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We hypothesized that FGF21 and vildagliptin share a similar efficacy in improving these parameters in high fat diet (HFD)\u2010induced obese\u2010insulin resistant rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty\u2010four male Wistar rats were fed with either a normal diet (ND) or a HFD for 12\u00a0weeks. Then, ND rats were received vehicle (NDV). Rats in the HFD group were divided into three subgroups to receive either vehicle (HFV), recombinant human FGF21 (rhFGF21, 0.1\u00a0mg\/kg\/d, ip; HFF), or vildagliptin (3\u00a0mg\/kg\/d, PO; HFVil) for 28\u00a0days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HFV rats developed obese\u2010insulin resistance, increased serum tumor necrosis factors alpha (TNF\u2010\u03b1) level, impaired heart rate variability (HRV) together with cardiac mitochondrial dysfunction, and LV dysfunction. Cardiac apoptosis was markedly increased in HFV rats indicated by decreased B\u2010cell lymphoma 2 (Bcl\u20102) with increased Bcl2\u2010associated X\u2010protein (Bax) and cleaved caspase 3 expression. Cardiac FGF21 signaling pathways were markedly decreased in HFV rats indicated by decreased phosphor\u2010fibroblast growth factor receptors 1 (p\u2010FGFR1), phosphor\u2010extracellular signal\u2010regulated protein kinases 1 (p\u2010ERK1\/2), proliferator\u2010activated receptor gamma coactivator 1\u2010alpha (PGC\u20101\u03b1), and carnitine palmitoyltransferase\u20101 (CPT\u20101) expression. Although both FGF21 and vildagliptin similarly attenuated these impairments, only HFF rats had decreased body weight, visceral fat, and serum TNF\u2010\u03b1 levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>FGF21 exerts better metabolic regulation and inflammation reduction than vildagliptin. However, FGF21 and vildagliptin shared a similar efficacy for cardioprotection by improving HRV and LV function.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1755-5922.12263","type":"journal-article","created":{"date-parts":[[2017,4,9]],"date-time":"2017-04-09T12:26:39Z","timestamp":1491740799000},"source":"Crossref","is-referenced-by-count":10,"title":["Comparisons of cardioprotective efficacy between fibroblast growth factor 21 and dipeptidyl peptidase\u20104 inhibitor in prediabetic rats"],"prefix":"10.1111","volume":"35","author":[{"given":"Pongpan","family":"Tanajak","sequence":"first","affiliation":[{"name":"Cardiac Electrophysiology Research and Training Center Faculty of Medicine Chiang Mai University  Chiang Mai Thailand"},{"name":"Cardiac Electrophysiology Unit Department of Physiology Faculty of Medicine Chiang Mai University  Chiang Mai Thailand"},{"name":"Center of Excellence in Cardiac Electrophysiology Research Chiang Mai University  Chiang Mai 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