Several discoveries over the past 10 years have created opportunities for prevention and/or treatment, including discoveries of new genes, molecules, and regulatory pathways. Central, in my opinion, may prove to be developments in the field encompassed by the question: How does negative energy balance lead to neuroendocrine abnormalities? Recent work, mainly from our laboratory, has demonstrated that levels of an adi-pocyte-secreted hormone, circulating levels of which reflect the amount of energy stored in fat, i.e. leptin, fall in response to negative energy balance and this fall can lead to the neuroendocrine dysfunction that has traditionally been associated with energy, and thus leptin, deficiency states, such as anorexia nervosa and exercise-induced or hypothalamic amenorrhea. Importantly, exogenous administration of leptin, in replacement doses, can correct these neuroendocrine abnormalities in these leptin deficiency states. These novel advances, discussed in the relevant chapters of this book, open new and exciting avenues for diagnosing and treating these conditions in the future. Whether additional factors may also play a role or modify the effects of leptin administration remains to be seen. It also remains to be seen whether falling leptin levels in response to caloric/energy deprivation in obese persons who diet to lose weight may also be responsible for their neuroendocrine changes, which, in turn, tend to defend the original body weight and to make the obese person regain any weight lost in response to dieting.
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