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Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):E771-E780. doi: 10.1073/pnas.1610968114. Epub 2017 Jan 17.

Atrial natriuretic peptide regulates adipose tissue accumulation in adult atria.

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Faculté de Médecine, Université Pierre et Marie Curie, Sorbonne University, INSERM UMR_S1166, Paris, France.
Faculté de Médecine La Timone, Université Aix-Marseille, INSERM UMR_910, Marseille, France.
Department of Cardiology, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
INSERM UMR_S999, Laboratory of Excellence in Research on Medication and Innovative Therapeutics, Institut Paris-Sud d'Innovation Thérapeutique Centre Chirurgical Marie Lanelongue, 92350 Le Plessis-Robinson, France.
Institute of Cardiometabolism and Nutrition, Paris, France.
INSERM U_955, Département Hospitalo-Universitaire Ageing-Thorax-Vessels-Blood, Département de Physiologie, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Creteil, France.
Faculté de Médecine, Université Pierre et Marie Curie, Sorbonne University, INSERM UMR_S1166, Paris, France;


The abundance of epicardial adipose tissue (EAT) is associated with atrial fibrillation (AF), the most frequent cardiac arrhythmia. However, both the origin and the factors involved in EAT expansion are unknown. Here, we found that adult human atrial epicardial cells were highly adipogenic through an epithelial-mesenchymal transition both in vitro and in vivo. In a genetic lineage tracing the WT1CreERT2+/-RosatdT+/- mouse model subjected to a high-fat diet, adipocytes of atrial EAT derived from a subset of epicardial progenitors. Atrial myocardium secretome induces the adipogenic differentiation of adult mesenchymal epicardium-derived cells by modulating the balance between mesenchymal Wingless-type Mouse Mammary Tumor Virus integration site family, member 10B (Wnt10b)/β-catenin and adipogenic ERK/MAPK signaling pathways. The adipogenic property of the atrial secretome was enhanced in AF patients. The atrial natriuretic peptide secreted by atrial myocytes is a major adipogenic factor operating at a low concentration by binding to its natriuretic peptide receptor A (NPRA) receptor and, in turn, by activating a cGMP-dependent pathway. Hence, our data indicate cross-talk between EAT expansion and mechanical function of the atrial myocardium.


atrial natriuretic peptide; cGMP; epicardial adipose tissue; epicardial progenitors

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