Placental Insulin/IGF-1 Signaling, PGC-1α, and Inflammatory Pathways Are Associated With Metabolic Outcomes at 4-6 Years of Age: The ECHO Healthy Start Cohort.
Diabetes
; 70(3): 745-751, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-33414248
ABSTRACT
An adverse intrauterine environment is associated with the future risk of obesity and type 2 diabetes. Changes in placental function may underpin the intrauterine origins of adult disease, but longitudinal studies linking placental function with childhood outcomes are rare. Here, we determined the abundance and phosphorylation of protein intermediates involved in insulin signaling, inflammation, cortisol metabolism, protein glycosylation, and mitochondrial biogenesis in placental villus samples from healthy mothers from the Healthy Start cohort. Using MANOVA, we tested the association between placental proteins and offspring adiposity (fat mass percentage) at birth (n = 109) and infancy (4-6 months, n = 104), and adiposity, skinfold thickness, triglycerides, and insulin in children (4-6 years, n = 66). Placental IGF-1 receptor protein was positively associated with serum triglycerides in children. GSK3ß phosphorylation at serine 9, a readout of insulin and growth factor signaling, and the ratio of phosphorylated to total JNK2 were both positively associated with midthigh skinfold thickness in children. Moreover, peroxisome proliferator-activated receptor γ coactivator (PGC)-1α abundance was positively associated with insulin in children. In conclusion, placental insulin/IGF-1 signaling, PGC-1α, and inflammation pathways were positively associated with metabolic outcomes in 4- to 6-year-old children, identifying a novel link between placental function and long-term metabolic outcomes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Placenta
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Fator de Crescimento Insulin-Like I
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11-beta-Hidroxiesteroide Desidrogenase Tipo 2
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Proteína Quinase 9 Ativada por Mitógeno
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Proteínas Quinases p38 Ativadas por Mitógeno
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Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo
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Insulina
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Child
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Child, preschool
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Female
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Humans
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Infant
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Pregnancy
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article