University of Oulu

Mäkelä, K. A., Karhu, T., Jurado Acosta, A., Vakkuri, O., Leppäluoto, J., & Herzig, K.-H. (2018). Plasma Orexin-A Levels Do Not Undergo Circadian Rhythm in Young Healthy Male Subjects. Frontiers in Endocrinology, 9.

Plasma orexin-A levels do not undergo circadian rhythm in young healthy male subjects

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Author: Mäkelä, Kari A.1; Karhu, Toni1,2; Jurado Acosta, Alicia1;
Organizations: 1Research Unit of Biomedicine, Physiology, University of Oulu, Oulu, Finland
2Biocenter Oulu, University of Oulu, Oulu, Finland
3Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland
4Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1 MB)
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Language: English
Published: Frontiers Media, 2018
Publish Date: 2019-07-19


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.

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Series: Frontiers in endocrinology
ISSN: 1664-2392
ISSN-E: 1664-2392
ISSN-L: 1664-2392
Volume: 9
Article number: 710
DOI: 10.3389/fendo.2018.00710
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: We would like to thank Ms. Meeri Kröger and Mrs. Helka Koisti for their excellent technical assistance. We would also like to thank Dr. Dominique Gagnon, Ph.D., for his help with language revision. This study was supported by the Academy of Finland (108478, 110525, 214891, 214890, 215917, 216823, 129568, 217330, 217804, 218035).
Academy of Finland Grant Number: 129568
Detailed Information: 129568 (Academy of Finland Funding decision)
218035 (Academy of Finland Funding decision)
Copyright information: © 2018 Mäkelä, Karhu, Jurado Acosta, Vakkuri, Leppäluoto and Herzig. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.