Leptin regulation of neuroendocrine systems

Rexford S. Ahima, Clifford B. Saper, Jeffrey S. Flier, Joel K. Elmquist

Research output: Contribution to journalArticlepeer-review

656 Scopus citations


The discovery of leptin has enhanced understanding of the interrelationship between adipose energy stores and neuronal circuits in the brain involved in energy balance and regulation of the neuroendocrine axis. Leptin levels are dependent on the status of fat stores as well as changes in energy balance as a result of fasting and overfeeding. Although leptin was initially thought to serve mainly as an anti-satiety hormone, recent studies have shown that it mediates the adaptation to fasting. Furthermore, leptin has been implicated in the regulation of the reproductive, thyroid, growth hormone, and adrenal axes, independent of its role in energy balance. Although it is widely known that leptin acts on hypothalamic neuronal targets to regulate energy balance and neuroendocrine function, the specific neuronal populations mediating leptin action on feeding behavior and autonomic and neuroendocrine function are not well understood. In this review, we have discussed how leptin engages arcuate hypothalamic neurons expressing putative orexigenic peptides, e.g., neuropeptide Y and agouti-regulated peptide, and anorexigenic peptides, e.g., pro-opiomelanocortin (precursor of α-melanocyte-stimulating hormone) and cocaine- and amphetamine-regulated transcript. We show that leptin's effects on energy balance and the neuroendocrine axis are mediated by projections to other hypothalamic nuclei, e.g., paraventricular, lateral, and perifornical areas, as well as other sites in the brainstem, spinal cord, and cortical and subcortical regions. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)263-307
Number of pages45
JournalFrontiers in Neuroendocrinology
Issue number3
StatePublished - Jul 2000


  • Arcuate hypothalamic nucleus
  • Dorsomedial hypothalamic nucleus
  • Feeding
  • OB protein
  • Obesity
  • Ventromedial hypothalamic nucleus

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems


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