Rep resentative M mode echocardiography tracings are shown in Figure 6 and summarized in Additional file 2 Table S2. Discussion The adipocytokine selleck inhibitor leptin may link obesity with cardiac hypertrophy, an important risk factor for the develop ment of heart failure. Studies in humans and ro dents have shown that obesity is associated with LV hypertrophy, and body mass index was identified as a strong and independent predictor of LV mass. Im portantly, cardiac hypertrophy is also observed in normotensive obese subjects, and plasma leptin levels are associated with increased myocardial wall thickness independent of BW or blood pressure elevations, suggesting a causal role for leptin in the pathogenesis of cardiac hypertrophy.

Although the major source of leptin is adipose tissue, cardiomyocytes are also capable of synthesizing leptin, and increased cardiac leptin levels have been Inhibitors,Modulators,Libraries reported in mice or rats following Inhibitors,Modulators,Libraries coronary ligation or in patients with heart failure. In this study, elevated circulating as well as cardiac leptin levels were detected in both diet induced and genetically obese mice, which may have acted on cardiomyocytes as well as other, non cardiomyocyte cells expressing leptin re ceptors. Although leptin serum levels were higher than in previous publications, we explain this find ings with the higher age of the mice, a factor previously found to be associated with increased circulating leptin levels. Leptin has been shown to stimulate the hyper trophy of cardiomyocytes isolated from rats or humans.

Moreover, chronic leptin infusion in creased cardiac ANP expression after Inhibitors,Modulators,Libraries myocardial infarc tion in mice, whereas neutralizing LepR antibodies abrogated the hypertrophy of the surviving myocardium after coronary artery ligation in rats. On the other hand and as confirmed in our analysis, cardiac hypertrophy also develops in leptin and LepR deficient mice and may be reversed by leptin substitution. Cal oric restriction experiments suggested that the anti hypertrophic effects of leptin had occurred in addition to weight loss, which itself may preserve heart function and attenuate LV remodeling. Thus, it is unclear whether the cardiac hypertrophy in obesity is the conse quence of pro hypertrophic effects of the adipokine or ra ther the result of a resistance towards leptins preventive effects on hypertrophic cardiac remodeling.

Of note, since body weight is markedly elevated in the diet induced and particularly, the genetically obese mice, Inhibitors,Modulators,Libraries the heart to body weight ratio decreases, even though the absolute heart Inhibitors,Modulators,Libraries weight is increased. Obesity is associated with elevated circulating lep tin levels and hypothalamic resistance to the weight reducing effects of the adipokine, whereas the existence of a peripheral Binimetinib leptin resistance is contro versial.