Low-dose Exogenous Ouabain Alleviates Cardiac Lipotoxicity Through Suppressing Expression of CD36.

CD36 is a key transporter involved in fatty acid (FA) uptake and contributes to the accumulation of FA in cardiomyocytes. The objective of this study was to investigate the role of ouabain, a glycoside regulator of Na+/K+-ATPase, in the regulation of CD36 expression and FA accumulation. FATP1 transgenic (Tg) mice with lipotoxic cardiomyopathy displayed significantly increased cardiac CD36 expression and free fatty acid accumulation. The data on enzyme-linked immunosorbent assay showed that endogenous ouabain was decreased in the serum of Tg mice versus wild-type mice. CD36 expression and free fatty acid accumulation in their primary cardiomyocytes were abated by treatment with 0.15-0.30 M ouabain. CD36 expression was suppressed by 0.2 M ouabain treatment, and the suppression was rescued by C-reactive protein. CD36 expression and free fatty acid accumulation in the heart were markedly reduced in Tg mice injected with 30 or 40 ng of ouabain (P < 0.01). Obvious fatty infiltration was found in noninjected Tg mice but not in the mice injected with 40 ng of ouabain. In conclusion, low-dose exogenous ouabain increased Na+/K+-ATPase activity, suppressed C-reactive protein-mediated CD36 expression, and alleviated murine cardiac lipotoxicity in vitro and in vivo.