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Placental insulin-mTOR and stress-inflammatory signaling patterns are associated with childhood adiposity
Ellen C Francis1, Kristen E Boyle2,3, Lauren E Gyllenhammer4
1Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, New Jersey, United States. Ellen.Francis@Rutgers.edu.
Insights
Placental signaling patterns influence childhood adiposity. One pattern linked to insulin and energy sensing was associated with lower body fat, while a stress-inflammatory pattern correlated with higher body fat and metabolic changes.
Area of Science:
- Reproductive biology and developmental origins of health and disease.
- Endocrinology and metabolic health research.
- Placental biology and fetal programming.
Background:
- Placental signaling pathways are crucial for nutrient transport and fetal growth, impacting offspring metabolic health.
- Previous research often examined single placental markers, limiting understanding of coordinated pathway activity.
- Investigating combined placental signaling patterns offers deeper insights into offspring health outcomes.
Purpose of the Study:
- To identify latent patterns across placental nutrient signaling pathways.
- To assess associations between these placental patterns and early childhood adiposity (% fat mass).
- To explore links between adiposity-associated patterns and metabolic biomarkers in early childhood.
Main Methods:
- Quantified 33 placental signaling proteins and their phosphorylation ratios in 108 mother-child pairs.
- Utilized unsupervised methods to identify latent signaling patterns in placental villus tissue.
- Applied LASSO and multivariable regression to analyze associations with childhood % fat mass and metabolic markers.
Main Results:
- Identified two distinct placental signaling patterns associated with childhood % fat mass.
- An insulin-mTOR-energy sensing pattern correlated with lower % fat mass and higher adiponectin.
- A stress-inflammatory MAPK pattern correlated with higher % fat mass, leptin, and triglycerides.
Conclusions:
- Specific placental signaling patterns are linked to childhood adiposity and metabolic profiles.
- These findings highlight the importance of examining coordinated placental pathway activity.
- Understanding these placental patterns may illuminate the early origins of adiposity and metabolic health.
Background:
Placental signaling pathways regulate nutrient transport and fetal growth, with potential long-term consequences for offspring metabolic health. Most prior human studies have focused on individual placental markers, limiting insight into the role of coordinated activity across multiple pathways in relation to offspring outcomes. Our objective was to identify patterns across placental nutrient signaling pathways and assess whether the latent placental signaling patterns were associated with early childhood adiposity, and secondarily, explore associations of adiposity-associated patterns with metabolic biomarkers.
Methods:
Among 108 mother-child pairs from the Healthy Start cohort, we quantified 33 placental signaling proteins and their phosphorylated-to-total protein ratios involved in nutrient sensing, insulin/growth factor signaling, stress/inflammation, and mitochondrial biogenesis using Simple Western assays of term placental villus tissue. We applied unsupervised methods to identify latent patterns and LASSO regression was used to select patterns associated with %fat mass at age 4. Multivariable linear regression was used to estimate associations adjusting for offspring age, sex, and maternal pre-pregnancy BMI. These same models were used in exploratory analysis of fasting levels of adiponectin, leptin, insulin, glucose, and lipids at age 4.
Results:
We identified two placental signaling patterns associated with %fat mass. The insulin-mTOR-energy sensing pattern was associated with lower childhood %fat mass (β = -2.46, 95% CI - 4.84, - 0.09) and adiponectin, and the stress-inflammatory MAPK pattern was associated with higher %fat mass (β = 1.28, 95% CI 0.05, 2.51), leptin, and triglycerides; however, the FDR p-values ranged from 0.06 to 0.13.
Conclusion:
Two placental signaling patterns were associated with childhood %fat mass and metabolic markers. These findings indicate that capturing placental activity across several signaling pathways may yield insights into early origins of adiposity and metabolic health.
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