High fructose diet and its effect on gene regulation in rat heart

Abstract

High fructose consumption (FC) has been thought to be a contributing cause of insulin resistance, obesity, elevated LDL cholesterol and triglycerides, leading to metabolic and cardiovascular diseases. The effects of 21 days of a 60% purified fructose diet on gene expression, using Affymetric Rat Arrays, were investigated in cardiac tissues of female SD rats. Hemodynamic measurements showed significant increases in mean arterial pressure and insulin levels in FC. NO bioactivity was impaired by FC and this effect was reversed by tiron, which scavenges superoxide. These data suggest a role of superoxide in the heart during FC. The array data revealed 235 genes significantly regulated (p<0.05, ± 1.5 fold) in FC. The up regulated genes (n= 123) included caveolin 1 (limits NO production), PDE5A (increases NO breakdown), glucose‐fructose oxidoreductase, peroxisome proliferator activated receptor alpha, peroxisomal biogenesis factor 11 alpha, phosphatidylinositol 5‐kinase, granzyme A and stoning 2 (both shown to be expressed in diabetes). The down regulated genes (n= 112) included glucose‐6‐phosphate dehydrogenase, insulin‐like growth factor 2, N‐acetyltransferase 14, glutathione S‐transferase, ATPase, mitochondria ribosomal protein and UCP2. These results indicate that high fructose intake has a dramatic effect on the heart by regulating a large number of metabolic and energy producing genes.Supported by HL‐PO1‐43023 & HL 50142.