Impacts of a high-fat diet on the metabolic profile and the phenotype of atrial myocardium in mice
Nadine Suffee
(1)
,
Elodie Baptista
(1)
,
Jérôme Piquereau
,
Maharajah Ponnaiah
,
Nicolas Doisne
(1)
,
Farid Ichou
,
Marie Lhomme
(1)
,
Camille Pichard
,
Vincent Galand
,
Nathalie Mougenot
(1)
,
Gilles Dilanian
(1)
,
Laurence Lucats
,
Elise Balse
(1)
,
Mathias Mericskay
,
Wilfried Le Goff
(1, 2, 3, 4)
,
Stéphane Hatem
(1)
1
ICAN -
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
2 SU - Sorbonne Université
3 SU FM - Sorbonne Université - Faculté de Médecine
4 IHU ICAN - Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière]
2 SU - Sorbonne Université
3 SU FM - Sorbonne Université - Faculté de Médecine
4 IHU ICAN - Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière]
Nadine Suffee
- Fonction : Auteur
- PersonId : 765281
- ORCID : 0000-0001-9277-5089
Jérôme Piquereau
- Fonction : Auteur
- PersonId : 1110928
- ORCID : 0000-0002-6019-8683
- IdRef : 150086156
Maharajah Ponnaiah
- Fonction : Auteur
- PersonId : 792752
- ORCID : 0000-0001-7761-4228
Nicolas Doisne
- Fonction : Auteur
- PersonId : 772761
- ORCID : 0000-0002-6030-3869
Farid Ichou
- Fonction : Auteur
- PersonId : 184116
- IdHAL : farid-ichou
- ORCID : 0000-0001-6293-5133
- IdRef : 174096151
Camille Pichard
- Fonction : Auteur
Vincent Galand
- Fonction : Auteur
Gilles Dilanian
- Fonction : Auteur
- PersonId : 781142
- ORCID : 0000-0002-8710-8836
Laurence Lucats
- Fonction : Auteur
Elise Balse
- Fonction : Auteur
- PersonId : 1094729
- ORCID : 0000-0001-5224-9180
- IdRef : 10887110X
Mathias Mericskay
- Fonction : Auteur
- PersonId : 756432
- ORCID : 0000-0002-6779-092X
- IdRef : 158095626
Wilfried Le Goff
- Fonction : Auteur
- PersonId : 753668
- IdHAL : wilfried-le-goff
- ORCID : 0000-0002-7611-9644
- IdRef : 070753490
Résumé
Abstract Aims Obesity, diabetes, and metabolic syndromes are risk factors of atrial fibrillation (AF). We tested the hypothesis that metabolic disorders have a direct impact on the atria favouring the formation of the substrate of AF. Methods and results Untargeted metabolomic and lipidomic analysis was used to investigate the consequences of a prolonged high-fat diet (HFD) on mouse atria. Atrial properties were characterized by measuring mitochondria respiration in saponin-permeabilized trabeculae, by recording action potential (AP) with glass microelectrodes in trabeculae and ionic currents in myocytes using the perforated configuration of patch clamp technique and by several immuno-histological and biochemical approaches. After 16 weeks of HFD, obesogenic mice showed a vulnerability to AF. The atrial myocardium acquired an adipogenic and inflammatory phenotypes. Metabolomic and lipidomic analysis revealed a profound transformation of atrial energy metabolism with a predominance of long-chain lipid accumulation and beta-oxidation activation in the obese mice. Mitochondria respiration showed an increased use of palmitoyl-CoA as energy substrate. APs were short duration and sensitive to the K-ATP-dependent channel inhibitor, whereas K-ATP current was enhanced in isolated atrial myocytes of obese mouse. Conclusion HFD transforms energy metabolism, causes fat accumulation, and induces electrical remodelling of the atrial myocardium of mice that become vulnerable to AF.
Domaines
Sciences du Vivant [q-bio]Format du dépôt | Notice |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
Impacts of a high-fat diet on the metabolic profile and the phenotype of atrial myocardium in mice
|
Résumé |
en
Abstract Aims Obesity, diabetes, and metabolic syndromes are risk factors of atrial fibrillation (AF). We tested the hypothesis that metabolic disorders have a direct impact on the atria favouring the formation of the substrate of AF. Methods and results Untargeted metabolomic and lipidomic analysis was used to investigate the consequences of a prolonged high-fat diet (HFD) on mouse atria. Atrial properties were characterized by measuring mitochondria respiration in saponin-permeabilized trabeculae, by recording action potential (AP) with glass microelectrodes in trabeculae and ionic currents in myocytes using the perforated configuration of patch clamp technique and by several immuno-histological and biochemical approaches. After 16 weeks of HFD, obesogenic mice showed a vulnerability to AF. The atrial myocardium acquired an adipogenic and inflammatory phenotypes. Metabolomic and lipidomic analysis revealed a profound transformation of atrial energy metabolism with a predominance of long-chain lipid accumulation and beta-oxidation activation in the obese mice. Mitochondria respiration showed an increased use of palmitoyl-CoA as energy substrate. APs were short duration and sensitive to the K-ATP-dependent channel inhibitor, whereas K-ATP current was enhanced in isolated atrial myocytes of obese mouse. Conclusion HFD transforms energy metabolism, causes fat accumulation, and induces electrical remodelling of the atrial myocardium of mice that become vulnerable to AF.
|
Auteur(s) |
Nadine Suffee
1
, Elodie Baptista
1
, Jérôme Piquereau
, Maharajah Ponnaiah
, Nicolas Doisne
1
, Farid Ichou
, Marie Lhomme
1
, Camille Pichard
, Vincent Galand
, Nathalie Mougenot
1
, Gilles Dilanian
1
, Laurence Lucats
, Elise Balse
1
, Mathias Mericskay
, Wilfried Le Goff
1, 2, 3, 4
, Stéphane Hatem
1
1
ICAN -
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
( 542105 )
- Faculté de Médecine - 91 boulevard de l'Hôpital 75634 Paris Cedex 13
- France
2
SU -
Sorbonne Université
( 413221 )
- 21 rue de l’École de médecine - 75006 Paris
- France
3
SU FM -
Sorbonne Université - Faculté de Médecine
( 541997 )
- 4 place Jussieu - 75005 Paris
- France
4
IHU ICAN -
Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière]
( 1085123 )
- Hôpital la Pitié Salpêtrière
47-83 boulevard de l’Hôpital
75013 Paris 13
- France
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Date de publication |
2022-12-09
|
Volume |
118
|
Numéro |
15
|
Page/Identifiant |
3126-3139
|
Langue du document |
Anglais
|
Nom de la revue |
|
Projet(s) ANR |
|
Domaine(s) |
|
DOI | 10.1093/cvr/cvab367 |
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