Whether fructose alone can cause NAFLD or if it serves only as a contributor when consumed excessively in the setting of insulin resistance, positive this website energy balance, and sedentary lifestyle is unknown. Sufficient evidence exists to support clinical recommendations that fructose intake be limited through decreasing foods and drinks high in added (fructose-containing) sugars. (HEPATOLOGY 2013;57:2525–2531) Nonalcoholic fatty liver disease (NAFLD) is a chronic, obesity-associated

liver disease that has become the most common liver disease affecting adults and children. The role of fructose in inducing NAFLD has been a critical, pervasive question, in part because the prevalence of NAFLD increased in parallel to a rapid rise in fructose consumption.1, 2 NAFLD is closely tied to hepatic insulin resistance and has been suggested to be the hepatic manifestation of the metabolic syndrome.3 As discussed below, the link between insulin resistance, visceral adiposity, and hepatic steatosis may explain how fructose contributes to NAFLD. The prevalence of NAFLD differs markedly by race and ethnicity,

raising the possibility of specific genetic susceptibilities and environmental (particularly dietary) effects. In the U.S., Mexican American obese children have the highest prevalence4, 5 and African American children seem relatively protected, despite Lumacaftor solubility dmso their high prevalence of obesity and insulin resistance.4, 6 These prevalence differences can also be seen among adult populations.7 A concerning concomitant of NAFLD is the association of NAFLD with increased cardiovascular disease risk. Natural Cyclooxygenase (COX) history studies of adults with NAFLD demonstrate that cardiovascular disease (CVD) is a substantial long-term risk,8-10 perhaps exceeding risk of death from cirrhosis.11 The association of CVD and NAFLD begins early, as children with NAFLD already have increased carotid intima media thickness (cIMT).12, 13 cIMT, carotid intima media thickness; CVD, cardiovascular disease; DNL, de novo lipogenesis;

Eh, redox potential; FFA, free fatty acid; GSH, glutathione; HDL, high density lipoprotein; LDL, low density lipoprotein; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; NHANES, National Health and Nutrition Examination Survey; ROS, reactive oxygen species; VAT, visceral adipose tissue; VLDL, very low density lipoprotein. A healthy liver generally does not store triglycerides in substantial amounts (normal typically defined as <5.5% fat fraction). Steatosis results from an imbalance between import, synthesis, utilization, and/or export of lipid in or from the liver. Defects have been demonstrated in several of these areas of lipid metabolism. Donnelly et al.14 evaluated the source of fat deposited in the liver in NAFLD and demonstrated that plasma free fatty acids (FFA) returning to the liver represented greater than half of the triglycerides stored in the fasted state (50%-70%).