期刊
DIABETES
卷 70, 期 3, 页码 745-751出版社
AMER DIABETES ASSOC
DOI: 10.2337/db20-0902
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资金
- Colorado Clinical and Translational Sciences Institute [UG3OD023248-03]
- American Heart Association [14PRE18230008]
- parent Healthy Start Study
- National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK076648]
- Colorado Clinical and Translational Sciences Institute via National Institutes of Health, National Center for Advancing Translational Sciences [UL1 TR001082]
Placental insulin/IGF-1 signaling, PGC-1 alpha, 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.
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. GSK3 beta 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 gamma coactivator (PGC)-1 alpha abundance was positively associated with insulin in children. In conclusion, placental insulin/IGF-1 signaling, PGC-1 alpha, 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.
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