Fasting activates the nonhuman primate hypocretin (orexin) system and its postsynaptic targets

Sabrina Diano, Balazs Horvath, Henryk F. Urbanski, P. Sótonyi, Tamas L. Horvath

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

In rodents, hypocretin (HCRT, also called orexin) influences a variety of endocrine, autonomic, and metabolic functions. The present study was undertaken to determine whether the HCRT-producing circuit is involved in the hypothalamic regulation of homeostasis in primates as well. We studied female monkeys (Cercopithecus aethiops) that were either fed or fasted for 24 h. Immunocytochemistry revealed HCRT-producing perikarya exclusively in the lateral hypothalamus-perifornical region and dorsomedial hypothalamus of the monkey brain. HCRT axons and axon terminals were present in different parts of the hypothalamus and adjacent forebrain and thalamic nuclei. The 24-h fast resulted in an approximately 50% decline in circulating leptin levels and significantly elevated c-fos expression in the perifornical region; in the dorsomedial, ventromedial, and arcuate nuclei; and in the medial preoptic area. In the dorsomedial nucleus and perifornical region of fasted monkeys, three times more HCRT-neurons expressed nuclear c-fos than those of the normally fed controls. Neurons in different parts of the hypothalamus and basal forebrain that expressed c-fos, but did not contain HCRT, were targets of HCRT-immunopositive boutons establishing asymmetric synapses. In the arcuate nucleus, subsets of these HCRT-targeted c-fos-expressing cells contained neuropeptide Y. The present study provides the first experimental evidence to implicate HCRT in the hypothalamic regulation of homeostasis in primates. The fact that these lateral hypothalamic cells have leptin receptors and can be activated by a metabolic challenge and that they innervate diverse brain regions indicates that the HCRT system may be a key integrator of environmental cues in their regulation of diverse brain activity.

Original languageEnglish
Pages (from-to)3774-3778
Number of pages5
JournalEndocrinology
Volume144
Issue number9
DOIs
Publication statusPublished - Sep 1 2003

Fingerprint

Primates
Hypothalamus
Haplorhini
Mediodorsal Thalamic Nucleus
Fasting
Arcuate Nucleus of Hypothalamus
Brain
Homeostasis
Lateral Hypothalamic Area
Neurons
Leptin Receptors
Cercopithecus aethiops
Thalamic Nuclei
Preoptic Area
Neuropeptide Y
Presynaptic Terminals
Prosencephalon
Leptin
Synapses
Cues

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Fasting activates the nonhuman primate hypocretin (orexin) system and its postsynaptic targets. / Diano, Sabrina; Horvath, Balazs; Urbanski, Henryk F.; Sótonyi, P.; Horvath, Tamas L.

In: Endocrinology, Vol. 144, No. 9, 01.09.2003, p. 3774-3778.

Research output: Contribution to journalArticle

Diano, Sabrina ; Horvath, Balazs ; Urbanski, Henryk F. ; Sótonyi, P. ; Horvath, Tamas L. / Fasting activates the nonhuman primate hypocretin (orexin) system and its postsynaptic targets. In: Endocrinology. 2003 ; Vol. 144, No. 9. pp. 3774-3778.
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