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World J Gastroenterol. Nov 28, 2021; 27(44): 7582-7596
Published online Nov 28, 2021. doi: 10.3748/wjg.v27.i44.7582
Orexins: A promising target to digestive cancers, inflammation, obesity and metabolism dysfunctions
Alain Couvineau, Thierry Voisin, Pascal Nicole, Valerie Gratio, Anne Blais
Alain Couvineau, Thierry Voisin, Pascal Nicole, Valerie Gratio, INSERM UMR1149/Inflammation Research Center, Team “From inflammation to cancer in digestive diseases” labeled by “la Ligue Nationale contre le Cancer”, University of Paris, DHU UNITY, Paris 75018, France
Anne Blais, UMR PNCA, AgroParisTech, INRA, Université Paris-Saclay, Paris 75005, France
Author contributions: Couvineau A, Voisin T, Blais A have equally contributed in writing of the manuscript; Couvineau A, Voisin T, Nicole P, Gratio V and Blais A have read and approved the final version of manuscript.
Supported by INSERM U1149/The Inflammation Research Center, Inserm Transfert, The Institut National du Cancer, No. 2013-213; Ligue Nationale Contre le Cancer, No. R16020HH, GB/MA/CD/EP-12062; and AgroParisTech (INRAE and Université Paris-Saclay).
Conflict-of-interest statement: Authors don’t have any conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Alain Couvineau, PhD, Academic Research, INSERM UMR1149 /Inflammation Research Center (CRI), Team “From inflammation to cancer in digestive diseases” labeled by “la Ligue Nationale contre le Cancer”, University of Paris, DHU Unity, 16 rue Henri Huchard, Paris 75018, France. alain.couvineau@inserm.fr
Received: April 20, 2021
Peer-review started: April 20, 2021
First decision: June 13, 2021
Revised: June 22, 2021
Accepted: November 15, 2021
Article in press: November 15, 2021
Published online: November 28, 2021
Processing time: 218 Days and 18.9 Hours
Abstract

Hypothalamic neuropeptides named hypocretin/orexins which were identified in 1998 regulate critical functions such as wakefulness in the central nervous system. These past 20 years had revealed that orexins/receptors system was also present in the peripheral nervous system where they participated to the regulation of multiple functions including blood pressure regulation, intestinal motility, hormone secretion, lipolyze and reproduction functions. Associated to these peripheral functions, it was found that orexins and their receptors were involved in various diseases such as acute/chronic inflammation, metabolic syndrome and cancers. The present review suggests that orexins or the orexin neural circuitry represent potential therapeutic targets for the treatment of multiple pathologies related to inflammation including intestinal bowel disease, multiple sclerosis and septic shock, obesity and digestive cancers.

Keywords: Orexin; Neuropeptide; G-protein coupled receptor superfamily; Inflammation; Metabolic syndrome; Cancer

Core Tip: Twenty years ago, hypothalamic orexin peptides hypocretin-1/orexin-A and hypocretin-2/orexin-B) and their receptors were identified. They belong to the G-protein coupled receptor superfamily. Orexins and their receptors were involved in the regulation of many functions in the central nervous system: the regulation of wakefulness, drug addictions, food consumption, energy homeostasis and stress. However, various biological effects have been also identified in the peripheral nervous system including endocrine and cardiovascular functions. Orexins/orexin receptors have been shown to play a major role in various peripheral diseases encompassing chronic inflammation and cancers. The present review focuses on the impact of orexin exogenous administration, in various pathophysiological conditions including digestive cancers, intestinal bowel disease, septic shock, multiple sclerosis and metabolic syndrome.