title: Long-term obesity promotes alterations in diastolic function induced by reduction of phospholamban phosphorylation at serine-16 without affecting calcium handling.
abstract: Few studies have evaluated the relationship between the duration of obesity, cardiac function, and the proteins involved in myocardial calcium (Ca(2+)) handling. We hypothesized that long-term obesity promotes cardiac dysfunction due to a reduction of expression and/or phosphorylation of myocardial Ca(2+)-handling proteins. Thirty-day-old male Wistar rats were distributed into two groups (n = 10 each): control (C; standard diet) and obese (Ob; high-fat diet) for 30 wk. Morphological and histological analyses were assessed. Left ventricular cardiac function was assessed in vivo by echocardiographic evaluation and in vitro by papillary muscle. Cardiac protein expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a), calsequestrin, L-type Ca(2+) channel, and phospholamban (PLB), as well as PLB serine-16 phosphorylation (pPLB Ser(16)) and PLB threonine-17 phosphorylation (pPLB Thr(17)) were determined by Western blot. The adiposity index was higher (82%) in Ob rats than in C rats. Obesity promoted cardiac hypertrophy without alterations in interstitial collagen levels. Ob rats had increased endocardial and midwall fractional shortening, posterior wall shortening velocity, and A-wave compared with C rats. Cardiac index, early-to-late diastolic mitral inflow ratio, and isovolumetric relaxation time were lower in Ob than in C. The Ob muscles developed similar baseline data and myocardial responsiveness to increased extracellular Ca(2+). Obesity caused a reduction in cardiac pPLB Ser(16) and the pPLB Ser(16)/PLB ratio in Ob rats. Long-term obesity promotes alterations in diastolic function, most likely due to the reduction of pPLB Ser(16), but does not impair the myocardial Ca(2+) entry and recapture to SR.
authors: Center for Physical Education and Sports, Department of Sports, Federal University of Espírito Santo, Vitória; anapaula@cefd.ufes.br.
authors: Ana Paula
authors: AP
authors: Lima-Leopoldo
authors: Center for Physical Education and Sports, Department of Sports, Federal University of Espírito Santo, Vitória;
authors: André S
authors: AS
authors: Leopoldo
authors: Department of Clinic and Cardiology, School of Medicine, Universidade Estadual Paulista, Botucatu, São Paulo; and.
authors: Danielle C T
authors: DC
authors: da Silva
authors: Department of Clinic and Cardiology, School of Medicine, Universidade Estadual Paulista, Botucatu, São Paulo; and.
authors: André F
authors: AF
authors: do Nascimento
authors: Department of Clinic and Cardiology, School of Medicine, Universidade Estadual Paulista, Botucatu, São Paulo; and.
authors: Dijon H S
authors: DH
authors: de Campos
authors: Department of Clinic and Cardiology, School of Medicine, Universidade Estadual Paulista, Botucatu, São Paulo; and.
authors: Renata A M
authors: RA
authors: Luvizotto
authors: Department of Clinic and Cardiology, School of Medicine, Universidade Estadual Paulista, Botucatu, São Paulo; and.
authors: Adriana F
authors: AF
authors: de Deus
authors: Department of Clinic and Cardiology, School of Medicine, Universidade Estadual Paulista, Botucatu, São Paulo; and.
authors: Paula P
authors: PP
authors: Freire
authors: Department of Biosciences, Federal University of São Paulo, Santos, Brazil.
authors: Alessandra
authors: A
authors: Medeiros
authors: Department of Clinic and Cardiology, School of Medicine, Universidade Estadual Paulista, Botucatu, São Paulo; and.
authors: Katashi
authors: K
authors: Okoshi
authors: Department of Clinic and Cardiology, School of Medicine, Universidade Estadual Paulista, Botucatu, São Paulo; and.
authors: Antonio C
authors: AC
authors: Cicogna
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D003971:Diastole; D006321:Heart / Q000503:physiopathology*; D006331:Heart Diseases / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000473:pathology; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D010210:Papillary Muscles / Q000473:pathology / Q000503:physiopathology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D014463:Ultrasonography; D000099211:Phospholamban
chemical_list: D002118:Calcium; D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D012694:Serine; D000099211:Phospholamban
keywords: Ca2+-handling proteins; PLB serine-16 phosphorylation; cardiac dysfunction; high-fat diet; obesity