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

Area of Science:

• Neuroscience
• Endocrinology
• Metabolism

Background:

• Hypocretin (HCRT), also known as orexin, is a neuropeptide involved in regulating endocrine, autonomic, and metabolic functions in rodents.
• The role of the HCRT-producing circuit in hypothalamic homeostasis regulation in primates remains largely unexplored.

Purpose of the Study:

• To investigate the involvement of the HCRT-producing circuit in hypothalamic homeostasis regulation in primates.
• To determine the impact of metabolic challenges on HCRT neuron activity and their targets in the primate brain.

Main Methods:

• Immunocytochemistry was used to identify HCRT-producing neurons and their projections in the hypothalamus of female monkeys (Cercopithecus aethiops).
• C-fos expression was analyzed in fed and 24-h fasted monkeys to assess neuronal activation.
• Leptin levels were measured to evaluate the metabolic state.

Main Results:

• HCRT neurons were localized to the lateral hypothalamus-perifornical region and dorsomedial hypothalamus.
• Fasting significantly increased c-fos expression in HCRT neurons and other hypothalamic nuclei, including the arcuate nucleus.
• HCRT-immunopositive boutons synapsed with c-fos-expressing neurons, some containing neuropeptide Y, indicating HCRT's role in regulating appetite pathways.

Conclusions:

• This study provides the first experimental evidence implicating HCRT in hypothalamic homeostasis regulation in primates.
• Activated HCRT neurons, responsive to metabolic cues like leptin, innervate diverse brain regions, suggesting a key role in integrating environmental signals.
• The HCRT system is crucial for regulating diverse brain activities related to homeostasis in primates.