Adiponectin inhibits leptin‐induced cardiomyocyte hypertrophy by attenuation of calcineurin/NFAT activation

Abstract

Leptin and adiponectin are adipokines which exert opposite effects on cardiac pathology. Leptin induces cardiomyocyte hypertrophy and hyperleptinemia has been shown to be a risk factor for developing heart failure. In contrast adiponectin is antihypertrophic and reduced plasma adiponectin levels constitute a cardiovascular risk factor. In the present study we determined whether adiponectin can modify leptin‐induced hypertrophy in cultured rat ventricular myocytes. Leptin (3.1 nM) treatment for 24 h produced a robust hypertrophy as evidenced by significantly increased cell surface area, α‐skeletal actin gene expression and rate of protein synthesis. These effects were associated with significantly increased calcineurin activity and import of the transcriptional factor NFAT3 into nuclei. The leptin–induced calcineurin activation was paralleled by increased intracellular Na+ and Ca2+ concentrations. The pro‐hypertrophic effect of leptin was completely prevented in myocytes co‐treated with adiponectin (0.5 μM). These effects were associated with attenuation of leptin‐induced elevations in intracellular Na+ and Ca2+ concentrations, calcineurin activation and NFAT3 nuclear translocation. Thus, adiponectin may represent an endogenous factor mitigating the pro‐hypertrophic effect of leptin by preventing calcineurin activation. Supported by the Canadian Institutes of Health Research.