Effect of ABT-335 (fenofibric acid) on meal-induced oxidative stress in patients with metabolic syndrome.

OBJECTIVE: Examine the effect of ABT-335 (fenofibric acid) on postprandial lipemia and susceptibility of plasma lipoproteins to Cu(++)-mediated oxidation in patients with metabolic syndrome. METHODS AND RESULTS: This is a randomized double-blind, placebo-controlled study with cross-over and includes a 4-week wash-out period between the two treatment periods. At the end of each 8-week treatment period, subjects were challenged with a standardized mixed meal followed by blood collection over the ensuing 6 h. Plasma lipoproteins were isolated by a combination of ultracentrifugation and FPLC for the continuous monitoring of conjugated dienes formation as an assessment of oxidative susceptibility. Fasting plasma TG was reduced by 20% (p < 0.0002) and there was a modest reduction in hsCRP (6.1%, p < 0.06). There was no change in either HDLc or LDLc in these subjects. Postprandial lipemia was reduced with ABT-335 as demonstrated by a 28.5% reduction (p < 0.0005) in incremental area under the curve for TG during the 6-h period after the meal challenge. Lag times for both fasting LDL (+16%) and postprandial LDL (+28%) were increased with the ABT-335 therapy, suggestive of reduced oxidative susceptibility. Co-incubation with autologous HDL did not reduced LDL oxidative susceptibility in these patients. CONCLUSION: ABT-335 therapy reduced fasting and postprandial triglycerides in patients with metabolic syndrome. Autologous HDL may be dysfunctional in these patients as co-incubation with HDL failed to reduce oxidative susceptibility of LDL. During ABT-335 therapy, LDL was less susceptible to Cu(++)-mediated oxidative modification, in spite of the lack of changes in LDLc levels.

Children with NAFLD are more sensitive to the adverse metabolic effects of fructose beverages than children without NAFLD.

CONTEXT: Dietary fructose induces unfavorable lipid alterations in animal models and adult studies. Little is known regarding metabolic tolerance of dietary fructose in children. OBJECTIVES: The aim of the study was to evaluate whether dietary fructose alters plasma lipids in children with nonalcoholic fatty liver disease (NAFLD) and in healthy children. DESIGN AND SETTING: We performed a 2-d, crossover feeding study at the Inpatient Clinical Interaction Site of the Atlanta Clinical and Translational Science Institute at Emory University Hospital. PARTICIPANTS AND INTERVENTION: Nine children with NAFLD and 10 matched controls without NAFLD completed the study. We assessed plasma lipid levels over two nonconsecutive, randomly assigned, 24-h periods under isocaloric, isonitrogenous conditions with three macronutrient-balanced, consecutive meals and either: 1) a fructose-sweetened beverage (FB); or 2) a glucose beverage (GB) being consumed with each meal. MAIN OUTCOME MEASURES: Differences in plasma glucose, insulin, triglyceride, apolipoprotein B, high-density lipoprotein cholesterol, and nonesterified free fatty acid levels were assessed using mixed models and 24-h incremental areas under the time-concentration curve. RESULTS: After FB, triglyceride incremental area under the curve was higher vs. after GB both in children with NAFLD (P = 0.011) and those without NAFLD (P = 0.027); however, incremental response to FB was greater in children with NAFLD than those without NAFLD (P = 0.019). For all subjects, high-density lipoprotein cholesterol declined in the postprandial and overnight hours with FB, but not with GB (P = 0.0006). Nonesterified fatty acids were not impacted by sugar but were significantly higher in NAFLD. CONCLUSIONS: The dyslipidemic effect of dietary fructose occurred in both healthy children and those with NAFLD; however, children with NAFLD demonstrated increased sensitivity to the impact of dietary fructose.