title: Atrial natriuretic peptide regulates adipose tissue accumulation in adult atria.
abstract: 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.
authors.affiliation: Faculté de Médecine, Université Pierre et Marie Curie, Sorbonne University, INSERM UMR_S1166, Paris, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Suffee
authors.affiliation: Faculté de Médecine La Timone, Université Aix-Marseille, INSERM UMR_910, Marseille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Moore-Morris
authors.affiliation: Department of Cardiology, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Farahmand
authors.affiliation: 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.
authors.forename: Catherine
authors.initials: C
authors.lastname: Rücker-Martin
authors.affiliation: Faculté de Médecine, Université Pierre et Marie Curie, Sorbonne University, INSERM UMR_S1166, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Dilanian
authors.affiliation: Institute of Cardiometabolism and Nutrition, Paris, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Fradet
authors.affiliation: INSERM U_955, Département Hospitalo-Universitaire Ageing-Thorax-Vessels-Blood, Département de Physiologie, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Creteil, France.
authors.forename: Daigo
authors.initials: D
authors.lastname: Sawaki
authors.affiliation: INSERM U_955, Département Hospitalo-Universitaire Ageing-Thorax-Vessels-Blood, Département de Physiologie, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Creteil, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Derumeaux
authors.affiliation: Faculté de Médecine, Université Pierre et Marie Curie, Sorbonne University, INSERM UMR_S1166, Paris, France.|Department of Cardiology, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: LePrince
authors.affiliation: Faculté de Médecine, Université Pierre et Marie Curie, Sorbonne University, INSERM UMR_S1166, Paris, France.|Institute of Cardiometabolism and Nutrition, Paris, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
authors.affiliation: Faculté de Médecine, Université Pierre et Marie Curie, Sorbonne University, INSERM UMR_S1166, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dugail
authors.affiliation: Faculté de Médecine La Timone, Université Aix-Marseille, INSERM UMR_910, Marseille, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Puceat
authors.affiliation: Faculté de Médecine, Université Pierre et Marie Curie, Sorbonne University, INSERM UMR_S1166, Paris, France; stephane.hatem@upmc.fr.|Institute of Cardiometabolism and Nutrition, Paris, France.
authors.forename: Stéphane N
authors.initials: SN
authors.lastname: Hatem
mesh_terms: D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis / Q000502:physiology*; D000273:Adipose Tissue / Q000378:metabolism*; D000368:Aged; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002478:Cells, Cultured; D059305:Diet, High-Fat; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000378:metabolism; D010496:Pericardium / Q000166:cytology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D011518:Proto-Oncogene Proteins; C491119:WNT10B protein, human; D051153:Wnt Proteins; D051176:beta Catenin; D009320:Atrial Natriuretic Factor
keywords: atrial natriuretic peptide; cGMP; epicardial adipose tissue; epicardial progenitors