Trophic Action of Leptin on Hypothalamic Neurons That Regulate Feeding

• Published in: Science (American Association for the Advancement of Science) 2004-04, Vol.304 (5667), p.108-110
• Main Authors: Bouret, Sebastien G., Draper, Shin J., Simerly, Richard B.
• Format: Article
• Language: English
• Subjects: Adults; Agouti-Related Protein; alpha-MSH - analysis; Animals; Animals, Newborn; Arcuate Nucleus of Hypothalamus - cytology; Arcuate Nucleus of Hypothalamus - growth & development; Arcuate Nucleus of Hypothalamus - physiology; Axons - physiology; Biological and medical sciences; Brain; Carbocyanines; Chemical properties; Critical periods; Culture Techniques; Dorsomedial Hypothalamic Nucleus - cytology; Dorsomedial Hypothalamic Nucleus - growth & development; Dorsomedial Hypothalamic Nucleus - physiology; Eating; Eating (Physiology); Feeding Behavior; Feeding. Feeding behavior; Food intake; Fundamental and applied biological sciences. Psychology; Hormones; Hypothalamic Area, Lateral - cytology; Hypothalamic Area, Lateral - growth & development; Hypothalamic Area, Lateral - physiology; Hypothalamus; Hypothalamus - cytology; Hypothalamus - growth & development; Hypothalamus - physiology; Innervation; Intercellular Signaling Peptides and Proteins; Leptin; Leptin - deficiency; Leptin - genetics; Leptin - pharmacology; Leptin - physiology; Mice; Mice, Inbred C57BL; Mice, Obese; Neonates; Nerve Fibers - physiology; Neurites; Neurites - physiology; Neurology; Neurons; Neurons - physiology; Neuroscience; Nutrition; Obesity; Paraventricular Hypothalamic Nucleus - cytology; Paraventricular Hypothalamic Nucleus - growth & development; Paraventricular Hypothalamic Nucleus - physiology; Physiological aspects; Proteins - analysis; Recombinant Proteins - pharmacology; Rodents; Signal Transduction; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1095004

In adult mammals, the adipocyte-derived hormone leptin acts on the brain to reduce food intake by regulating the activity of neurons in the arcuate nucleus of the hypothalamus (ARH). Here, we report that neural projection pathways from the ARH are permanently disrupted in leptin-deficient ($Lep^{ob}/Lep^{ob}$) mice and leptin treatment in adulthood does not reverse these neuroanatomical defects. However, treatment of$Lep^{ob}/Lep^{ob}$neonates with exogenous leptin rescues the development of ARH projections, and leptin promotes neurite outgrowth from ARH neurons in vitro. These results suggest that leptin plays a neurotrophic role during the development of the hypothalamus and that this activity is restricted to a neonatal critical period that precedes leptin's acute regulation of food intake in adults.