surprising that leptin therapy appears to be most dramatically effective in states where circulating leptin levels are markedly and inappropriately low for the true levels of energy stores. Thus, in congenital leptin deficiency, where
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