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 μM ouabain. CD36 expression was suppressed by 0.2 μM 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)Obvious fatty infiltration was found in noninjected Tg mice but not in the mice injected wit 40 ng of ouabain. In conclusion, low-dose exogenous ouabain increased Na+/K+-ATPase activity, suppressed C-reactive protein mediated CD3 expression, and alleviated murine cardiac lipotoxicity in vitro and in vivo.