Excess bile acids induced cardiac hypertrophy, bradycardia, and exercise intolerance in mice, which was reversed by intestinal bile acid sequestration with cholestyramine.
Does intestinal bile acid sequestration with cholestyramine reverse heart dysfunction in a mouse model of bile acid overload?
Bile acid excess induces cardiomyopathy and metabolic dysfunction via decreased PGC-1α expression, which can be reversed by bile acid sequestration.
Cardiac dysfunction in patients with liver cirrhosis is strongly associated with increased serum bile acid concentrations. Here we show that excess bile acids decrease fatty acid oxidation in cardiomyocytes and can cause heart dysfunction, a cardiac syndrome that we term cholecardia. Farnesoid X receptor; Small Heterodimer Partner double knockout mice, a model for bile acid overload, display cardiac hypertrophy, bradycardia, and exercise intolerance. In addition, double knockout mice exhibit an impaired cardiac response to catecholamine challenge. Consistent with this decreased cardiac function, we show that elevated serum bile acids reduce cardiac fatty acid oxidation both in vivo and ex vivo. We find that increased bile acid levels suppress expression of proliferator-activated receptor-γ coactivator 1α, a key regulator of fatty acid metabolism, and that proliferator-activated receptor-γ coactivator 1α overexpression in cardiac cells was able to rescue the bile acid-mediated reduction in fatty acid oxidation genes. Importantly, intestinal bile acid sequestration with cholestyramine was sufficient to reverse the observed heart dysfunction in the double knockout mice. CONCLUSIONS: Decreased proliferator-activated receptor-γ coactivator 1α expression contributes to the metabolic dysfunction in cholecardia so that reducing serum bile acid concentrations may be beneficial against the metabolic and pathological changes in the heart. (Hepatology 2017;65:189-201).
Desai et al. (Mon,) conducted a other in Cholecardia (bile acid-induced cardiomyopathy). Bile acid excess was evaluated on Cardiac function and fatty acid oxidation. Excess bile acids induced cardiac hypertrophy, bradycardia, and exercise intolerance in mice, which was reversed by intestinal bile acid sequestration with cholestyramine.