Carbohydrate intake and nonalcoholic fatty liver disease: fructose as a weapon of mass destruction

Excessive accumulation of triglycerides (TG) in liver, in the absence of significant alcoholconsumption is nonalcoholic fatty liver disease (NAFLD). NAFLD is a significant risk factor for developingcirrhosis and an independent predictor of cardiovascular disease. High fructose corn syrup (HFCS)-containingbeverages were associated with metabolic abnormalities, and contributed to the development of NAFLD inhuman trials. Ingested carbohydrates are a major stimulus for hepatic de novo lipogenesis (DNL) and aremore likely to directly contribute to NAFLD than dietary fat. Substrates used for the synthesis of newlymade fatty acids by DNL are primarily glucose, fructose, and amino acids. Epidemiological studies linkedHFCS consumption to the severity of fibrosis in patients with NAFLD. New animal studies providedadditional evidence on the role of carbohydrate-induced DNL and the gut microbiome in NAFLD. Theexcessive consumption of HFCS-55 increased endoplasmic reticulum stress, activated the stress-relatedkinase, caused mitochondrial dysfunction, and increased apoptotic activity in the liver. A link between dietaryfructose intake, increased hepatic glucose transporter type-5 (Glut5) (fructose transporter) gene expressionand hepatic lipid peroxidation, MyD88, TNF-α levels, gut-derived endotoxemia, toll-like receptor-4, andNAFLD was reported. The lipogenic and proinflammatory effects of fructose appear to be due to transientATP depletion by its rapid phosphorylation within the cell and from its ability to raise intracellular andserum uric acid levels. However, large prospective studies that evaluated the relationship between fructoseand NAFLD were not performed yet.