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Minireview: Leptin and Development of Hypothalamic Feeding Circuits

Oregon National Primate Research Center, Division of Neuroscience and Oregon Health and Science University, Beaverton, Oregon 97006

Address all correspondence and requests for reprints to: Dr. Sebastien G. Bouret, Oregon National Primate Research Center, Division of Neuroscience and Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, Oregon 97006.

The arcuate nucleus of the hypothalamus (ARH) is a critical component of the forebrain pathways that regulate energy homeostasis, and it plays a particularly important role in relaying leptin signal to other part of the hypothalamus. However, until recently, little was known about the development of these critical pathways. Recent work investigating the development of leptin-sensitive hypothalamic pathways suggests possible developmental mechanisms that may contribute to obesity later in life. Anatomic findings indicate that ARH circuits are structurally and functionally immature until the third week of postnatal life in mice. Recent data also suggest that leptin is required for normal development of ARH pathways and that this developmental activity of leptin is restricted to a neonatal window of maximum sensitivity that corresponds to a period of elevated leptin secretion. Thus, leptin may function to organize formation of hypothalamic circuitry in much the same way that sex steroids act on sexually dimorphic circuits. Perturbations in perinatal nutrition that alter leptin levels may, therefore, have enduring consequences for the formation and function of circuits regulating food intake and body weight.

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