Short-term isocaloric fructose restriction lowers apoC-III levels and yields less atherogenic lipoprotein profiles in children with obesity and metabolic syndrome

短期等热量果糖限制可降低肥胖和代谢综合征儿童的 apoC-III 水平,并减少动脉粥样硬化脂蛋白谱

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作者:Alejandro Gugliucci, Robert H Lustig, Russell Caccavello, Ayca Erkin-Cakmak, Susan M Noworolski, Viva W Tai, Michael J Wen, Kathleen Mulligan, Jean-Marc Schwarz

Aims

Dietary fructose may play a role in the pathogenesis of metabolic syndrome (MetS). In a recently published study of obese children with MetS, we showed that isocaloric fructose restriction reduced fasting triglyceride (TG) and LDL-cholesterol (LDL-C). In these ancillary analyses, we tested the hypothesis that these effects were also accompanied by improved quantitative and qualitative changes in LDL and HDL subclasses and their apolipoproteins; as well as change in VLDL, particularly apoC-III.

Background and aims

Dietary fructose may play a role in the pathogenesis of metabolic syndrome (MetS). In a recently published study of obese children with MetS, we showed that isocaloric fructose restriction reduced fasting triglyceride (TG) and LDL-cholesterol (LDL-C). In these ancillary analyses, we tested the hypothesis that these effects were also accompanied by improved quantitative and qualitative changes in LDL and HDL subclasses and their apolipoproteins; as well as change in VLDL, particularly apoC-III.

Conclusions

Isocaloric fructose restriction for 9 days improved lipoprotein markers of CVD risk in children with obesity and MetS. The most dramatic reduction was seen for apoC-III, which has been associated with atherogenic hypertriglyceridemia.

Methods

Obese children with MetS (n = 37) consumed a diet that matched self-reported macronutrient composition for nine days, with the exception that dietary fructose was reduced from 11.7 ± 4.0% to 3.8 ± 0.5% of daily calories and substituted with glucose (in starch). Participants underwent fasting biochemical analyses on Days 0 and 10. HDL and LDL subclasses were analyzed using the Lipoprint HDL and LDL subfraction analysis systems from Quantimetrix.

Results

Significant reductions in apoB (78 ± 24 vs. 66 ± 24 mg/dl) apoC-III (8.7 ± 3.5 vs. 6.5 ± 2.6 mg/dl) and apoE (4.6 ± 2.3 vs. 3.6 ± 1.1 mg/dl), all p < 0.001) were observed. LDL size increased by 0.87 Å (p = 0.008). Small dense LDL was present in 25% of our cohort and decreased by 68% (p = 0.04). Small HDL decreased by 2.7% (p < 0.001) and large HDL increased by 2.4% (p = 0.04). The TG/HDL-C ratio decreased from 3.1 ± 2.5 to 2.4 ± 1.4 (p = 0.02). These changes in fasting lipid profiles correlated with changes in insulin sensitivity. Conclusions: Isocaloric fructose restriction for 9 days improved lipoprotein markers of CVD risk in children with obesity and MetS. The most dramatic reduction was seen for apoC-III, which has been associated with atherogenic hypertriglyceridemia.

Trial registration

ClinicalTrials.gov NCT01200043.

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