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

ABSTRACT: 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.A dietary history and paired serum and liver tissue were obtained from patients with evidence of biopsy-proven NAFLD (n=49) without cirrhosis and controls (n=24) matched for gender, age (+/-5 years), and body mass index (+/-3 points).Consumption of fructose in patients with NAFLD was nearly 2- to 3-fold higher than controls [365 kcal vs 170 kcal (p<0.05)]. In patients with NAFLD (n=6), hepatic mRNA expression of fructokinase (KHK), an important enzyme for fructose metabolism, and fatty acid synthase, an important enzyme for lipogenesis were increased (p=0.04 and p=0.02, respectively). In an AML hepatocyte cell line, fructose resulted in dose-dependent increase in KHK protein and activity.The pathogenic mechanism underlying the development of NAFLD may be associated with excessive dietary fructose consumption.

SUBMITTER: Ouyang X

PROVIDER: S-EPMC2423467 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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

Ouyang Xiaosen X Cirillo Pietro P Sautin Yuri Y McCall Shannon S Bruchette James L JL Diehl Anna Mae AM Johnson Richard J RJ Abdelmalek Manal F MF

Journal of hepatology 20080310 6

<h4>Background/aims</h4>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 ...[more]

PMID: 18395287

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Project description:The role of nutrition and diet in the development of non-alcoholic fatty liver disease (NAFLD) is still not fully understood. In the present study, we determined if dietary pattern and markers of intestinal permeability differ between overweight children with and without NAFLD. In addition, in a feasibility study, we assessed the effect of a moderate dietary intervention only focusing on nutrients identified to differ between groups on markers of intestinal barrier function and health status. Anthropometric data, dietary intake, metabolic parameters, and markers of inflammation, as well as of intestinal permeability, were assessed in overweight children (n = 89, aged 5⁻9) and normal-weight healthy controls (n = 36, aged 5⁻9). Sixteen children suffered from early signs of NAFLD, e.g., steatosis grade 1 as determined by ultrasound. Twelve children showing early signs of NAFLD were enrolled in the intervention study (n = 6 intervention, n = 6 control). Body mass index (BMI), BMI standard deviation score (BMI-SDS), and waist circumference were significantly higher in NAFLD children than in overweight children without NAFLD. Levels of bacterial endotoxin, lipopolysaccharide-binding protein (LBP), and proinflammatory markers like interleukin 6 (IL-6) and tumor necrosis factor α (TNFα) were also significantly higher in overweight children with NAFLD compared to those without. Total energy and carbohydrate intake were higher in NAFLD children than in those without. The higher carbohydrate intake mainly resulted from a higher total fructose and glucose intake derived from a significantly higher consumption of sugar-sweetened beverages. When counseling children with NAFLD regarding fructose intake (four times, 30⁻60 min within 1 year; one one-on-one counseling and three group counselings), neither alanine aminotransferase (ALT) nor aspartate aminotransferase (AST) activity in serum changed; however, diastolic blood pressure (p < 0.05) and bacterial endotoxin levels (p = 0.06) decreased markedly in the intervention group after one year. Similar changes were not found in uncounseled children. Our results suggest that a sugar-rich diet might contribute to the development of early stages of NAFLD in overweight children, and that moderate dietary counseling might improve the metabolic status of overweight children with NAFLD.

Project description:BackgroundNut consumption has been associated with reduced inflammation, insulin resistance, and oxidative stress. However, the influence on the prevalence and severity of non-alcoholic fatty liver disease (NAFLD) has yet to be evaluated.Methods4655 subjects were included as part of a colorectal carcinoma screening program (SAKKOPI) between 07/2010 and 07/2019 and analyzed 2020. Patients were characterized using biochemical and metabolic parameters, as well as a detailed questionnaire on dietary habits. The diagnosis of NAFLD was established using abdominal ultrasound. Consumption of nuts was graded as: no consumption or <1 time/week, 1-6 times/week, 1 time/day and ≥2 times/day.ResultsMean age was 58.5±9.8years with a mean BMI of 26.5±4.7kg/m2. 2058 (44.2%) patients suffered from the metabolic syndrome, 2407 (51.6%) had arterial hypertension, 2287 (49.1%) showed prediabetes/diabetes, 1854 (39.4%) had dyslipidemia and 1984 patients (43.5%) were diagnosed with NAFLD. Prevalence of metabolic syndrome (1219 [48.7%] vs. 605 [40.2%] vs. 189 [37.4%] vs. 45 [31.7%], p<0.001) and NALFD (1184 [48.1%] vs. 594 [40.7%] vs. 158 [31.7%] vs. 48 [34.0%], p<0.001). On multivariable logistic regression analysis adjusting for potential confounders and dietary patterns, nut consumption ≥1time/day was inversely associated with NAFLD in the overall cohort (adjusted Odds ratio[aOR]: 0.719 [95%CI:0.558-0.926], p = 0.011). However, following subgroup analysis, this inverse association was only confirmed in male patients (aOR: 0.589 [95%CI: 0.411-0.844], p = 0.004) but not in females (aOR: 0.886 [95%CI: 0.616-1.275], p = 0.515). Moreover, patients who consumed nuts 1-6 times/week had a significantly lower prevalence of advanced fibrosis (Fib-4 score >2.67: aOR: 0.551 [95%CI: 0.338-0.898], p = 0.017; Forns-Index >6.9: aOR: 0.585 [95%CI: 0.402-0.850], p = 0.005).ConclusionsNut consumption might exert beneficial effects on the prevalence of NAFLD in males. The negative association with advanced fibrosis warrants further investigation.

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

Publications

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

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