Fructose consumption as a risk factor for non-alcoholic fatty liver disease

Abstract

BACKGROUND/AIMS-While the rise in non-alcoholic fatty liver disease (NAFLD) parallels the increase in obesity and diabetes, a significant increase in dietary fructose consumption in industrialized countries has also occurred. The increased consumption of high fructose corn syrup, primarily in the form of soft-drinks, is linked with complications of the insulin resistance syndrome. Furthermore, the hepatic metabolism of fructose favors de novo lipogenesis and ATP depletion. We hypothesize that increased fructose consumption contributes to the development of NAFLD.

Toll-like receptor 4 is involved in the development of fructose-induced hepatic steatosis in mice

“…Rather, our results suggest that an increased intestinal translocation of bacterial endotoxin and subsequent activation of Kupffer cells through a TLR-4-dependent mechanism mediated through MyD88-dependent signaling pathways may also partially add or even enhance the development of this liver disease (e.g., through causing insulin resistance). These findings are also in line with results of recent human studies 6,7 suggesting that in patients with NAFLD, both dietary fructose intake and plasma endotoxin levels are elevated in comparison to controls. However, additional studies will be necessary to further explore underlying mechanisms and possible resulting therapeutic strategies (e.g., fructose avoidance therapy, treatment with antibiotics).…”

“…4,5 Furthermore, it has recently been shown that in patients with NAFLD (e.g., with simple steatosis and steatohepatitis with begin-ning fibrosis) intake of fructose is markedly higher than in controls. 6,7 In line with these findings it has been shown in animal studies that an increased consumption of fructose (e.g., up to 60% of daily calories derived from fructose) may result in hepatic steatosis accompanied by insulin resistance, elevated plasma triglyceride levels, and oxidative stress in the liver. [8][9][10][11] In addition, we recently showed that even the early stages of fructose-induced NAFLD (e.g., steatosis) are associated with an increased intestinal translocation of bacterial endotoxin, formation of 4-hydroxynonenal adduct formation, and expression of tumor necrosis factor alpha (TNF␣) in the liver.…”

Coenzyme Q10 supplementation lowers hepatic oxidative stress and inflammation associated with diet-induced obesity in mice

“…Those metabolic disturbances have been associated with i.e. hypertriglyceridemia and steatosis, linked to an increased de novo lipogenesis [12,13], modification of the activity of enzymes involved in hepatic glucose metabolism and glucose uptake pathways [14,15] and activation of NADPH oxidase pathway [11].…”

Toll-like receptor 4: A starting point for proinflammatory signals in fatty liver disease

“…In particular, a recent work 4 demonstrates that patients with NAFLD have a significantly greater consumption of fructose than controls, and an increased hepatic expression of fructokinase messenger RNA. Although the role of TLR-4 in carbohydratedependent NAFLD has been only recently suggested by Thuy and colleagues, 5 they have pinpointed one of the potential mechanisms through which fructose could participate in NAFLD development and progression in humans: a carbohydrate-rich diet may produce ethanol when intestinal stasis favors bacterial overgrowth in the upper parts of the gastrointestinal tract.…”

“…We assessed the ability of these two indexes and of plasma cytokeratin-18 fragments (CK-18) to predict the presence of nonalcoholic fatty liver disease (NAFLD) and of nonalcoholic steatohepatitis (NASH), 1,2 respectively, and their relations to validated predictors of incident cardiovascular disease and diabetes. 3,4 To this purpose, 125 subjects (40 nondiabetic patients with biopsyproven NAFLD and 85 healthy controls) underwent an oral fat tolerance test, 5 with measurement of postprandial plasma lipid responses, and a standard oral glucose tolerance test (OGTT), whose results were elaborated by Minimal Model analysis to assess whole-body, hepatic, and muscle insulin sensitivity and indexes of pancreatic ␤-cell function (namely, CP-genic index [CGI] and Adaptation Index [AI]), as previously described. [5][6][7] Finally, circulating markers of inflammation (Creactive protein), endothelial dysfunction (E-selectin and intercellular adhesion molecule-1 [ICAM-1]) and oxidative stress (nitrotyrosine and oxidized low-density lipoproteins) were measured.…”