This review paper discusses mechanisms that could link fructose intake with the developement of insulin resistance and other components of the metabolic syndrome. Chronic fructose consumption generates disturbances in multiple tissues, including liver, adipose tissue, the gastrointestinal system and the central nervous system. More specifically, it was reported that fructose consumption may promote lipid deposition in intra-abdominal (visceral) adipose tissue, particularly in men. This accumulation of adipose tissue eventually leads to impaired insulin signalling and an increase in lipolysis which contribute to the delivery of free fatty acids to the liver. The effects of fructose on the liver include activation of sterol regulatory element-binding proteins, which activates genes involved in de novo lipogenesis. These fatty acids that can then be incorporated into hepatic triglycerides which are associated with increased VLDL synthesis and secretion and apolipoprotein B accumulation in the hepatic endoplasmic reticulum therefore causing endoplasmic reticulum stress. Fructose administration was reported to decrease peroxisome proliferator-activated receptor (PPAR)-a activity compromising fatty acid oxidation in mitochondria. Fructose also induces disturbances in the clearance of circulating lipids and lipoproteins by increasing apolipoprotein CIII production and impairing triglyceride hydrolysis. Leptin resistance as well as activation of inflammatory pathways are effects observed with fructose feeding. The central effects of fructose consist of impaired satiety and increased lactate production, an energy substrate for neurons. Additional emerging complications to consider following chronic fructose consumption are altered gut integrity and intestinal inflammation. This constellation of abnormalities contributes to the development of multiple components of the metabolic syndrome. Further studies are necessary to clarify the metabolic consequences of fructose intake in humans.
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