The interaction of choline and one-carbon / folate metabolism derangements on the cardiac remodeling process with or without diabetes

Abstract

Proper nutrition helps protect from illness and disease. Choline (Ch), an essential molecule of substantial importance for the optimal development and function of several biological systems, plays a crucial role in the pathway of onecarbon metabolism. On the other hand, Ch-deprivation (CD) has been linked with abnormal fat metabolism, insulin resistance, and myocardial dysfunction. The Ch-deficiency setting is an established experimental model of non-alcoholic steatohepatitis that resembles the human non-alcoholic fatty liver disease (NAFLD); a disease with constantly increasing incidence and prevalence. NAFLD, commonly associated with metabolic comorbidities such as obesity and type 2 diabetes mellitus, consists a high risk for cardiovascular disease. Experimental data of dietary CD through the administration of a Ch-deficient diet to rodents have revealed myocardial monocyte infiltration along with cardiac interstitial oedema and fibrosis, as well as a deleterious effect on cardiac valves that could lead to impaired heart mechanical properties which resemble to a restrictive pattern of cardiomyopathy characterised mainly by diastolic dysfunction. In a Ch-deprived diabetic experimental model, the diastolic heart failure has been characterized by a concentric hypertrophied myocardium, a left ventricular cavity with a thinner wall, and an increased left ventricular diastolic diameter, in addition to a left atrial dilatation that could also exert functional derangement and provoke arrhythmogenesis, thereby jeopardising cardiac output.