{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:27:05Z","timestamp":1785403625629,"version":"3.56.0"},"reference-count":70,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,4,29]],"date-time":"2019-04-29T00:00:00Z","timestamp":1556496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"University of Reading Research Endowment Trust Fund"},{"name":"Otsuka Pharmaceuticals"},{"name":"GW Research Ltd"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Muscle wasting, anorexia, and metabolic dysregulation are common side\u2010effects of cytotoxic chemotherapy, having a dose\u2010limiting effect on treatment efficacy, and compromising quality of life and mortality. Extracts of Cannabis sativa, and analogues of the major phytocannabinoid \u03949\u2010tetrahydrocannabinol, have been used to ameliorate chemotherapy\u2010induced appetite loss and nausea for decades. However, psychoactive side\u2010effects limit their clinical utility, and they have little efficacy against weight loss. We recently established that the non\u2010psychoactive phytocannabinoid cannabigerol (CBG) stimulates appetite in healthy rats, without neuromotor side\u2010effects. The present study assessed whether CBG attenuates anorexia and\/or other cachectic effects induced by the broad\u2010spectrum chemotherapy agent cisplatin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An acute cachectic phenotype was induced in adult male Lister\u2010hooded rats by 6 mg\/kg (i.p.) cisplatin. In total 66 rats were randomly allocated to groups receiving vehicle only, cisplatin only, or cisplatin and 60 or 120 mg\/kg CBG (po, b.i.d.). Feeding behavior, bodyweight and locomotor activity were recorded for 72 hours, at which point rats were sacrificed for post\u2010mortem analyses. Myofibre atrophy, protein synthesis and autophagy dysregulation were assessed in skeletal muscle, plasma metabolic profiles were obtained by untargeted 1H\u2010NMR metabonomics, and levels of endocannabinoid\u2010like lipoamines quantified in plasma and hypothalami by targeted HPLC\u2010MS\/MS lipidomics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CBG (120 mg\/kg) modestly increased food intake, predominantly at 36\u201060hrs (p&lt;0.05), and robustly attenuated cisplatin\u2010induced weight loss from 6.3% to 2.6% at 72hrs (p&lt;0.01). Cisplatin\u2010induced skeletal muscle atrophy was associated with elevated plasma corticosterone (3.7 vs 13.1ng\/ml, p&lt;0.01), observed selectively in MHC type IIx (p&lt;0.05) and IIb (p&lt;0.0005) fibres, and was reversed by pharmacological rescue of dysregulated Akt\/S6\u2010mediated protein synthesis and autophagy processes. Plasma metabonomic analysis revealed cisplatin administration produced a wide\u2010ranging aberrant metabolic phenotype (Q2\u0176=0.5380, p=0.001), involving alterations to glucose, amino acid, choline and lipid metabolism, citrate cycle, gut microbiome function, and nephrotoxicity, which were partially normalized by CBG treatment (Q2\u0176=0.2345, p=0.01). Lipidomic analysis of hypothalami and plasma revealed extensive cisplatin\u2010induced dysregulation of central and peripheral lipoamines (29\/79 and 11\/26 screened, respectively), including reversible elevations in systemic N\u2010acyl glycine concentrations which were negatively associated with the anti\u2010cachectic effects of CBG treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Endocannabinoid\u2010like lipoamines may have hitherto unrecognized roles in the metabolic side\u2010effects associated with chemotherapy, with the N\u2010acyl glycine subfamily in particular identified as a potential therapeutic target and\/or biomarker of anabolic interventions. CBG\u2010based treatments may represent a novel therapeutic option for chemotherapy\u2010induced cachexia, warranting investigation in tumour\u2010bearing cachexia models.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12426","type":"journal-article","created":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T01:39:23Z","timestamp":1556674763000},"page":"844-859","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Chemotherapy\u2010induced cachexia dysregulates hypothalamic and systemic lipoamines and is attenuated by cannabigerol"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4360-2648","authenticated-orcid":false,"given":"Daniel I.","family":"Brierley","sequence":"first","affiliation":[{"name":"School of Psychology and Clinical Language Sciences University of Reading  Berkshire UK"},{"name":"School of Pharmacy University of Reading  Berkshire UK"},{"name":"Department of 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A.D.","family":"Mellows","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of Reading  Berkshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather B.","family":"Bradshaw","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences Indiana University  Bloomington IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R.","family":"Swann","sequence":"additional","affiliation":[{"name":"Division of Computational and Systems Medicine Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketan","family":"Patel","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of Reading  Berkshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J.","family":"Whalley","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Reading  Berkshire 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