1. 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.
- Author
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Keleher MR, Erickson K, Smith HA, Kechris KJ, Yang IV, Dabelea D, Friedman JE, Boyle KE, and Jansson T
- Subjects
- 11-beta-Hydroxysteroid Dehydrogenase Type 2 genetics, Body Mass Index, Child, Child, Preschool, Female, Humans, In Vitro Techniques, Infant, Mitogen-Activated Protein Kinase 9 genetics, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha genetics, Phosphorylation, Pregnancy, p38 Mitogen-Activated Protein Kinases genetics, 11-beta-Hydroxysteroid Dehydrogenase Type 2 metabolism, Insulin metabolism, Insulin-Like Growth Factor I metabolism, Mitogen-Activated Protein Kinase 9 metabolism, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha metabolism, Placenta metabolism, p38 Mitogen-Activated Protein Kinases metabolism
- 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. GSK3β 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., (© 2021 by the American Diabetes Association.)
- Published
- 2021
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