title: Human epicardial adipose tissue induces fibrosis of the atrial myocardium through the secretion of adipo-fibrokines.
abstract: OBJECTIVE
  Recent studies have reported a relationship between the abundance of epicardial adipose tissue (EAT) and the risk of cardiovascular diseases including atrial fibrillation (AF). However, the underlying mechanisms are unknown. The aim of this study was to examine the effects of the secretome of human EAT on the histological properties of the myocardium.
  
  
  RESULTS
  Samples of EAT and subcutaneous adipose (SAT), obtained from 39 patients undergoing coronary bypass surgery, were analysed and tested in an organo-culture model of rat atria to evaluate the fibrotic properties of human fat depots. The EAT secretome induced global fibrosis (interstitial and peripheral) of rat atria in organo-culture conditions. Activin A was highly expressed in EAT compared with SAT and promoted atrial fibrosis, an effect blocked using neutralizing antibody. In addition, Activin A levels were enhanced in patients with low left-ventricular function. In sections of human atrial and ventricular myocardium, adipose and myocardial tissues were in close contact, together with fibrosis.
  
  
  CONCLUSIONS
  This study provides the first evidence that the secretome from EAT promotes myocardial fibrosis through the secretion of adipo-fibrokines such as Activin A.
authors.affiliation: Institute of Cardiometabolism and Nutrition, Paris, France INSERM, UMR_S 872, Team 7 Nutriomique, Paris, France Université Pierre et Marie Curie-Paris 6, Cordeliers Research Center, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Venteclef
authors.affiliation: Institute of Cardiometabolism and Nutrition, Paris, France INSERM, UMR_S 872, Team 7 Nutriomique, Paris, France Université Pierre et Marie Curie-Paris 6, Cordeliers Research Center, Paris, France.
authors.forename: Valeria
authors.initials: V
authors.lastname: Guglielmi
authors.affiliation: Institute of Cardiometabolism and Nutrition, Paris, France Université Pierre et Marie Curie-Paris 6, Cordeliers Research Center, Paris, France Université Pierre et Marie Curie-Paris 6, INSERM UMR_S956, Paris, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Balse
authors.affiliation: Institute of Cardiometabolism and Nutrition, Paris, France INSERM, UMR_S 872, Team 7 Nutriomique, Paris, France Université Pierre et Marie Curie-Paris 6, Cordeliers Research Center, Paris, France Heart and metabolism division, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris Faculté de Médecine, INSERM NORT UMR 1062, INRA1260, Aix Marseille Université, Marseille, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Gaborit
authors.affiliation: Institute of Cardiometabolism and Nutrition, Paris, France INSERM, UMR_S 872, Team 7 Nutriomique, Paris, France Université Pierre et Marie Curie-Paris 6, Cordeliers Research Center, Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cotillard
authors.affiliation: Institute of Cardiometabolism and Nutrition, Paris, France Université Pierre et Marie Curie-Paris 6, Cordeliers Research Center, Paris, France Université Pierre et Marie Curie-Paris 6, INSERM UMR_S956, Paris, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Atassi
authors.affiliation: Institute of Cardiometabolism and Nutrition, Paris, France Heart and metabolism division, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris.
authors.forename: Julien
authors.initials: J
authors.lastname: Amour
authors.affiliation: Institute of Cardiometabolism and Nutrition, Paris, France Heart and metabolism division, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris.
authors.forename: Pascal
authors.initials: P
authors.lastname: Leprince
authors.affiliation: Faculté de Médecine, INSERM NORT UMR 1062, INRA1260, Aix Marseille Université, Marseille, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Dutour
authors.affiliation: Institute of Cardiometabolism and Nutrition, Paris, France INSERM, UMR_S 872, Team 7 Nutriomique, Paris, France Université Pierre et Marie Curie-Paris 6, Cordeliers Research Center, Paris, France Heart and metabolism division, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris stephane.hatem@upmc.fr karine.clement@psl.aphp.fr.
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
authors.affiliation: Institute of Cardiometabolism and Nutrition, Paris, France Université Pierre et Marie Curie-Paris 6, Cordeliers Research Center, Paris, France Université Pierre et Marie Curie-Paris 6, INSERM UMR_S956, Paris, France Heart and metabolism division, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris stephane.hatem@upmc.fr karine.clement@psl.aphp.fr.
authors.forename: Stéphane N
authors.initials: SN
authors.lastname: Hatem
mesh_terms: D028341:Activins / Q000378:metabolism / Q000502:physiology; D054392:Adipokines / Q000378:metabolism* / Q000502:physiology; D000273:Adipose Tissue / Q000502:physiology*; D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism / Q000473:pathology; D064752:Atrial Remodeling / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005355:Fibrosis / Q000209:etiology / Q000473:pathology; D006325:Heart Atria / Q000473:pathology; D006801:Humans; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism / Q000502:physiology; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D050151:Subcutaneous Fat / Q000502:physiology
chemical_list: D054392:Adipokines; C422405:activin A; D028341:Activins; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8
keywords: Activin A; Atrial fibrillation; Atrial fibrosis; Epicardial adipose tissue; Myocardial fibrosis