Figure 3

Putative mechanisms that may link excessive fructose intake to the development of metabolic disorders in the long term. Stimulation of hepatic de novo lipogenesis may lead to the deposition of fat within the liver, which may secondarily be involved in hepatic insulin resistance. Hepatic de novo lipogenesis may also cause an increase in VLDL-TG secretion and ectopic deposition of lipids in skeletal muscle, and contribute to muscle insulin resistance through the generation of muscle lipid metabolites. Fructose metabolism in the liver increases uric acid synthesis, and the ensuing hyperuricemia can secondarily be responsible for endothelial cell dysfunction, impaired insulin-induced vasodilation and a consequent failure to increase muscle blood flow after a meal, leading to muscle insulin resistance. In addition, the metabolism of fructose in liver cells can cause the formation of reactive oxygen species (ROS), which can activate nuclear factor (NF)κB, causing inflammation-linked insulin resistance. Finally, fructose can increase the translocation of bacterial endotoxin (lipopolysaccharide (LPS)) into the portal blood, causing endotoxin-mediated stimulation of inflammation. TNF, tumor necrosis factor.