Neural site of leptin influence on neuropeptide Y signaling pathways altering feeding and uncoupling protein

Catherine M Kotz, Jacqueline E. Briggs, James D. Pomonis, Martha K. Grace, Allen S Levine, Charles J Billington

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50 Scopus citations


Inhibition of a signal that produces positive energy balance involving neuropeptide Y (NPY) projection from arcuate nucleus (Arc; site of NPY synthesis) to paraventricular nucleus (PVN; site of NPY release) is one potential mechanism of leptin action. NPY in the PVN increases feeding and decreases uncoupling protein (UCP) activity in brown fat, whereas leptin decreases NPY biosynthesis in the Arc, which presumably decreases PVN NPY. It is hypothesized that decreased NPY activity is necessary for the satiety and thermogenic effects of leptin. To test this, we first determined the effect of leptin on feeding in two paradigms: satiated rats and food-deprived rats. Leptin was effective in decreasing feeding in the satiated rats but ineffective in the food-deprived rats. Next, we determined that leptin decreases NPY and increases UCP gene expression. Finally, we injected leptin intracerebroventricularly before specific PVN NPY microinjection. We found that repletion of NPY in PVN by specific NPY microinjection reverses the feeding-inhibitory and thermogenic effects of centrally administered leptin, the first functional evidence indicating that leptin acts on the Arc-PVN feeding-regulatory pathway.

Original languageEnglish (US)
Pages (from-to)R478-R484
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number2 44-2
StatePublished - 1998


  • Arcuate nucleus
  • Brown adipose tissue
  • Food intake
  • Gene expression
  • Paraventricular nucleus


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