{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:38:54Z","timestamp":1790786334234,"version":"4.1.0"},"reference-count":83,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Special Fund of the Tianjin Sports Bureau Scientific Research Project","award":["24SK09"],"award-info":[{"award-number":["24SK09"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Resting myokine abundance cannot distinguish adaptive signaling from compensation, tissue injury, altered receptor availability, or non-muscle contribution. We conducted a targeted narrative review of PubMed\/MEDLINE, Embase, Web of Science Core Collection, and Scopus through 30 June 2026 to examine ciliary neurotrophic factor (CNTF), cardiotrophin-like cytokine factor 1 (CLCF1), and muscle metabolism across basal, insulin-stimulated, exercise, recovery, and training states. CNTF has the better-established CNTFR\u03b1\u2013LIFR\u2013gp130 receptor model, and pharmacological studies link it to AMPK activation, glucose uptake, ceramide handling, and insulin responsiveness. CLCF1 depends partly on CRLF1-associated extracellular availability, whereas its receptor usage and tissue source in skeletal muscle remain incompletely resolved. One recent study provides important preclinical and exploratory human evidence for exercise-responsive CLCF1, but direct human studies pairing CNTF\/CLCF1 kinetics with muscle metabolomics or isotope-resolved flux are lacking. We, therefore, present neurotrophic secretory flexibility as a testable, hypothesis-generating construct rather than a validated biological system or biomarker. Its minimum evaluation requires synchronized measurements of extracellular ligand, receptor-proximal signaling, and metabolic output within the same physiological challenge. Targeted and untargeted metabolomics, lipidomics, quality-controlled annotation, paired tissue and plasma sampling, and stable isotope tracing can determine whether putative coupling is reproducible, muscle-relevant, and altered by aging.<\/jats:p>","DOI":"10.3390\/metabo16080562","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:24:53Z","timestamp":1786353893000},"page":"562","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Stimulus-Resolved Framework for Investigating Putative Neurotrophic Secretome\u2013Metabolome Coupling in Aging Skeletal Muscle: CNTF and CLCF1 as Non-Equivalent Nodes"],"prefix":"10.3390","volume":"16","author":[{"given":"Fei","family":"Tong","sequence":"first","affiliation":[{"name":"College of Physical Education and Health, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5469-9800","authenticated-orcid":false,"given":"Yirui","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Public Health and Health Sciences, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxin","family":"Gui","sequence":"additional","affiliation":[{"name":"School of Public Health and Health Sciences, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aowei","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health and Health Sciences, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health and Health Sciences, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusen","family":"Pei","sequence":"additional","affiliation":[{"name":"School of Public Health and Health Sciences, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zimu","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7812-7786","authenticated-orcid":false,"given":"Mengyang","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health and Health Sciences, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1210\/endrev\/bnaa016","article-title":"Muscle-Organ Crosstalk: The Emerging Roles of Myokines","volume":"41","author":"Severinsen","year":"2020","journal-title":"Endocr. 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