Lima-Leopoldo Ana Paula, Leopoldo André S, da Silva Danielle C T, do Nascimento André F, de Campos Dijon H S, Luvizotto Renata A M, de Deus Adriana F, Freire Paula P, Medeiros Alessandra, Okoshi Katashi, Cicogna Antonio C
Center for Physical Education and Sports, Department of Sports, Federal University of Espírito Santo, Vitória;
Department of Clinic and Cardiology, School of Medicine, Universidade Estadual Paulista, Botucatu, São Paulo; and.
J Appl Physiol (1985). 2014 Sep 15;117(6):669-78. doi: 10.1152/japplphysiol.00088.2014. Epub 2014 Jun 26.
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.
很少有研究评估肥胖持续时间、心脏功能以及参与心肌钙（Ca(2+)）处理的蛋白质之间的关系。我们假设长期肥胖会由于心肌Ca(2+)处理蛋白的表达和/或磷酸化减少而导致心脏功能障碍。将30日龄雄性Wistar大鼠分为两组（每组n = 10）：对照组（C；标准饮食）和肥胖组（Ob；高脂饮食），持续30周。进行了形态学和组织学分析。通过超声心动图评估在体内和通过乳头肌在体外评估左心室心脏功能。通过蛋白质印迹法测定肌浆网（SR）Ca(2+)-ATP酶（SERCA2a）、肌钙蛋白、L型Ca(2+)通道和受磷蛋白（PLB）的心脏蛋白表达，以及PLB丝氨酸-16磷酸化（pPLB Ser(16)）和PLB苏氨酸-17磷酸化（pPLB Thr(17)）。Ob大鼠的肥胖指数比C大鼠高（82%）。肥胖促进了心脏肥大，但间质胶原水平没有改变。与C大鼠相比，Ob大鼠的心内膜和中层缩短分数、后壁缩短速度和A波增加。Ob组的心脏指数、舒张早期至晚期二尖瓣流入比值和等容舒张时间低于C组。Ob组肌肉的基线数据和心肌对细胞外Ca(2+)增加的反应性相似。肥胖导致Ob大鼠心脏pPLB Ser(16)和pPLB Ser(16)/PLB比值降低。长期肥胖促进舒张功能改变，最可能是由于pPLB Ser(16)减少，但不损害心肌Ca(2+)进入和再摄取到SR。
