Influência da oxidação de glicose sobre a função miocárdica de ratos obesos

Abstract

EPÍGRAFE ´1HQKXP YHQWR VRSUD D IDYRU GH TXHP QmR VDEH SDUD RQGH LUµ 6rQHFD RESUMOObesidade é uma doença metabólica crônica definida pelo acúmulo excessivo do tecido adiposo em relação à massa magra tecidual. Estudos clínicos mostram que a obesidade está associada à disfunção ventricular diastólica e não consistente comprometimento do desempenho sistólico. Os modelos experimentais que induzem obesidade por dietas têm sido utilizados como alternativa para se estudar as conseqüências das anormalidades cardíacas decorrentes do acúmulo de gordura.Pesquisas mostram que a função cardíaca em animais obesos pode estar preservada, diminuída ou aumentada. Alterações nos substratos energéticos, inibição da via glicolítica pelos ácidos graxos e redução na atividade da enzima piruvato desidrogenase (PDH) podem contribuir para a disfunção cardíaca induzida pela obesidade. Em razão da ausência de pesquisas que avaliaram a relação entre função cardíaca e metabolismo energético na obesidade, o objetivo deste estudo foi testar a hipótese que o desequilíbrio energético miocárdico, entre ácidos graxos e glicose, ocasionado pela obesidade, acarreta disfunção cardíaca. O prejuízo funcional nos animais obesos é decorrente de déficit de adenosina trifosfato (ATP), via glicolítica, para a bomba de cálcio (Ca 2+ ) do retículo sarcoplasmático (SERCA2). Wistar rats were assigned to one of two groups (n=30 each): control (C) and obese (Ob). The C group was fed a standard diet and Ob group was fed cycles of four highfat diets for 30 weeks. The total body fat was measured from the sum of the individual fat pad weights (epididymal, retroperitoneal and visceral) and the obesity defined by adiposity index. The nutritional and metabolic profiles of these animals were also evaluated. The cardiac remodeling process was assessed by structural and functional analysis. The structure was analyzed post-death for macroscopic study.Myocardial performance of isolated papillary muscle from the left ventricle (LV) was evaluated by under baseline conditions and after inotropic maneuvers. Comparisons between experimental groups (control and obese rats) were performed using Students-t test for independent samples. The cardiac function, after inotropic maneuvers, was analyzed by two-way analysis of variance (ANOVA) for repeated measures and complemented by Student-Newman-Keuls's posthoc test for specific differences. The level of significance considered was 5 %. Obesity promoted glucose intolerance, hyperinsulinemia, hyperleptinemia and insulin resistance after 30 weeks.However, the behavior of systolic blood pressure was similar between groups. The post-death macroscopic study showed that obesity doesn't promote to an increase in heart weight and heart chambers at 30 weeks. Obesity did not cause myocardial stiffness and damage on cardiac function under baseline conditions. Several inotropic maneuvers no make evident changes between control and obese, since the behavior of developed tension (DT) was similar between the groups. The return values of DT and resting ...