{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T04:51:11Z","timestamp":1773204671440,"version":"3.50.1"},"reference-count":71,"publisher":"Bioscientifica","issue":"3","license":[{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>Combination therapies with gut hormone analogs represent promising treatment strategies for obesity. This pilot study investigates the therapeutic potential of modulators of the glucagon-like peptide 1 (GLP-1) and neuropeptide Y (NPY) system using GLP-1 receptor agonists (semaglutide) and antagonists (exendin 9-39), as well as non-selective and NPY-Y2-receptor selective peptide tyrosine tyrosine (PYY) analogs (PYY3-36\/NNC0165-0020 and NNC0165-1273) and an NPY-Y2 receptor antagonist (JNJ31020028).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>High-fat diet (HFD)-induced obese rats were randomized into following treatment groups: group 1, nonselective PYY analog\u2009+\u2009semaglutide (<jats:italic>n<\/jats:italic>\u2009=\u20094); group 2, non-selective and NPY-Y2 receptor selective PYY analog\u2009+\u2009semaglutide (<jats:italic>n<\/jats:italic>\u2009=\u20092); group 3, GLP-1 receptor antagonist\u2009+\u2009NPY-Y2 receptor antagonist (<jats:italic>n<\/jats:italic>\u2009=\u20093); group 4, semaglutide (<jats:italic>n<\/jats:italic>\u2009=\u20095); and group 5, control (<jats:italic>n<\/jats:italic>\u2009=\u20095). Animals had free access to HFD and low-fat diet. Food intake, HFD preference and body weight were measured daily.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>A combinatory treatment with a non-selective PYY analog and semaglutide led to a maximum body weight loss of 14.0 \u00b1 4.9% vs 9.9 \u00b1 1.5% with semaglutide alone. Group 2 showed a maximum weight loss of 20.5 \u00b1 2.4%. While HFD preference was decreased in group 2, a strong increase in HFD preference was detected in group 3.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>PYY analogs (especially NPY-Y2 selective receptor agonists) could represent a promising therapeutic approach for obesity in combination with GLP-1 receptor agonists. Additionally, combined GLP-1 and PYY3-36 receptor agonists might have beneficial effects on food preference.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/ec-23-0398","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T17:30:14Z","timestamp":1706808614000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":14,"title":["GLP-1 and PYY for the treatment of obesity: a pilot study on the use of agonists and antagonists in diet-induced rats"],"prefix":"10.1530","volume":"13","author":[{"given":"Marie","family":"Oertel","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}]},{"given":"Christian G","family":"Ziegler","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden, Dresden, Germany"}]},{"given":"Michael","family":"Kohlhaas","sequence":"additional","affiliation":[{"name":"Comprehensive Heart Failure Center, W\u00fcrzburg, Germany"}]},{"given":"Alexander","family":"Nickel","sequence":"additional","affiliation":[{"name":"Comprehensive Heart Failure Center, W\u00fcrzburg, Germany"}]},{"given":"Simon","family":"Kloock","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}]},{"given":"Christoph","family":"Maack","sequence":"additional","affiliation":[{"name":"Comprehensive Heart Failure Center, W\u00fcrzburg, Germany"}]},{"given":"Vasco","family":"Sequeira","sequence":"additional","affiliation":[{"name":"Comprehensive Heart Failure Center, W\u00fcrzburg, Germany"}]},{"given":"Martin","family":"Fassnacht","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4885-9355","authenticated-orcid":true,"given":"Ulrich","family":"Dischinger","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"Comprehensive Heart Failure Center, W\u00fcrzburg, Germany"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Lancet","first-page":"2627","article-title":"Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128\u00b79 million children, adolescents, and adults","volume":"390","year":"2017","unstructured":"NCD Risk Factor Collaboration (NCD-RisC). 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