---
title: "Orexin and GLP-1 Regulatory Cycles in Postviral Syndromes: Implications for PASC and ME/CFS"
id: "pubmed-42037238"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42037238"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42037238/"
doi: "10.1210/endrev/bnag009"
published_at: "2026-09-16T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Orexin and GLP-1 Regulatory Cycles in Postviral Syndromes: Implications for PASC and ME/CFS
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42037238
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42037238/)
- **DOI:** [10.1210/endrev/bnag009](https://doi.org/10.1210%2Fendrev%2Fbnag009)
- **Published At:** 2026-09-16T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Postviral syndromes are heterogeneous, multisystem conditions arising after acute viral infections; the COVID-19 pandemic increased cases labeled as postacute sequelae of COVID-19 (**PASC**). - Many PASC cases overlap with myalgic encephalomyelitis/chronic fatigue syndrome (**ME/CFS**), which features severe fatigue, postexertional malaise (PEM), unrefreshing sleep, neurocognitive impairment, and autonomic and immune dysregulation. - **Orexin (OX)** neuropeptides regulate arousal, metabolism, and neuroendocrine functions and may connect stress, immune activation, and metabolic changes seen in postviral syndromes. - Phenotypic similarities between impaired **OX** signaling and core PASC/ME/CFS features (fatigue, sleep disturbance, impaired glucose metabolism, neuropsychiatric symptoms) support a mechanistic link. - The review discusses OX roles in glucose metabolism, hypothalamic-pituitary-adrenal (HPA) axis activity, and systemic homeostasis, highlighting sexually dimorphic expression and function relevant to postviral disease. - **Glucagon-like peptide-1 (GLP-1)** is noted as a metabolic regulator with neuroprotective, anti-inflammatory, vasoprotective, and immunomodulatory properties relevant to postviral syndromes. - Emerging therapeutic strategies include **GLP-1 receptor agonists (GLP-1RAs)** and agents targeting the **OX** system; the review frames these within an integrated neuroendocrine-metabolic model for PASC and ME/CFS. - Keywords emphasized in the source include (pre-)diabetes, COVID-19, GLP-1, PASC, insulin resistance, and orexin. Details on specific clinical trial outcomes or dosing were not reported in the abstract and are not available in the provided source text.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Department of Cardiology, Angiology and Critical Care Medicine, Philipps University Marburg, Marburg 35043, Germany. * 2 State of Hessen postCOVID Coordination Center, Marburg 35043, Germany. * PMID: **42037238** * DOI: [ 10.1210/endrev/bnag009 ](https://doi.org/10.1210/endrev/bnag009) Item in Clipboard Review # Regulatory cycles of orexin and glucagon-Like peptide-1 in postviral syndromes Jana Ruhrländer et al. Endocr Rev. 2026. Show details Display options Display options Format Abstract PubMed PMID Endocr Rev Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Endocr+Rev%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Endocr+Rev%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42037238/) . 2026 Sep 16;47(5):535-564. doi: 10.1210/endrev/bnag009. ### Authors [Jana Ruhrländer](https://pubmed.ncbi.nlm.nih.gov/?term=Ruhrl%C3%A4nder+J&cauthor_id=42037238)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42037238/#short-view-affiliation-1 "Department of Cardiology, Angiology and Critical Care Medicine, Philipps University Marburg, Marburg 35043, Germany.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42037238/#short-view-affiliation-2 "State of Hessen postCOVID Coordination Center, Marburg 35043, Germany."), [Elisabeth Schieffer](https://pubmed.ncbi.nlm.nih.gov/?term=Schieffer+E&cauthor_id=42037238)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42037238/#short-view-affiliation-1 "Department of Cardiology, Angiology and Critical Care Medicine, Philipps University Marburg, Marburg 35043, Germany."), [Bernhard Schieffer](https://pubmed.ncbi.nlm.nih.gov/?term=Schieffer+B&cauthor_id=42037238)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42037238/#short-view-affiliation-1 "Department of Cardiology, Angiology and Critical Care Medicine, Philipps University Marburg, Marburg 35043, Germany.