The known and unknown of leptin in pregnancy

Leptin, which was identified originally as an adipocyte-derived protein, was regarded for years as an exclusive regulator of satiety and energy homeostasis. A role for leptin in pregnancy was later suggested by the findings that plasma levels during gestation are greater than in nongravid individuals and that leptin is synthesized within the fetoplacental unit. Observational studies have established that leptin production is dysregulated in several pathologic stages of pregnancy in association with alterations of fetal growth. For example, an overproduction of leptin by the placenta in pregnancy with diabetes mellitus or hypertension is associated with maternal hyperleptinemia. Evidence is also accumulating that umbilical leptin levels can be viewed as a biomarker of fetal adiposity. Ten years after its discovery as a hormone, we review the known and unknowns of leptin in pregnancy with particular emphasis on its functions in health and disease. We aim to demonstrate that studies of leptin in pregnancy largely have contributed to insight into the mechanisms of leptin action, both as a hormone and as a cytokine.