SAT-630 Nutritional Influences on One Carbon Metabolism Exacerbate Diabetic Cardiomyopathy and Nephropathy

Abstract Choline (Ch) exerts a key role as methyl donor in the one carbon pathway and is an essential nutrient for the optimal development and function of a number of biological systems including the cardiovascular and urinary system. Ch-deprivation has been associated with heart function impairment, insulin resistance, abnormal fat metabolism and acute kidney injury. Diabetes mellitus is a common metabolic disorder with increased prevalence in aging and diabetic patients are of higher risk to develop heart and kidney failure. This study aims to investigate the impact of dietary Ch-deprivation on cardiac and renal function in a streptozotocin (STZ) experimentally induced diabetic setting. Twenty-four male adult Wistar rats, were randomly separated into four groups: control, choline deficient through choline deficient diet (CD), STZ induced diabetic (DM) and diabetic-choline deficient (DM+CD) group. After 5 weeks of dietary intervention, echocardiographic measurements, myocardium and kidney histological examination along with Vascular Endothelial Growth Factor-A (VEGF-A165) and Kidney Injury Molecule-1 (KIM-1) immunohistochemistry expression were performed. DM+CD rats demonstrated an exacerbation of myocardial inflammation and fibrosis accompanied by preserved ejection fraction but with an increased left ventricular (LV) wall tension index and velocity and a decreased LV posterior wall thickness compared to DM group. VEGF-A165 expression both in heart and kidneys was abruptly upregulated in the CD rats with a downward trend under the diabetes mellitus entity reaching significant downregulation in the renal tissue. KIM-1 expression was significantly increased under the insult of both choline deficiency and diabetes mellitus depicting a possible synergistic, though detrimental, effect compared to each condition alone. In conclusion, five weeks of dietary choline deprivation aggravates the inflammation and fibrosis in the heart and kidneys of diabetic rats leading to organ dysfunction. The structural impairment of the choline deprived diabetic heart with evidence of stiffness and dilation of the left ventricular cavity with preserved systolic function indicates the emergence of a new distinct phenotype of cardiomyopathy that combines features of the restrictive and dilated type at the same time. Moreover, in this setting the kidney injury gets worse implying that diabetic nephropathy might establish earlier and accelerate more quickly in choline deficiency conditions.