Orexins and orexin receptors: implication in feeding behavior

Area of Science:

• Neuroscience
• Endocrinology
• Physiology

Background:

• Orexins (also known as hypocretins) are neuropeptides discovered as endogenous ligands for an orphan G protein-coupled receptor.
• Their distribution in the lateral hypothalamic area, a region associated with feeding behavior, initially guided research into their functions.

Purpose of the Study:

• To investigate the role of orexins in regulating feeding behavior.
• To explore the neuroanatomical basis for orexin regulation of feeding by examining their connections with other hypothalamic nuclei.
• To understand the broader physiological roles of orexins beyond feeding, given their widespread brain distribution.

Main Methods:

• Administration of orexin-A intracerebroventricularly during the early light phase to observe effects on food consumption.
• Analysis of orexin mRNA expression levels in response to fasting.
• Examination of the innervation of orexin neurons in the lateral hypothalamus by peptidergic fibers from the arcuate nucleus, including those from NPY-, AgRP-, and a-MSH-expressing cells.

Main Results:

• Intracerebroventricular administration of orexin-A stimulated food consumption in the early light phase.
• Orexin mRNA expression was found to be up-regulated by fasting, indicating regulation by nutritional status.
• Orexin neurons receive input from leptin-responsive neurons in the arcuate nucleus, suggesting a link between peripheral metabolic cues and central regulatory pathways for feeding.

Conclusions:

• Orexins play a significant role in regulating feeding behavior, with their expression modulated by nutritional status.
• The neuroanatomical connections of orexin neurons provide a basis for integrating metabolic information and regulating feeding.
• Orexins have diverse physiological roles, including the regulation of drinking behavior, neuroendocrine function, and the sleep-wake cycle, due to their widespread projections throughout the brain.