Impact of Fructose Consumption on Gene Expression: Role of miRNAs

Abstract

The metabolic syndrome (MS), a group of symptoms including elevated blood pressure and plasma fasting glucose, dyslipidemia, and obesity, has been on the rise, reaching a prevalence of 36% in the US. In proportion is an increase of fructose in soft drinks in the form of high-fructose corn syrup. MS significantly increases the risk of cardiovascular disease, and we have previously shown that FC disrupts the regulation of O2 consumption in the heart by lowering NO bioavailability through the generation of superoxide. Presently, we explored the molecular effects of FC. SD rats were fed a normal or a 60% fructose diet for 21 days. mRNA microarray analysis of cardiac tissue revealed significant changes in 238 genes (p<0.05, fold change at least ±1.5), including upregulation of the nuclear receptor Pparα, cholesterol transporter caveolin 1, and endothelin receptor B, and downregulation of Mrpl1 2, a mitochondrial ribosomal protein, and Atp5S, which encodes a subunit of mitochondrial ATP synthase. miRNA microarray analysis showed corresponding downregulation of miRNAs associated with upregulated genes and vice versa, including upregulation of miR126, a regulator of angiogenesis, and miR21, which is significantly upregulated in heart failure (downregulation of protein). Conclusion FC triggers gene expression changes in the heart with involvement of miRNAs, suggesting an underlying mechanism behind the effects of FC.