Fructose induces the inflammatory molecule ICAM-1 in endothelial cells.
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-kappaB 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.
Glushakova
Olena
O
Division of Nephrology, Hypertension and Transplantation, University of Florida, P.O. Box 100224, Gainesville, FL 32610-0224, USA.
Kosugi
Tomoki
T
Roncal
Carlos
C
Mu
Wei
W
Heinig
Marcelo
M
Cirillo
Pietro
P
Sánchez-Lozada
Laura G
LG
Johnson
Richard J
RJ
Nakagawa
Takahiko
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology; D002478:Cells, Cultured; D004040:Dietary Carbohydrates / Q000009:adverse effects*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D005632:Fructose / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004040:Dietary Carbohydrates; D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1; D005632:Fructose; D009569:Nitric Oxide; D000255:Adenosine Triphosphate