Figure 1.

The importance of the perinatal leptin surge as a stimulus for hypothalamic development. A: During normal human pregnancy, fetal leptin levels rapidly increase from gestational week 32 to delivery. Mice have a relative delay in adipogenesis and an analogous increase in leptin does not occur until postnatal days 4 to 14. In both species, the physiologic increase in perinatal leptin is critical for normal hypothalamic development. In adulthood, cardiometabolic homeostasis is facilitated by well-tuned appetite regulation and sympathetic tone. B: Perinatal leptin deficiency can occur following intrauterine growth restriction (IUGR) or prematurity in humans, neonatal growth restriction in mice, or exaggerated perinatal glucocorticoid exposure in both species. The attenuated leptin surge increases the risk of hypothalamic hypoplasia and dysregulation with the potential for hypersensitivity to leptin-triggered sympathetic activation in the presence of selective resistance to leptin-mediated anorexia. Individuals with obesity-related hyperleptinemia in the presence of heightened leptin-mediated sympathetic activation are at dramatically increased risk of adult hypertension.