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Cited by 119Sleep and Wakefulness ResearchRegulation of Appetite and ObesityNeuroscience of respiration and sleep

Fasting Activates the Nonhuman Primate Hypocretin (Orexin) System and Its Postsynaptic Targets

Diano, Sabrina, Horvath, Balazs, Urbanski, Henryk F., Sotonyi, Peter, Horvath, Tamas L.·2003·Endocrinology
DOI 10.1210/en.2003-0274
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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.

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  • Orexin neurons can integrate metabolic state signals such as leptin, insulin, and glucose.

    “Orexin neurons can integrate various metabolic state signals such as leptin, insulin, and glucose”

    From Food reward, hyperphagia, and obesity (2011) · cites this paper as [51]

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Authors
Diano, S., Horvath, B., Urbanski, H. F., Sotonyi, P., & Horvath, T. L.
Affiliations
  • Yale University (US)
  • Department of Neurobiology (B.H., T.L.H.), Yale University School of Medicine, New Haven, Connecticut, 06520
  • Oregon National Primate Research Center (US)
  • Department of Anatomy and Histology (P.S.), Szent Istvan University, School of Veterinary Medicine, Budapest, Hungary, 1071
  • Department of Obstetrics and Gynecology (S.D., T.L.H.), Yale University School of Medicine, New Haven, Connecticut, 06520
ORCID
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2003-09-01
Volume
144
Issue
9
Pages
3774-3778
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/en.2003-0274
OpenAlex
W1983036167
Cited by
119
References
20
Citations by year
2026: 3 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 1 · 2021: 7 · 2020: 5 · 2019: 5 · 2018: 5 · 2017: 9 · 2016: 3 · 2015: 5 · 2014: 6 · 2013: 4 · 2012: 7
FWCI
4.23
Type
journal article
Language
en
Open access
closed
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Yale University
  • National Institutes of Health (1s10rr011451-01)
  • Raymond and Beverly Sackler Institute for Biological, Physical and Engineering Sciences, Yale University
  • National Center for Research Resources (RR-11451, R01RR014451)
  • Yale Liver Center
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
Keywords
orexin, fasting, hypothalamus, lateral hypothalamus, dorsomedial hypothalamus, leptin, c-fos, neuropeptide Y, arcuate nucleus, non-human primates, homeostasis, synaptic innervation, metabolic regulation
MeSH terms
Orexins, Animals, Axons, Carrier Proteins, Chlorocebus aethiops, Eating, Fasting, Female, Hypothalamus, Neuropeptides, Proto-Oncogene Proteins c-fos, Intracellular Signaling Peptides and Proteins

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