Exosomal microRNA-194 causes cardiac injury and mitochondrial dysfunction in obese mice

Highlights: • Circulating miR-194 level positively correlated with human cardiac dysfunction. • Exosomal miR-194 impairs mitochondrial activity. • MiR-194 inhibitor protects diet-induced mouse cardiomyopathy. Obesity is associated with increased cardiovascular morbidity and mortality, but the effects of circulating factors on cardiac function is not fully elucidated. Present study aims to explore the pathophysiological role of microRNA (miR)-194, one of hepatic enriched miRs, in the process of obesity-related cardiomyopathy in human subjects and mice. The expression level of circulating exosomal miR-194 was measured in 39 lean and 35 obese human subjects, and correlated with cardiac parameters. The effects of miR-194 on mitochondrial activity and cardiac function were investigated by administration of miR-194 sponge in mouse cardiomyocytes and obesity-related cardiomyopathy. The upregulation of circulating miR-194 level was closely correlated with impaired human cardiac function, including ejection fraction (r = −0.5002, p In vivo mouse study, high fat diet damaged cardiac function, normal structure and mitochondrial activity, whereas miR-194 sponge improved the cardiac status. Present study uncovered the correlation between circulating miR-194 and cardiac parameters in human subjects, and provided solid evidence of the therapeutic application of miR-194 sponge in combating obesity-mediated cardiac dysfunction.