Fructose Induces the Inflammatory Molecule ICAM-1 in Endothelial Cells

Abstract

Epidemiologic studies have linked fructose intake with the metabolic syndrome, and it was recently reported that fructose induces an inflammatory response in the rat kidney. Here, we examined whether fructose directly stimulates endothelial inflammatory processes by upregulating the inflammatory molecule intercellular adhesion molecule-1 (ICAM-1). When human aortic endothelial cells were stimulated with physiologic concentrations of fructose, ICAM-1 mRNA and protein expression increased in a time-and dosage-dependent manner, which was independent of NF-B activation. Fructose reduced endothelial nitric oxide (NO) levels and caused a transient reduction in endothelial NO synthase expression. The administration of an NO donor inhibited fructose-induced ICAM-1 expression, whereas blocking NO synthase enhanced it, suggesting that NO inhibits endothelial ICAM-1 expression. Furthermore, fructose resulted in decreased intracellular ATP; administration of exogenous ATP blocked fructose-induced ICAM-1 expression and increased NO levels. Consistent with the in vitro studies, dietary intake of fructose at physiologic dosages increased both serum ICAM-1 concentration and endothelial ICAM-1 expression in the rat kidney. These data suggest that fructose induces inflammatory changes in vascular cells at physiologic concentrations.

Endogenous Fructose Production and Fructokinase Activation Mediate Renal Injury in Diabetic Nephropathy

“…18,24 Fructose can also increase the expression of intercellular adhesion molecule-1 in vascular endothelial cells throughout the kidney. 25 In addition, selective injury to the proximal tubule can result in glomerular damage, possibly because of connecting tubule glomerular feedback in which reflex arteriolar vasodilation from tubular damage causes increases in glomerular pressure. 26,27 Interestingly, repeated proximal tubular damage has been proposed as a pathogenic mechanism in the progression of diabetic nephropathy.…”

Association of Sweetened Beverage Intake with Incident Hypertension

“…Previous cross-sectional studies have reported an association between SSB consumption and incident hypertension: Nguyen et al found a relation between intake of sodas sweetened with HFCS and hypertension in a population of adolescents, 5 and an analysis of NHANES data found an increased prevalence of hypertension among individuals consuming higher than average amounts of fructose (≥ 74 g/d) derived mostly from SSBs. 6 Because SSBs contain fructose, which in animal studies has been shown to cause renal damage, increased gastrointestinal sodium uptake, and endothelial dysfunction, [17][18][19] it was hypothesized that the HFCS in sugary beverages was responsible for the increased risk of incident hypertension. In a prospective study, however, Forman et al found no association between total fructose intake (regardless of source) and hypertension risk.…”

Beneficial effects of melatonin on serum nitric oxide, homocysteine, and ADMA levels in fructose-fed rats

“…Vascular dysfunction due to fructose-rich diet has been reported in rats. In addition, impaired endothelium-dependent relaxation has been found to occur after fructose intake in mice (Delbosc et al, 2005;Glushakova et al, 2008). There is now evidence that insulin modulates the expression of endothelial nitric oxide synthase (eNOS) and stimulates nitric oxide (NO) production, causing vasodilation.…”