Obesity-related cardiomyopathy is an adipocyte-mediated paracrine disease.

Obesity is associated with an increased burden of chronic diseases, including diabetes mellitus, hypertension, and coronary atherosclerosis, all of which contribute to higher rates of morbidity and mortality in obese patients. This was confirmed in a prospective study that demonstrated a 2–3-fold increase in mortality in obese as compared to normal weight individuals [1]. The World Health Organization currently estimates that by 2015, approximately 700 million adults worldwide will be obese (body mass index 430 kg/m 2 ) with another 2.3 billion adults being categorized as overweight (body mass index 25–29 kg/m 2 ) [2]. Based on this prediction, it is expected that there will be an attendant increase in obesity-related cardiovascular disorders. It is increasingly recognized that cardiac remodeling and dysfunction that occurs as a consequence of obesity cannot be attributed solely to the comorbidities associated with excess weight. In fact, the Coronary Artery Risk Development in Young Adults (CARDIA) study found that over a 25-year follow-up period obesity was highly related to left ventricular dysfunction even after adjusting for baseline and interval changes in other risk factors [3] .I n this issue ofTrends in Cardiovascular Medicine, Mahajan et al. [4] review cardiac dysfunction in obesity with a focus on cardiac metabolism and fibrosis. They present an overview of left ventricular remodeling, systolic dysfunction, and diastolic dysfunction; discuss changes in metabolism as a contributor to decreased myocardial performance; and review mediators of fibrosis that are upregulated in obesity and participate in cardiac remodeling. There are several interesting points raised by this review. The first is that there is no consensus opinion on what defines the obesity-related cardiomyopathy. Evidence presented suggests that this cardiomyopathy includes left heart remodeling (i.e., left atrial dilation and left ventricular hypertrophy) as well as abnormalities in left ventricular contractile and relaxation functions. The second is that the obesity-related cardiomyopathy may be a paracrine disorder owing to factors secreted by dysfunctional adipocytes in close apposition to atrial and ventricular cardiomyocytes. Third, despite differences in etiology, obesity-related cardiomyopathy appears to have the same aberrant shifts in metabolism as other cardiomyopathies. Finally, like other chronic diseases, obesity facilitates cardiac fibrosis, which may predispose to cardiac dysfunction and adverse cardiovascular outcomes. The confusion as to what features comprise the cardiomyopathy of obesity may have occurred, in part, from conflicting data reported by prior studies. One potential explanation for these discordant results is that obesity is not a uniform disorder and individuals enrolled in clinical studies may represent a heterogeneous group. For example, obesity is typically determined by body mass index, a metric that does not take into account body fat distribution. Although excess visceral adipose tissue is associated with adverse cardiac events, subcutaneous obesity with minimal visceral fat has a lower cardiac risk profile [5]. This suggests that studies that enroll patients based on body mass index plus other measures of adipose tissue distribution, such as waist circumference and waist-to-hip ratios, will likely lead to more reproducible findings and aid in defining obesity-related cardiomyopathy [6]. The concept that obesity-related cardiomyopathy is manifested as left ventricular hypertrophy with predominantly diastolic dysfunction and that this occurs as a result of an adipocyte paracrine effect is not surprising. This is based on observations made in congenital or acquired generalized lipodystrophy, which is characterized by increased extraand intra-cardiac ectopic adipose deposition [7]. In patients with this lipotoxic cardiomyopathy, cardiac magnetic