Atrial natriuretic peptide regulates adipose tissue accumulation in adult atria

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 114; no. 5; pp. E771 - E780
• Main Authors: Suffee, Nadine, Moore-Morris, Thomas, Farahmand, Patrick, Rücker-Martin, Catherine, Dilanian, Gilles, Fradet, Magali, Sawaki, Daigo, Derumeaux, Geneviève, LePrince, Pascal, Clément, Karine, Dugail, Isabelle, Puceat, Michel, Hatem, Stéphane N.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 31.01.2017
• Series: PNAS Plus
• Subjects: Adipocytes; Biological Sciences; Cardiac arrhythmia; Genetics; Human genetics; Life Sciences; Peptides; PNAS Plus; Tissues; Tumors; cGMP; epicardial adipose tissue; epicardial progenitors; atrial natriuretic peptide
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1610968114

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.