Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetics in obesity

Article

关键词: ACTIVATED RECEPTOR-ALPHA;    DIABETIC DB/DB MICE;    SKELETAL-MUSCLE;    ENERGY-METABOLISM;    RAT-HEART;    CARDIAC-FUNCTION;    PROTEIN-3;    TISSUE;    CONTRACTILITY;    DYSFUNCTION;   

DOI  :  10.1161/CIRCULATIONAHA.105.554360

来源: SCIE

【 摘 要 】

Background-Obesity is a risk factor for cardiovascular disease and is strongly associated with insulin resistance and type 2 diabetes. Recent studies in obese humans and animals demonstrated increased myocardial oxygen consumption (MVO2) and reduced cardiac efficiency (CE); however, the underlying mechanisms remain unclear. The present study was performed to determine whether mitochondrial dysfunction and uncoupling are responsible for reduced cardiac performance and efficiency in ob/ob mice. Methods and Results-Cardiac function, MVo(2), mitochondrial respiration, and ATP synthesis were measured in 9-week-old ob/ob and control mouse hearts. Contractile function and MVO2 in glucose-perfusedob/ ob hearts were similar to controls under basal conditions but were reduced under high workload. Perfusion of ob/ob hearts with glucose and palmitate increased MVO2 and reduced CE by 23% under basal conditions, and CE remained impaired at high workload. In glucose-perfused ob/ob hearts, mitochondrial state 3 respirations were reduced but ATP/O ratios were unchanged. In contrast, state 3 respiration rates were similar in ob/ob and control mitochondria from hearts perfused with palmitate and glucose, but ATP synthesis rates and ATP/O ratios were significantly reduced in ob/ob, which suggests increased mitochondrial uncoupling. Pyruvate dehydrogenase activity and protein levels of complexes I, III, and V were reduced in obese mice. Conclusions-These data indicate that reduced mitochondrial oxidative capacity may contribute to cardiac dysfunction in ob/ob mice. Moreover, fatty acid but not glucose-induced mitochondrial uncoupling reduces CE in obese mice by limiting ATP production and increasing MVO2.

【 授权许可】

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