title: Bile acid excess induces cardiomyopathy and metabolic dysfunctions in the heart.
abstract: 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.
  
  
  
  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).
authors: Section of Pediatric Critical Care, Baylor College of Medicine, Houston, TX.
authors: Moreshwar S
authors: MS
authors: Desai
authors: Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL.
authors: Bhoomika
authors: B
authors: Mathur
authors: Section of Pediatric Critical Care, Baylor College of Medicine, Houston, TX.
authors: Zeena
authors: Z
authors: Eblimit
authors: Department of Cardiology, University of Texas Health Sciences Center, Houston, TX.
authors: Hernan
authors: H
authors: Vasquez
authors: Department of Cardiology, University of Texas Health Sciences Center, Houston, TX.
authors: Heinrich
authors: H
authors: Taegtmeyer
authors: Pediatric Gastroenterology, Emory School of Medicine, Atlanta, GA.
authors: Saul J
authors: SJ
authors: Karpen
authors: Department of Pediatric Cardiology, Baylor College of Medicine, Houston, TX.
authors: Daniel J
authors: DJ
authors: Penny
authors: Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.
authors: David D
authors: DD
authors: Moore
authors: Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL.
authors: Sayeepriyadarshini
authors: S
authors: Anakk
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000097:blood / Q000502:physiology*; D009202:Cardiomyopathies / Q000097:blood / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D005227:Fatty Acids / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout
chemical_list: D001647:Bile Acids and Salts; D005227:Fatty Acids