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42037238/#short-view-affiliation-2 "State of Hessen postCOVID Coordination Center, Marburg 35043, Germany.") ### Affiliations * 1 Department of Cardiology, Angiology and Critical Care Medicine, Philipps University Marburg, Marburg 35043, Germany. * 2 State of Hessen postCOVID Coordination Center, Marburg 35043, Germany. * PMID: **42037238** * DOI: [ 10.1210/endrev/bnag009 ](https://doi.org/10.1210/endrev/bnag009) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Postviral syndromes are heterogeneous multisystem diseases without a uniform etiology that occur as a result of acute viral infections. During the COVID-19 pandemic, the number of patients increased dramatically due to infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This is known as postacute sequelae of COVID-19 (PASC), with many cases also meeting the criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), the most severe form of a postviral disease, characterized by severe fatigue, postexertional malaise (PEM), unrefreshing sleep, neurocognitive impairment, and autonomic and immune dysregulation. Orexin (OX) neuropeptides, which regulate arousal, metabolism, and neuroendocrine functions, may serve as a central link among stress, immune activation, and metabolic changes in these syndromes. Notable phenotypic similarities between OX system dysfunction and core features of PASC and ME/CFS, including fatigue, sleep issues, impaired glucose metabolism, and neuropsychiatric symptoms, support a mechanistic model in which impaired OX signaling contributes to postviral endocrine and metabolic dysfunction. This review examines the role of OX in regulating glucose metabolism, HPA axis activity, and systemic homeostasis, with a specific focus on sexually dimorphic expression and function in relation to postviral syndromes. We also highlight the effect of glucagon-like peptide-1 (GLP-1), another key player in metabolism, which also has neuroprotective, anti-inflammatory, vasoprotective, and immunomodulatory effects. We further emphasize emerging therapeutic strategies, such as GLP-1 receptor agonists (GLP-1RAs) and drugs targeting the OX system. Together, these insights provide an integrated framework for understanding and targeting the neuroendocrine-metabolic underpinnings of PASC, ME/CFS, and other postviral syndromes. **Keywords:** (pre-) diabetes; COVID-19; GLP-1; PASC; insulin resistance; orexin. © The Author(s) 2026. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [ Long COVID in pediatrics-epidemiology, diagnosis, and management. ](https://pubmed.ncbi.nlm.nih.gov/38279014/) Toepfner N, Brinkmann F, Augustin S, Stojanov S, Behrends U.Toepfner N, et al.Eur J Pediatr. 2024 Apr;183(4):1543-1553. doi: 10.1007/s00431-023-05360-y. Epub 2024 Jan 27.Eur J Pediatr. 2024.PMID: 38279014Free PMC article.Review. * [ Extracellular vesicle proteomics uncovers energy metabolism, complement system, and endoplasmic reticulum stress response dysregulation postexercise in males with myalgic encephalomyelitis/chronic fatigue syndrome. ](https://pubmed.ncbi.nlm.nih.gov/40465195/) Glass KA, Giloteaux L, Zhang S, Hanson MR.Glass KA, et al.Clin Transl Med. 2025 May;15(5):e70346. doi: 10.1002/ctm2.70346.Clin Transl Med. 2025.PMID: 40465195Free PMC article. * [ Evidence for Peroxisomal Dysfunction and Dysregulation of the CDP-Choline Pathway in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. ](https://pubmed.ncbi.nlm.nih.gov/35043127/) Che X, Brydges CR, Yu Y, Price A, Joshi S, Roy A, Lee B, Barupal DK, Cheng A, Palmer DM, Levine S, Peterson DL, Vernon SD, Bateman L, Hornig M, Montoya JG, Komaroff AL, Fiehn O, Lipkin WI.Che X, et al.medRxiv [Preprint]. 2022 Jan 11:2021.06.14.21258895. doi: 10.1101/2021.06.14.21258895.medRxiv. 2022.Update in: [Int J Mol Sci. 2022 Jul 18;23(14):7906. doi: 10.3390/ijms23147906.](https://pubmed.ncbi.nlm.nih.gov/35887252/)PMID: 35043127Free PMC article.Updated.Preprint. * [ Circadian rhythm disruption in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for the post-acute sequelae of COVID-19. ](https://pubmed.ncbi.nlm.nih.gov/35465246/) McCarthy MJ.McCarthy MJ.Brain Behav Immun Health. 2022 Jan 10;20:100412. doi: 10.1016/j.bbih.2022.100412. eCollection 2022 Mar.Brain Behav Immun Health. 2022.PMID: 35465246Free PMC article. * [ Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC). ](https://pubmed.ncbi.nlm.nih.gov/36947108/) Sherif ZA, Gomez CR, Connors TJ, Henrich TJ, Reeves WB; RECOVER Mechanistic Pathway Task Force.Sherif ZA, et al.Elife. 2023 Mar 22;12:e86002. doi: 10.7554/eLife.86002.Elife. 2023.PMID: 36947108Free PMC article.Review. 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