Background & Aims Consumption of sugar is associated with obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease, and cardiovascular disease. The conversion of fructose to fat in liver (de novo lipogenesis, DNL) may be a modifiable pathogenetic pathway. We determined the effect of 9 days of isocaloric fructose restriction on DNL, liver fat, visceral fat (VAT), subcutaneous fat, and insulin kinetics in obese Latino and African American children with habitual high sugar consumption (fructose intake more than 50 g/day). Methods Children (9–18 years old; n = 41) had all meals provided for 9 days with the same energy and macronutrient composition as their standard diet, but with starch substituted for sugar, yielding a final fructose content of 4% of total kcal. Metabolic assessments were performed before and after fructose restriction. Liver fat, VAT, and subcutaneous fat were determined by magnetic resonance spectroscopy and imaging. The fractional DNL area under the curve value was measured using stable isotope tracers and gas chromatography/mass spectrometry. Insulin kinetics were calculated from oral glucose tolerance tests. Paired analyses compared change from day 0 to day 10 within each child. Results Compared with baseline, on day 10, liver fat decreased from a median of 7.2% (inter-quartile range, 2.5%–14.8%) to 3.8% (inter-quartile range, 1.7%–15.5%)(P<.001) and VAT decreased from 123 cm3 (inter-quartile range, 85–145 cm3) to 110 cm3 (inter-quartile range, 84–134 cm3) (P<.001). The DNL area under the curve decreased from 68% (inter-quartile range, 46%–83%) to 26% (inter-quartile range, 16%–37%) (P<0.001). Insulin kinetics improved (P<.001). These changes occurred irrespective of baseline liver fat. Conclusions Short-term (9 day) isocaloric fructose restriction decreased liver fat, VAT, and DNL, and improved insulin kinetics in children with obesity. These findings support efforts to reduce sugar consumption. ClinicalTrials.gov no: NCT01200043

Objective Dietary fructose is implicated in metabolic syndrome, but intervention studies are confounded by positive caloric balance, changes in adiposity, or artifactually high amounts. We determined whether isocaloric substitution of starch for sugar would improve metabolic parameters in Latino (n=27) and African-American (n=16) children with obesity and metabolic syndrome. Methods Participants consumed a diet for nine days to deliver comparable percentages of protein, fat, and carbohydrate as their self-reported diet; however, dietary sugar was reduced from 28% to 10%, and substituted with starch. Participants recorded daily weights, with calories adjusted for weight maintenance. Participants underwent dual-energy X-ray absorptiometry (DXA) and oral glucose tolerance testing (OGTT) on Days 0 and 10. Biochemical analyses were controlled for weight change by repeated measures ANCOVA. Results Reductions in diastolic BP (−5 mmHg; p=0.002), lactate (−0.3 mmol/L; p<0.001), triglyceride and LDL-cholesterol (−46% and −0.3 mmol/L; p<0.001) were noted. Glucose tolerance and hyperinsulinemia improved (p<0.001). Weight reduced by 0.9±0.2 kg (p<0.001) and fat-free mass by 0.6 kg (p=0.04). Post-hoc sensitivity analysis demonstrates that results in the subcohort that did not lose weight (n=10) were directionally consistent Conclusions Isocaloric fructose restriction improved surrogate metabolic parameters in children with obesity and metabolic syndrome irrespective of weight change.

BackgroundPolybrominated diphenyl ethers (PBDEs) are lipophilic flame retardants that bioaccumulate in humans. Child serum PBDE concentrations in California are among the highest worldwide. PBDEs may be associated with obesity by disrupting endocrine systems.ObjectiveIn this study, we examined whether pre- and postnatal exposure to the components of pentaBDE mixture was associated with childhood obesity in a population of Latino children participating in a longitudinal birth cohort study in the Salinas Valley, California.MethodsWe measured PBDEs in serum collected from 224 mothers during pregnancy and their children at 7 years of age, and examined associations with body mass index (BMI) at age 7 years.ResultsMaternal PBDE serum levels during pregnancy were associated with higher BMI z-scores in boys (BMI z-score βadjusted = 0.26; 95% CI: –0.19, 0.72) but lower scores in girls (BMI z-score βadjusted = –0.41; 95% CI: –0.87, –0.05) at 7 years of age (pinteraction = 0.04). In addition, child’s serum BDE-153 concentration (log10), but not other pentaBDE congeners, demonstrated inverse associations with BMI at age 7 years (BMI z-score βadjusted = –1.15; 95% CI: –1.53, –0.77), but there was no interaction by sex.ConclusionsWe estimated sex-specific associations with maternal PBDE levels during pregnancy and BMI at 7 years of age, finding positive associations in boys and negative associations in girls. Children’s serum BDE-153 concentrations were inversely associated with BMI at 7 years with no difference by sex. Future studies should examine the longitudinal trends in obesity with PBDE exposure and changes in hormonal environment as children transition through puberty, as well as evaluate the potential for reverse causality.CitationErkin-Cakmak A, Harley KG, Chevrier J, Bradman A, Kogut K, Huen K, Eskenazi B. 2015. In utero and childhood polybrominated diphenyl ether exposures and body mass at age 7 years: the CHAMACOS Study. Environ Health Perspect 123:636–642; http://dx.doi.org/10.1289/ehp.1408417