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Heritable IUGR and adult metabolic syndrome are reversible and associated with alterations in the metabolome following dietary supplementation of 1-carbon intermediates.

Authors :
Seferovic, Maxim D.
Goodspeed, Danielle M.
Chu, Derrick M.
Krannich, Laura A.
Gonzalez-Rodriguez, Pablo J.
Cox, James E.
Aagaard, Kjersti M.
Source :
FASEB Journal; Jun2015, Vol. 29 Issue 6, p2640-2652, 13p
Publication Year :
2015

Abstract

Metabolic syndrome (MetS), following intrauterine growth restriction (IUGR), is epigenetically heritable. Recently, we abrogated the F2 adult phenotype with essential nutrient supplementation (ENS) of intermediates along the 1-carbon pathway. With the use of the same grandparental uterine artery ligation model, we profiled the F2 serum metabolome at weaning [postnatal day (d)21; n = 76] and adulthood (d160; n = 12) to test if MetS is preceded by alterations in the metabolome. Indicative of developmentally programmed MetS, adult F2, formerly IUGR rats, were obese (621 vs. 461 g; P < 0.0001), dyslipidemic (133 vs. 67 mg/dl; P < 0.001), and glucose intolerant (26 vs. 15 mg/kg/min; P < 0.01). Unbiased gas chromatography-mass spectrometry (GC-MS) profiling revealed 34 peaks corresponding to 12 nonredundant metabolites and 9 unknowns to be changing at weaning [false discovery rate (FDR) < 0.05]. Markers of later-in-life MetS included citric acid, glucosamine, myoinositol, and proline (P < 0.03). Hierarchical clustering revealed grouping by IUGR lineage and supplementation at d21 and d160. Weanlings grouped distinctly for ENS and IUGR by partial least-squares discriminate analysis (PLS-DA; P < 0.01), whereas paternal and maternal IUGR (IUGR<superscript>pat</superscript>/IUGR<superscript>mat</superscript>, respectively) control-fed rats, destined for MetS, had a distinct metabolome at weaning (randomForest analysis; class error < 0.1) and adulthood (PLS-DA; P < 0.05). In sum, we have found that alterations in the metabolome accompany heritable IUGR, precede adult-onset MetS, and are partially amenable to dietary intervention. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
08926638
Volume :
29
Issue :
6
Database :
Complementary Index
Journal :
FASEB Journal
Publication Type :
Academic Journal
Accession number :
103017243
Full Text :
https://doi.org/10.1096/fj.14-266387