Hypocretin/orexin- and melanin-concentrating hormone-expressing cells form distinct populations in the rodent lateral hypothalamus: relationship to the neuropeptide Y and agouti gene-related protein systems

J Comp Neurol. 1998 Dec 28;402(4):460-74.


Cells in the lateral hypothalamus and in the arcuate nucleus play prominent roles in the central control of food intake; however, a neurochemical link connecting these potential components of a hypothalamic circuitry regulating energy metabolism remains to be established. In the present study, the topographical relationship between cells expressing mRNAs encoding melanin-concentrating hormone and the newly discovered neuropeptide family hypocretins/orexins was studied in the rat and mouse lateral hypothalamus by using double-labeling in situ hybridization. Cells expressing the two mRNAs formed completely distinct populations, with hypocretin/orexin cells located primarily perifornically and in the magnocellular lateral hypothalamic nucleus; melanin-concentrating hormone cells extended in a wider area both laterally and periventricularly and appeared to partly surround the hypocretin/orexin population. In the arcuate nucleus, cells expressing neuropeptide Y and agouti gene-related protein were studied by routine fluorescence and/or confocal microscopy immunohistochemistry. Double staining demonstrated that a large proportion of the neuropeptide Y-positive cell bodies in this nucleus also contained agouti gene-related protein-like immunoreactivity. Moreover, these two peptides also coexisted in nerve terminals surrounding and in close relationship to perikarya and processes of both hypocretin/orexin- and melanin-concentrating hormone-immunoreactive cells in the lateral hypothalamus, whereby the former appeared to receive a more dense innervation. These results thus provide evidence for an arcuate-lateral hypothalamic neuropeptide Y/agouti gene-related protein pathway. Furthermore, the results implicate hypocretin/orexin and melanin-concentrating hormone-expressing cells as downstream targets in neuropeptide Y-induced feeding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agouti-Related Protein
  • Animals
  • Hypothalamic Area, Lateral / cytology*
  • Hypothalamic Area, Lateral / metabolism
  • Hypothalamic Hormones / metabolism*
  • Immunohistochemistry
  • In Situ Hybridization
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Melanins / metabolism*
  • Mice
  • Neuropeptide Y / metabolism
  • Neuropeptides / metabolism*
  • Pituitary Hormones / metabolism*
  • Proteins / metabolism
  • Rats
  • Rats, Sprague-Dawley


  • Agouti-Related Protein
  • Hypothalamic Hormones
  • Intercellular Signaling Peptides and Proteins
  • Melanins
  • Neuropeptide Y
  • Neuropeptides
  • Pituitary Hormones
  • Proteins
  • melanin-concentrating hormone