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Orexin synthesis and response in the gut
1Department of Physiology and Pharmacology, State University of New York, Health Science Center at Brooklyn, 11203, USA. akirchgessner@netmail.hscbklyn.edu
Neuron
|January 7, 2000
Summary
Orexin (hypocretin) neurons are found in the gut, not just the brain. These gut orexin cells respond to fasting and influence gut function, suggesting a key role in energy balance regulation.
Area of Science:
- Neuroendocrinology
- Gastroenterology
- Metabolism
Background:
- Orexin (hypocretin) is a neuropeptide primarily known for its role in regulating energy balance and arousal within the central nervous system (CNS).
- Orexin-producing neurons were previously thought to be exclusively located in the lateral hypothalamic (LH) area of the brain.
Purpose of the Study:
- To investigate the presence and function of orexin-like signaling within the gastrointestinal tract.
- To determine if gut orexin neurons are responsive to nutritional status and influence gut physiology.
Main Methods:
- Immunohistochemistry to detect orexin-like immunoreactivity and leptin receptors in gut neurons.
- Electrophysiological recordings to assess the function of orexin receptors on secretomotor neurons.
- Western blotting to measure phosphorylated cAMP response element-binding protein (pCREB) levels in orexin-immunoreactive neurons.
Main Results:
- A subset of neurons in the guinea pig gut, co-expressing leptin receptors, exhibited orexin-like immunoreactivity and functional orexin receptors.
- Orexin demonstrated an excitatory effect on secretomotor neurons in the submucosal plexus, leading to increased gut motility.
- Fasting induced an upregulation of pCREB in gut orexin-immunoreactive neurons, indicating a functional response to nutritional state.
Conclusions:
- Orexin signaling is present and functional within the gastrointestinal tract.
- Gut orexin neurons are responsive to fasting and modulate gut functions like secretion and motility.
- These findings suggest that orexin in the gut plays a significant role in regulating energy homeostasis, potentially extending beyond its known CNS functions.