Fructose and uric acid: is there a role in endothelial function?

Abstract

Population level data support that consumption of fructose and fructose-based sweeteners has dramatically increased and suggest that high dietary intake of fructose is an important factor in the development of the cardiorenal metabolic syndrome (CRS). The CRS is a constellation of cardiac, kidney and metabolic disorders including insulin resistance, obesity, metabolic dyslipidemia, high blood pressure, and evidence of early cardiac and kidney disease. The consequences of fructose metabolism may result in intracellular ATP depletion, increased uric acid production, oxidative stress, inflammation, and increased lipogenesis, which are associated with endothelial dysfunction. Endothelial dysfunction is an early manifestation of vascular disease and a driver for the development of CRS. A better understanding of fructose overconsumption in the development of CRS may provide new insights into pathogenesis and future therapeutic strategies.

Fig. 1

Proposed roles of fructose and uric acid in the development of endothelial cell dysfunction and CRS. Fructose intake increases uric acid production, oxidative stress, inflammation, and de novo lipogenesis, subsequently results in endothelial cell dysfunction, whereas endothelial dysfunction further aggravates fructose-induced and uric acid-induced CRS. Abbreviations: RAS renin-angiotensin-aldosterone system; ROS reactive oxygen species; IL interleukin; TNF tumor necrosis factor; NO nitric oxide; ONOO⁻, peroxynitrite; PAI plasminogen activator inhibitor; TPA tissue plasminogen activator; ET-1 endothelin-1; Ang II angiotensin II; TxA2 thromboxane A2