Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area

Neuron. 1999 Aug;23(4):775-86. doi: 10.1016/s0896-6273(01)80035-0.


Recent studies have reinforced the view that the lateral hypothalamic area (LHA) regulates food intake and body weight. We identified leptin-sensitive neurons in the arcuate nucleus of the hypothalamus (Arc) that innervate the LHA using retrograde tracing with leptin administration. We found that retrogradely labeled cells in the Arc contained neuropeptide Y (NPY) mRNA or proopiomelanocortin (POMC) mRNA. Following leptin administration, NPY cells in the Arc did not express Fos but expressed suppressor of cytokine signaling-3 (SOCS-3) mRNA. In contrast, leptin induced both Fos and SOCS-3 expression in POMC neurons, many of which also innervated the LHA. These findings suggest that leptin directly and differentially engages NPY and POMC neurons that project to the LHA, linking circulating leptin and neurons that regulate feeding behavior and body weight homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arcuate Nucleus of Hypothalamus / cytology
  • Arcuate Nucleus of Hypothalamus / physiology*
  • Body Weight / physiology
  • Cell Count
  • Eating / physiology
  • Homeostasis / physiology
  • Hypothalamic Area, Lateral / cytology
  • Hypothalamic Area, Lateral / physiology*
  • Immunohistochemistry
  • In Situ Hybridization
  • Leptin
  • Male
  • Neural Pathways / cytology
  • Neural Pathways / physiology
  • Neurons / physiology*
  • Neuropeptide Y / physiology*
  • Pro-Opiomelanocortin / physiology*
  • Protein Biosynthesis
  • Proteins / physiology*
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Proto-Oncogene Proteins c-fos / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Repressor Proteins*
  • Signal Transduction / physiology
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Transcription Factors*


  • Leptin
  • Neuropeptide Y
  • Proteins
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Repressor Proteins
  • Socs3 protein, rat
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Transcription Factors
  • Pro-Opiomelanocortin