PP2_Supplementary_Figures.pdf (1.51 MB)
Placental Insulin/IGF-1 Signaling, PGC1α, and Inflammatory Pathways are Associated With Metabolic Outcomes at 4-6 years of Age: The ECHO Healthy Start Cohort
figure
posted on 2021-01-07, 22:14 authored by Madeline Rose Keleher, Kathryn Erickson, Harry A. Smith, Katerina J. Kechris, Ivana V. Yang, Dana Dabelea, Jacob E. Friedman, Kristen E. Boyle, Thomas JanssonAn 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 (percent fat
mass) at birth (n=109) and infancy (4-6mo, n=104), and adiposity, skinfold
thickness, triglycerides, and insulin in children (4-6y, 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, 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 4-6-year-old children, identifying a novel link
between placental function and long-term metabolic outcomes.