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

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.