Ca2+ mishandling and cardiac dysfunction in obesity and insulin resistance: Role of oxidative stress

Obesity and insulin resistance (IR) are strongly connected to the development of subclinical cardiac dysfunction and eventually can lead to heart failure, which is the main cause of morbidity and death in patients having these metabolic diseases. It has been considered that excessive fat tissue may play a critical role in producing systemic IR and enhancing reactive oxygen species (ROS) generation. This oxidative stress (OS) may elicit or exacerbate IR. On the other hand, evidence suggests that some of the cellular mechanisms involved in the pathophysiology of obesity and IR-related cardiomyopathy are excessive myocardial ROS production and abnormal Ca2+ homeostasis. In addition, emerging evidence suggests that augmented ROS production may contribute to Ca2+ mishandling by affecting the redox state of key proteins implicated in this process. In this review, we focus on the role of Ca2+ mishandling in the development of cardiac dysfunction in obesity and IR and address the evidence suggesting that OS might also contribute to cardiac dysfunction by affecting Ca2+ handling. (C) 2014 Elsevier Ltd. All rights reserved.