title: Apelin administration ameliorates high fat diet-induced cardiac hypertrophy and contractile dysfunction.
abstract: Apelin has been recognized as an adipokine that plays an important role in regulating energy metabolism and is credited with antiobesity and antidiabetic properties. This study was designed to examine the effect of exogenous apelin on obesity-associated cardiac dysfunction. Oral glucose tolerance test, echocardiography, cardiomyocyte contractile and intracellular Ca(2+) properties were assessed in adult C57BL/6J mice fed - low or a - high-fat diet for 24weeks followed by apelin treatment (100nmol/kg, i.p. for 2weeks). High-fat diet resulted in increased left ventricular diastolic and systolic diameters, and wall thickness, compromised fractional shortening, impaired cardiomyocyte mechanics (peak-shortening, maximal velocity of shortening/relengthening, and duration of shortening and relengthening) and compromised intracellular Ca(2+) handling, all of which were reconciled by apelin. Apelin treatment also reversed high fat diet-induced changes in intracellular Ca(2+) regulatory proteins, ER stress, and autophagy. In addition, microRNAs (miR) -133a, miR-208 and miR-1 which were elevated following high-fat feeding were attenuated by apelin treatment. In cultured cardiomyocytes apelin reconciled palmitic acid-induced cardiomyocyte contractile anomalies. Collectively, these data depict a pivotal role of apelin in obesity-associated cardiac contractile dysfunction, suggesting a therapeutic potential of apelin in the management of cardiac dysfunction associated with obesity.
authors.affiliation: Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY, USA.
authors.forename: Asli F
authors.initials: AF
authors.lastname: Ceylan-Isik
authors.forename: Machender R
authors.initials: MR
authors.lastname: Kandadi
authors.forename: Xihui
authors.initials: X
authors.lastname: Xu
authors.forename: Yinan
authors.initials: Y
authors.lastname: Hua
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Chicco
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.forename: Sreejayan
authors.initials: S
authors.lastname: Nair
mesh_terms: D054392:Adipokines; D000818:Animals; D000073861:Apelin; D001343:Autophagy / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D020738:Leptin / Q000097:blood; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
chemical_list: D054392:Adipokines; D000073861:Apelin; C402826:Apln protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D035683:MicroRNAs; D014280:Triglycerides; D019308:Palmitic Acid; D005947:Glucose
keywords: Apelin; High fat-diet; Hypertrophy; Obesity