Impacts of a high-fat diet on the metabolic profile and phenotype of atrial myocardium in mice
Metabolic diseases, such as obesity, or diabetes are risk factors for atrial fibrillation (AF), the most common cardiac arrhythmia in clinical practice. Thus, each increase in body mass index is associated with a 4% increase in AF risk. There is also a correlation between the duration of diabetes mellitus, the level of dysglycaemia and the risk of AF. If there is a common ground between AF and metabolic diseases, age, high blood pressure, atherosclerosis, there is probably also a direct impact on the heart of metabolic diseases.
Nadine Suffee of Professor Stéphane Hatem’s team (UMRS1166 cardiovascular and metabolic diseases) studied the consequences of a high-fat diet on the atrial myocardium and on the formation of AF substrate.
Method
Mice were fed a high-fat diet (60% fat) for 4 months and compared to a control group of mice fed a low-fat diet)
An unbiased mass spectroscopic analysis of the atrial myocardial metabolome and lipidome was performed, and then different strategies were used to characterize the atrial phenotype, including measurement of mitochondrial respiration and analysis of the electrophysiology of atrial myocytes studied by the patch clamp technique
Results
Thus, there is a shift in oxidative metabolism in the atria of mice on a high-fat diet toward the predominance of mitochondrial β-oxidation and the accumulation of long-chain lipids.
This metabolic remodeling is accompanied by changes in mitochondrial respiration measured ex vivo in atrial trabeculae and by shortening of action potential duration, an arrhythmogenic mechanism of AF, related to abnormal activation of ATP-dependent potassium channels in atrial myocytes. The activation of these repolarizing channels is the probable consequence of the lower energy efficiency of the metabolism of myocytes from obese mice. This is associated with increased expression of adipogenesis genes, accumulation of WT especially in the atrioventricular groove, and infiltration of the atrial myocardium by lymphocytes and monocytes/macrophages.
This study is the first demonstration of the role of diet on the atrial phenotype and AF substrate formation. Results show the role played by the balance between use and storage of fatty acids in the acquisition of an adipogenic and inflammatory profile of the atria. The study has lead to the identification of new mechanisms that link metabolism and myocardium: lipid elongation, activation of K-ATP channels, recruitment of immunoinflammatory cells.
