10.5061/DRYAD.Z612JM6CW
Suffee, Nadine
0000-0001-9277-5089
Institute of Cardiometabolism And Nutrition
Baptista, Elodie
Institute of Cardiometabolism And Nutrition
Piquereau, Jérome
University of Paris-Saclay
Ponnaiah, Maharajah
Institute of Cardiometabolism And Nutrition
Doisne, Nicolas
Institute of Cardiometabolism And Nutrition
Ichou, Farid
Institute of Cardiometabolism And Nutrition
Lhomme, Marie
Institute of Cardiometabolism And Nutrition
Pichard, Camille
Institute of Cardiometabolism And Nutrition
Galand, Vicent
Institute of Cardiometabolism And Nutrition
Mougenot, Nathalie
Sorbonne University
Dilanian, Gilles
Institute of Cardiometabolism And Nutrition
Lucats, Laurence
Sanofi-Aventis R&D
Balse, Elise
Institute of Cardiometabolism And Nutrition
Mericskay, Mathias
University of Paris-Saclay
Le Goeff, Wilfried
Institute of Cardiometabolism And Nutrition
Hatem, Stéphane N
Institute of Cardiometabolism And Nutrition
Impacts of a high fat diet on the metabolic profile and the phenotype of
atrial myocardium in mice
Dryad
dataset
2021
FOS: Medical and health sciences
2021-11-09T00:00:00Z
2021-11-09T00:00:00Z
en
266417 bytes
4
CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
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 favoring the formation of the substrate of
AF. Methods & 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 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. Action potentials were short duration and sensitive to
the K-ATPdependent 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
remodeling of the atrial myocardium of mice that become vulnerable to AF.
Translational perspective: Understanding the link between metabolic
diseases and atrial fibrillation is of major importance. One hypothesis
claims that, in addition to shared co-morbidities, metabolic disorders
favor the substrate of atrial fibrillation. Here we show that after
prolonged high fat diet, the atrial myocardium becomes adipogenic,
inflamed and vulnerable to atrial fibrillation. This tissue remodeling
appears to result from an unbalance between uptake and oxidation of fatty
acid resulting in long-chain lipid storage, activation metabolic-sensitive
potassium channel and action potential shortening. Therefore, diet appears
to be an important link between metabolic disorders and atrial
fibrillation.