title: Comparisons of cardioprotective efficacy between fibroblast growth factor 21 and dipeptidyl peptidase-4 inhibitor in prediabetic rats.
abstract: OBJECTIVE
  Comparative efficacy between fibroblast growth factor 21 (FGF21) and vildagliptin on metabolic regulation, cardiac mitochondrial function, heart rate variability (HRV), and left ventricular (LV) function is not known. We hypothesized that FGF21 and vildagliptin share a similar efficacy in improving these parameters in high fat diet (HFD)-induced obese-insulin resistant rats.
  
  
  METHODS
  Twenty-four male Wistar rats were fed with either a normal diet (ND) or a HFD for 12 weeks. 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 mg/kg/d, ip; HFF), or vildagliptin (3 mg/kg/d, PO; HFVil) for 28 days.
  
  
  RESULTS
  HFV rats developed obese-insulin resistance, increased serum tumor necrosis factors alpha (TNF-α) 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-cell lymphoma 2 (Bcl-2) with increased Bcl2-associated X-protein (Bax) and cleaved caspase 3 expression. Cardiac FGF21 signaling pathways were markedly decreased in HFV rats indicated by decreased phosphor-fibroblast growth factor receptors 1 (p-FGFR1), phosphor-extracellular signal-regulated protein kinases 1 (p-ERK1/2), proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and carnitine palmitoyltransferase-1 (CPT-1) expression. Although both FGF21 and vildagliptin similarly attenuated these impairments, only HFF rats had decreased body weight, visceral fat, and serum TNF-α levels.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Pongpan
authors.initials: P
authors.lastname: Tanajak
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Piangkwan
authors.initials: P
authors.lastname: Sa-Nguanmoo
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Nattayaporn
authors.initials: N
authors.lastname: Apaijai
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand.|Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Siriporn C
authors.initials: SC
authors.lastname: Chattipakorn
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Nipon
authors.identifier: http://orcid.org/0000-0003-3026-718X
authors.initials: N
authors.lastname: Chattipakorn
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D058065:Diabetic Cardiomyopathies / Q000000981:diagnostic imaging / Q000517:prevention & control*; D059305:Diet, High-Fat; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005346:Fibroblast Growth Factors / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects; D009570:Nitriles / Q000627:therapeutic use; D009765:Obesity / Q000150:complications / Q000503:physiopathology; D011236:Prediabetic State / Q000150:complications* / Q000188:drug therapy*; D011759:Pyrrolidines / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000517:prevention & control; D000077597:Vildagliptin
chemical_list: D002316:Cardiotonic Agents; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D009570:Nitriles; D011759:Pyrrolidines; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D000077597:Vildagliptin; D000218:Adamantane
keywords: Cardiac function; Cardiac mitochondrial function; Dipeptidyl peptidase-4 inhibitor; Fibroblast growth factor 21; Metabolic regulation