Abstract
Orexin-A (OXA) has been originally isolated from a precursor peptide prepro-orexin from the lateral hypothalamus. The orexin system has been attributed to important functions in sleep, arousal and regulation of energy homeostasis. In addition to its high levels in cerebrospinal fluid, OXA is present in blood. However, reported peptide concentrations in plasma vary significantly depending on the method used. Therefore, a specific and sensitive OXA radioimmunoassay (RIA) with solid phase extraction method was developed to determine whether plasma OXA concentrations is affected by acute feeding and/or wake and sleep in young healthy males. Blood samples were collected for 24 h from nine healthy males (aged 20–24 years; BMI 20.7–26.5) every 2 h starting at 11 a.m. Food was served at 12 p.m, 5:30 p.m, 8 p.m and 8 a.m and the sleep time was between 10 p.m and 7 a.m. Plasma samples were analyzed in addition for cortisol and melatonin levels. Blood pressure was monitored through the experimental period. OXA antibody was raised in rabbits. OXA antiserum had only minor cross-reactivity with prepro-orexin precursor (<0.001%), amino-terminal peptide (<0.001%), carboxy-terminal peptide (0.001%), and orexin-B (0.3%) with high sensitivity (0.15 pg/tube). Plasma OXA levels varied between 0.5 and 16 pg/ml in seven subjects and were undetectable (below 0.5 pg/ml) in two subjects. The OXA concentrations did not correlate to feeding nor wake/sleep, whereas cortisol, melatonin and mean arterial blood pressure presented a clear circadian rhythm in each subject. In conclusion, OXA is present in blood in low amounts and its levels do not follow autonomic nor neuroendocrine circadian rhythms. Thereby, studies examining regulatory mechanisms and influences of OXA from blood samples should interpret results very cautiously.
Highlights
Orexin-A and orexin-B, called hypocretins, are peptides which were originally isolated from rat hypothalamus and are derived from the precursor peptide prepro-orexin (PPO) [1]
PPO had reduced REM sleep compared with wild type mice indicating the importance of orexins in regulation of REM sleep and stabilization of arousal [11]
Cerebrospinal fluid (CSF) OXA fluctuates depending on the time of the day with peak concentrations late in the night [3, 9]
Summary
Orexin-A and orexin-B, called hypocretins, are peptides which were originally isolated from rat hypothalamus and are derived from the precursor peptide prepro-orexin (PPO) [1]. Narcoleptic patients with cataplexy have low levels of OXA in their cerebrospinal fluid [6] They have an altered secretion of melatonin with high daytime secretion, suggesting that orexin might have a role in the control of melatonin release [12]. It has been shown that patients with insomnia have significantly elevated plasma OXA levels compared to healthy subjects [13]. Intermittent daily fasting increased plasma OXA levels during fasting hours in healthy male volunteers [20]. It is unknown whether plasma OXA levels correlate to acute feeding and/or wakefulness and sleep in humans
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