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Cardiometabolism

Bile acid receptor protects against diabetic cardiomyopathy

Nature Reviews Cardiology (2024)Cite this article

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Toxic accumulation of lipids in the heart is a major contributor to the cardiac remodelling and dysfunction that occurs in individuals with diabetic cardiomyopathy. A study now shows that activation of the G-protein-coupled bile acid receptor 1 (GPBAR1; also known as TGR5) inhibits CD36-mediated fatty acid uptake in cardiomyocytes and protects against cardiac lipotoxicity and the development of diabetic cardiomyopathy in mice. “Cardiac lipotoxicity has long been an unresolved issue in diabetic cardiomyopathy. Therefore, deciphering the regulatory mechanisms of cardiac lipid metabolism will have a profound effect on the treatment of this condition,” say study investigators Hu Wang, Changtao Jiang and Ming Xu.

Cardiomyocyte-specific deletion of Tgr5 aggravated cardiac hypertrophy, fibrosis and dysfunction in both mouse models. Cardiac TGR5 deficiency exacerbated myocardial dysfunction by increasing fatty acid uptake by cardiomyocytes and promoting lipid accumulation in the heart. By contrast, administration of the TGR5-specific agonist INT-777 or the bile acids deoxycholic acid (DCA) and taurocholic acid (TCA) improved cardiac function and reduced cardiac lipid accumulation and remodelling in the diabetic mouse models.

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  • Ritterhoff, J. & Tian, R. et al. Metabolic mechanisms in physiological and pathological cardiac hypertrophy: new paradigms and challenges. Nat. Rev. Cardiol. 20, 812–829 (2023)

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  1. Nature Reviews Cardiology http://www.nature.com/nrcardio/

    Irene Fernández-Ruiz

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  1. Irene Fernández-Ruiz
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Correspondence to Irene Fernández-Ruiz.

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Fernández-Ruiz, I. Bile acid receptor protects against diabetic cardiomyopathy. Nat Rev Cardiol (2024). https://doi.org/10.1038/s41569-024-01040-y

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  • DOI: https://doi.org/10.1038/s41569-024-01040-y

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