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However, the effects of geniposide on obesity\u2010related cardiac injury remain unknown. Here, we examine whether geniposide attenuates obesity\u2010related cardiac dysfunction. Adult mice were fed a high\u2010fat diet (HFD) for 24 weeks to induce obesity, with the last 3 weeks including a 21\u2010day treatment with geniposide. Morphological changes, cardiac function, and remodeling were assessed. HFD\u2010induced metabolic syndrome, featured as obesity, hyperglycemia, and cardiac hypertrophy, was prevented by geniposide treatment. Geniposide preserved cardiac function in the obese mice. Furthermore, geniposide attenuated myocardial inflammation and myocyte apoptosis induced by HFD. Geniposide activated AMPK<jats:italic>\u03b1<\/jats:italic> and sirtuin (Sirt1) in vivo and in vitro. <jats:italic>Ampk\u03b1<\/jats:italic> deficiency reversed the inhibitory effects of geniposide on cell loss. <jats:italic>Sirt1<\/jats:italic> deficiency abolished the inhibitory effects of geniposide on inflammation in the cardiomyocytes. Geniposide completely lost its protective effects on <jats:italic>Ampk\u03b1<\/jats:italic> knockout mice after <jats:italic>Sirt1<\/jats:italic> deficiency achieved by a nanoparticle transfection reagent. The activation of Sirt1 by geniposide was abolished by <jats:italic>Glp-1r<\/jats:italic> deficiency in vitro. Geniposide reverses molecular pathology and cardiac dysfunction via both AMPK<jats:italic>\u03b1<\/jats:italic>\u2010 and Sirt1\u2010dependent mechanisms. Geniposide is a potential therapeutic drug for cardiovascular complications induced by obesity.<\/jats:p>","DOI":"10.1155\/2018\/6053727","type":"journal-article","created":{"date-parts":[[2018,11,4]],"date-time":"2018-11-04T23:31:20Z","timestamp":1541374280000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Geniposide Protects against Obesity\u2010Related Cardiac Injury through AMPK<i>\u03b1<\/i>\u2010 and Sirt1\u2010Dependent 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