TY - JOUR
T1 - Low serum v-3 and v-6 polyunsaturated fatty acids and other metabolites are associated with poor linear growth in young children from rural Malawi
AU - Semba, Richard D.
AU - Trehan, Indi
AU - Li, Ximin
AU - Salem, Norman
AU - Moaddel, Ruin
AU - Ordiz, M. Isabel
AU - Maleta, Kenneth M.
AU - Kraemer, Klaus
AU - Manary, Mark J.
N1 - Funding Information:
Supported by the NIH (R01 AG27012), Intramural Branch of the National Institute on Aging, Children’s Discovery Institute of Washington University, St. Louis Children’s Hospital, and the Hickey Family Foundation. Supplemental Tables 1 and 2 and Supplemental Figure 1 are available from the “Online Supporting Material” link in the online posting of the article and from the same link in the online table of contents at http://ajcn. nutrition.org. Address correspondence to RDS (e-mail: rdsemba@jhmi.edu). Abbreviations used: ARA, arachidonic acid; HAZ, height-for-age z score; RSD, relative SD; UPLC-MS/MS, ultra-HPLC–tandem mass spectrometry. Received July 11, 2017. Accepted for publication October 3, 2017. First published online October 25, 2017; doi: https://doi.org/10.3945/ajcn. 117.164384.
Publisher Copyright:
© 2017 American Society for Nutrition.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Background: Stunting affects w25% of children,5 y of age and is associated with impaired cognitive and motor development and increased morbidity and mortality. The pathogenesis of stunting is poorly understood. Objective: The purpose of this study was to identify altered metabolic pathways associated with child stunting. Design: We measured 677 serum metabolites using liquid chromatography–tandem mass spectrometry in a cross-sectional study of 400 Malawian children aged 12–59 mo, of whom 62% were stunted. Results: A low height-for-age z score (HAZ) was associated with lower serum concentrations of 1) v-3 (n–3) and v-6 (n–6) polyunsaturated fatty acids (PUFAs), 2) sulfated neurosteroids, which play a role in brain development, 3) carnitine, a conditionally essential nutrient with an important role in the carnitine shuttle for the metabolism of fatty acids and energy production, and 4) g-glutamyl amino acids, which represent an altered g-glutamyl cycle of glutathione metabolism. A low HAZ was associated with significantly higher serum concentrations of 5 biomarkers related to cigarette smoke exposure. Conclusions: This metabolomics study shows a cross-sectional association between stunting and low serum v-3 and v-6 long-chain PUFAs, which are essential for growth and development; low sulfated neurosteroids, which play a role in brain development; low carnitine, which is essential for b-oxidation of fatty acids; alterations in glutathione metabolism; and increased serum metabolites that are associated with secondhand tobacco smoke exposure. This trial was registered at www.controlled-trials.com as ISRCTN14597012.
AB - Background: Stunting affects w25% of children,5 y of age and is associated with impaired cognitive and motor development and increased morbidity and mortality. The pathogenesis of stunting is poorly understood. Objective: The purpose of this study was to identify altered metabolic pathways associated with child stunting. Design: We measured 677 serum metabolites using liquid chromatography–tandem mass spectrometry in a cross-sectional study of 400 Malawian children aged 12–59 mo, of whom 62% were stunted. Results: A low height-for-age z score (HAZ) was associated with lower serum concentrations of 1) v-3 (n–3) and v-6 (n–6) polyunsaturated fatty acids (PUFAs), 2) sulfated neurosteroids, which play a role in brain development, 3) carnitine, a conditionally essential nutrient with an important role in the carnitine shuttle for the metabolism of fatty acids and energy production, and 4) g-glutamyl amino acids, which represent an altered g-glutamyl cycle of glutathione metabolism. A low HAZ was associated with significantly higher serum concentrations of 5 biomarkers related to cigarette smoke exposure. Conclusions: This metabolomics study shows a cross-sectional association between stunting and low serum v-3 and v-6 long-chain PUFAs, which are essential for growth and development; low sulfated neurosteroids, which play a role in brain development; low carnitine, which is essential for b-oxidation of fatty acids; alterations in glutathione metabolism; and increased serum metabolites that are associated with secondhand tobacco smoke exposure. This trial was registered at www.controlled-trials.com as ISRCTN14597012.
KW - Arachidonic acid
KW - Carnitine
KW - Dehydroepiandrosterone
KW - Docosahexaenoic acid
KW - Malnutrition
KW - Pregnenolone sulfate
KW - Stunting
UR - http://www.scopus.com/inward/record.url?scp=85038130250&partnerID=8YFLogxK
U2 - 10.3945/ajcn.117.164384
DO - 10.3945/ajcn.117.164384
M3 - Article
C2 - 29070563
AN - SCOPUS:85038130250
SN - 0002-9165
VL - 106
SP - 1490
EP - 1499
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
IS - 6
ER -