{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T19:50:25Z","timestamp":1762458625909,"version":"3.34.0"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,9,6]],"date-time":"2012-09-06T00:00:00Z","timestamp":1346889600000},"content-version":"vor","delay-in-days":1528,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity"],"published-print":{"date-parts":[[2008,7]]},"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold>To further address the function of the Y5 receptor in energy homeostasis, we investigated the effects of a novel spironolactone Y5 antagonist in diet\u2010induced obese (DIO) mice.<\/jats:p><jats:p><jats:bold>Methods and Procedures:<\/jats:bold>Male C57BL\/6 or<jats:italic>Npy5r<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice were adapted to high\u2010fat (HF) diet for 6\u201310 months and were submitted to three experimental treatments. First, the Y5 antagonist at a dose of 10 or 30 mg\/kg was administered for 1 month to DIO C57BL\/6 or<jats:italic>Npy5r<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice. Second, the Y5 antagonist at 30 mg\/kg was administered for 1.5 months to DIO C57BL\/6 mice, and insulin sensitivity was evaluated using an insulin tolerance test. After a recovery period, nuclear magnetic resonance measurement was performed to evaluate body composition. Third, DIO mice were treated with the Y5 antagonist alone, or in combination with 10% food restriction, or with another anorectic agent, sibutramine at 10 mg\/kg, for 1.5 months. Plasma glucose, insulin, and leptin levels, and adipose tissue weights were quantified.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold>The spironolactone Y5 antagonist significantly reduced body weight in C57BL DIO mice, but not in<jats:italic>Npy5r<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>DIO mice. The Y5 antagonist produced a fat\u2010selective loss of body weight, and ameliorated obesity\u2010associated insulin resistance in DIO mice. In addition, the Y5 antagonist combined with either food restriction or sibutramine tended to produce greater body weight loss, as compared with single treatment.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold>These findings demonstrate that the Y5 receptor is an important mediator of energy homeostasis in rodents.<\/jats:p>","DOI":"10.1038\/oby.2008.223","type":"journal-article","created":{"date-parts":[[2008,4,17]],"date-time":"2008-04-17T17:23:20Z","timestamp":1208453000000},"page":"1510-1515","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Effects of a Novel Y5 Antagonist in Obese Mice: Combination With Food Restriction or 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