Lipid-Based Nutrient Supplementation Increases High-Density Lipoprotein (HDL) Cholesterol Efflux Capacity and Is Associated with Changes in the HDL Glycoproteome in Children

Brian V Hong, Chenghao Zhu, Maurice Wong, Romina Sacchi, Christopher H Rhodes, Jea Woo Kang, Charles D Arnold, Seth Adu-Afarwuah, Anna Lartey, Brietta M Oaks, Carlito B Lebrilla, Kathryn G Dewey, Angela M Zivkovic, Brian V Hong, Chenghao Zhu, Maurice Wong, Romina Sacchi, Christopher H Rhodes, Jea Woo Kang, Charles D Arnold, Seth Adu-Afarwuah, Anna Lartey, Brietta M Oaks, Carlito B Lebrilla, Kathryn G Dewey, Angela M Zivkovic

Abstract

Prenatal plus postnatal small-quantity lipid-based nutrient supplements (SQ-LNS) improved child growth at 18 months in the International Lipid-Based Nutrient Supplements DYAD trial in Ghana. In this secondary outcome analysis, we determined whether SQ-LNS versus prenatal iron and folic acid (IFA) supplementation improves the cholesterol efflux capacity (CEC) of high-density lipoprotein (HDL) particles and alters their lipidomic, proteomic, or glycoproteomic composition in a subset of 80 children at 18 months of age. HDL CEC was higher among children in the SQ-LNS versus IFA group (20.9 ± 4.1 vs 19.4 ± 3.3%; one-tailed p = 0.038). There were no differences in HDL lipidomic or proteomic composition between groups. Twelve glycopeptides out of the 163 analyzed were significantly altered by SQ-LNS, but none of the group differences remained significant after correction for multiple testing. Exploratory analysis showed that 6 out of the 33 HDL-associated proteins monitored differed in glycopeptide enrichment between intervention groups, and 6 out of the 163 glycopeptides were correlated with CEC. We conclude that prenatal plus postnatal SQ-LNS may modify HDL protein glycoprofiles and improve the CEC of HDL particles in children, which may have implications for subsequent child health outcomes. This trial was registered at clinicaltrials.gov as NCT00970866.

Conflict of interest statement

The authors declare no competing financial interest.

© 2021 The Authors. Published by American Chemical Society.

Figures

Figure 1
Figure 1
Volcano plots of the intervention effects on HDL lipid species (A) and HDL glycopeptides (B). The log fold changes of all measured variables are displayed on the x-axis and the −log(p-value) on the y-axis. Variables with p-value <0.05 were labeled. p-values were not corrected for multiple testing.
Figure 2
Figure 2
Enrichment analysis of glycopeptides in the IFA and SQ-LNS group. Out of the 33 HDL-associated proteins monitored, 21 contained glycopeptides. Six glycopeptides from a subset of the 21 proteins differed significantly in enrichment between intervention groups. Enrichment is characterized as the total amount of glycopeptides of a particular protein across all glycosylation sites as a measure of the degree of glycosylation of that protein. Number of glycopeptides of APOC3 (apolipoprotein C-III), CLUS (clusterin), PON1 (paraoxonase 1), AACT, FETUA, and A1AT (alpha-1-antitrypsin) that are lower (left panel) or higher (right panel) in children in the SQ-LNS compared to the IFA intervention group. SQ-LNS, small-quantity lipid-based nutrient supplements; IFA, iron and folic acid; HDL, high-density lipoproteins.
Figure 3
Figure 3
A: Dotmap of the SQ-LNS effects on HDL glycopeptides and glycopeptide correlation with CEC. Glycopeptides that were significantly different (p ≤ 0.05) between intervention groups are shown. The darkness of the background indicates the p-value. The dot size represents glycopeptide log fold changes in the abundance analysis. B–G: Scatterplot of all glycopeptides associated with HDL CEC, including glycopeptides A1AT_70_5402 (B), FETUA_156_6513 (C), PON1_324_6503 (D), APOD_98_5402 (E), APOD_65_6503 (F), and A1AT_70_5412 (G). CEC, cholesterol efflux capacity; HDL, high-density lipoprotein; SQ-LNS, small-quantity lipid-based nutrient supplements; A1AT, alpha-1-antitrypsin; FETUA, alpha-2-HS-glycoprotein; PON1, serum paraoxonase/arylesterase 1; APOD, apolipoprotein D.

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