{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:02:53Z","timestamp":1791932573105,"version":"4.3.4"},"reference-count":39,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T00:00:00Z","timestamp":1664323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Allen Foundation","award":["grant number 2011.385"],"award-info":[{"award-number":["grant number 2011.385"]}]},{"name":"Australian Rotary Health Scholarship","award":["grant number 2011.385"],"award-info":[{"award-number":["grant number 2011.385"]}]},{"name":"Griffith University","award":["grant number 2011.385"],"award-info":[{"award-number":["grant number 2011.385"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diet-induced obesity (DIO) reduces fatty acid oxidation in skeletal muscle and decreases circulating levels of adiponectin. Endocannabinoid signaling is overactive in obesity, with some effects abated by antagonism of cannabinoid receptor 1 (CB1). This research aimed to determine if treatment with the global CB1 antagonist\/inverse agonist, AM251, in high-fat diet (HFD) fed rats influenced adiponectin signaling in skeletal muscle and a \u201cbrowning\u201d of white adipose tissue (WAT) defined by UCP1 expression levels. Male Sprague Dawley rats consumed an HFD (21% fat) for 9 weeks before receiving daily intraperitoneal injections with vehicle or AM251 (3 mg\/kg) for 6 weeks. mRNA expression of genes involved in metabolic functions were measured in skeletal muscle and adipose tissue, and blood was harvested for the measurement of hormones and cytokines. Muscle citrate synthase activity was also measured. AM251 treatment decreased fat pad weight (epididymal, peri-renal, brown), and plasma levels of leptin, glucagon, ghrelin, and GLP-1, and increased PAI-1 along with a range of pro-inflammatory and anti-inflammatory cytokines; however, AM251 did not alter plasma adiponectin levels, skeletal muscle citrate synthase activity or mRNA expression of the genes measured in muscle. AM251 treatment had no effect on white fat UCP1 expression levels. AM251 decreased fat pad mass, altered plasma hormone levels, but did not induce browning of WAT defined by UCP1 mRNA levels or alter gene expression in muscle treated acutely with adiponectin, demonstrating the complexity of the endocannabinoid system and metabolism. The CB1 ligand AM251 increased systemic inflammation suggesting limitations on its use in metabolic disorders.<\/jats:p>","DOI":"10.3390\/ijms231911447","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T22:53:19Z","timestamp":1664405599000},"page":"11447","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["CB1 Ligand AM251 Induces Weight Loss and Fat Reduction in Addition to Increased Systemic Inflammation in Diet-Induced Obesity"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0264-0007","authenticated-orcid":false,"given":"Lannie","family":"O'Keefe","sequence":"first","affiliation":[{"name":"Institute for Health and Sport, Victoria University, P.O. Box 14428, Melbourne, VIC 8001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Vu","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University, P.O. Box 14428, Melbourne, VIC 8001, Australia"},{"name":"Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna C.","family":"Simcocks","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University, P.O. Box 14428, Melbourne, VIC 8001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayte A.","family":"Jenkin","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University, P.O. Box 14428, Melbourne, VIC 8001, Australia"},{"name":"School of Science, Western Sydney University, Campbelltown, NSW 2560, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Mathai","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University, P.O. Box 14428, Melbourne, VIC 8001, Australia"},{"name":"The Florey Institute of Neuroscience and Mental Health, Parkville, Melbourne, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1697-8890","authenticated-orcid":false,"given":"Deanne H.","family":"Hryciw","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University, P.O. Box 14428, Melbourne, VIC 8001, Australia"},{"name":"School of Environment and Sciences, Griffith University, Nathan, QLD 4111, Australia"},{"name":"Griffith Institute for Drug Discovery, Griffith University, Nathan, QLD 4111, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana S.","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8762-4865","authenticated-orcid":false,"given":"Andrew J.","family":"McAinch","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University, P.O. Box 14428, Melbourne, VIC 8001, Australia"},{"name":"Australian Institute for Musculoskeletal Science (AIMSS), Victoria University, Melbourne, VIC 8001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1056\/NEJMoa044537","article-title":"Effects of Rimonabant on Metabolic Risk Factors in Overweight Patients with Dyslipidemia","volume":"353","author":"Golay","year":"2005","journal-title":"N. Engl. J. 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