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Background/Objectives:To examine lifestyle patterns (diet, physical activity, energy expenditure) and metabolic variables (insulin resistance, oxidative stress, inflammation) in children with fatty liver detected by sonography.Subjects/Methods:Body composition (fat-free mass, body mass index-z), waist circumference (WC), dietary intake and energy expenditure were determined in 38 patients (ages 5–19 years) with fatty liver in whom specific causative liver disorders had been excluded. Laboratory investigations included liver biochemistries, C-reactive protein, tumor necrosis factor-α, glutathione peroxidase, vitamin E, and erythrocyte-glutathione.Results:In all, 36 of 38 children were overweight/obese; 37 had WC indicative of abdominal obesity. They displayed fasting hyperinsulinemia (n=15), hypertriglyceridemia (n=14), and hypoadiponectinemia (5.5±1.9 s.d. μg/ml; n=23) and insulin resistance (homeostasis model of insulin resistance (HOMA-IR)>3; n=21). Alanine aminotransferase (ALT) was elevated in 28 (43–556 U/l; median=56). Some inflammatory markers were elevated, whereas antioxidants were decreased. Diet was characterized by high saturated-, low polyunsaturated-fat, high fructose and sucrose intakes. Fructose intake was independently associated with insulin resistance and decreased serum adiponectin, regardless of serum ALT (P<0.05). Low and subnormal intakes of omega-3 fatty acids (C20:5 (n-3) and C22:6 (n-3)) were associated with abnormal serum ALT (P=0.006) and elevated HOMA-IR (P=0.01). Findings were similar in children 11 and >11 years old. Physical activity was low in both age groups.Conclusions:Children with fatty liver detected sonographically have metabolic features of non-alcoholic fatty liver disease. Their diets are high in fructose and low in polyunsaturated fatty acid. Their activity patterns are sedentary. These lifestyle features may contribute to liver damage and can be a focus for therapeutic intervention. [ABSTRACT FROM AUTHOR]

The central pathways of metabolism include glycolysis and gluconeogenesis, fatty acid synthesis and beta-oxidation, the citric acid cycle and ureagenesis. Because these pathways intersect, changes in one pathway, due to inborn error or disease, affect pathways that may seem remote from the initial metabolic defect. These metabolic interrelationships also present difficulties for isotopic studies, because once carbon derived from isotopic tracers is introduced into metabolism it is extensively recycled. The use of multiple labeled (especially uniformly C-labeled ([U-C]), metabolic tracers, in conjunction with mass isotopomer distribution analysis of mass and nuclear magnetic spectra, has enabled the development of methods that resolve some of these difficulties. Suitable choices of tracers and analytes allow the simultaneous measurement of multiple pathways and, importantly, their kinetic interrelationships. We illustrate three uses of the technique: (1) the unequivocal determination of tracee fluxes; (2) the quantification of biosynthetic pathways; and (3) the dissection, in vivo, of the citric acid (Krebs) cycle. In each case, different combinations of [U-C]tracer and metabolic end product have revealed metabolic phenomena that otherwise would remain unidentified. A particularly striking, and unexpected, observation that has emerged from recent studies using the technique, suggests that the key dehydrogenase reactions in the Krebs cycle may be reversible. Although this approach is of relatively recent development, it has already given a number of novel insights into the organization of the central metabolic pathways. It should provide a powerful method of investigating the metabolic impact of genetic disease and provide invaluable support of the assessment of new therapeutic interventions. [ABSTRACT FROM AUTHOR]