Trophic action of leptin on hypothalamic neurons that regulate feeding.
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 (Lepob/Lepob) mice and leptin treatment in adulthood does not reverse these neuroanatomical defects. However, treatment of Lepob/Lepob 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.
Bouret
Sebastien G
SG
Division of Neuroscience, Oregon National Primate Research Center and Oregon Health and Science University, Beaverton, OR 97006, USA.
Draper
Shin J
SJ
Simerly
Richard B
RB
D054369:Agouti-Related Protein; D000818:Animals; D000831:Animals, Newborn; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D001369:Axons / Q000502:physiology*; D002232:Carbocyanines; D046508:Culture Techniques; D004302:Dorsomedial Hypothalamic Nucleus / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D004435:Eating; D005247:Feeding Behavior; D007026:Hypothalamic Area, Lateral / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D007031:Hypothalamus / Q000166:cytology / Q000254:growth & development* / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009412:Nerve Fibers / Q000502:physiology; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D011506:Proteins / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D000521:alpha-MSH / Q000032:analysis
D054369:Agouti-Related Protein; D002232:Carbocyanines; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D011506:Proteins; D011994:Recombinant Proteins; C024286:3,3'-dioctadecylindocarbocyanine; D000521:alpha-MSH