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

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Maxim D SeferovicKjersti M Aagaard

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...Continue Reading

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Citations

Aug 15, 2018·American Journal of Physiology. Endocrinology and Metabolism·Maxim D SeferovicMaureen Gannon
Feb 18, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sarah E McKeeTeresa M Reyes
Aug 12, 2019·BMJ Open·Debora Farias Batista LeiteJose Guilherme Cecatti
Jan 8, 2021·Journal of the American Society of Nephrology : JASN·Ellen E GillisJennifer C Sullivan
Feb 18, 2016·American Journal of Obstetrics and Gynecology·Pablo Gonzalez-RodriguezKjersti M Aagaard

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