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Impacts of a high fat diet on the metabolic profile and the phenotype of atrial myocardium in mice

Citation

Suffee, Nadine et al. (2021), Impacts of a high fat diet on the metabolic profile and the phenotype of atrial myocardium in mice, Dryad, Dataset, https://doi.org/10.5061/dryad.z612jm6cw

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 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.