Maternal Western diet programs persistent transcriptomic signatures in offspring PBMCs that are largely reversible by...

Area of Science:

• Developmental biology
• Nutritional science
• Genomics

Background:

• Maternal Western diet (WD) during pregnancy and lactation can program long-term metabolic dysfunction in offspring.
• It is unclear if these effects leave a lasting transcriptomic signature into adulthood or if postnatal interventions can reverse them.

Purpose of the Study:

• To identify long-term transcriptomic signatures in adult offspring exposed to maternal WD.
• To evaluate if maternal dietary normalization or leptin supplementation during lactation can reverse these signatures.

Main Methods:

• Used peripheral blood mononuclear cells (PBMCs) from adult offspring of dams fed WD or control diets.
• Assessed transcriptomic changes and the impact of two postnatal interventions: maternal dietary normalization and pup leptin supplementation.
• Employed multivariate analyses (PLS-DA) to identify key gene expression differences.

Main Results:

• Maternal WD altered the expression of 90 genes in offspring PBMCs.
• Both interventions normalized the expression of most altered genes (83% and 76%).
• Transcriptomic profiles shifted towards control levels, with stronger effects in males, indicating dysregulation of immunometabolic pathways.

Conclusions:

• Early-life interventions during lactation can reverse most transcriptomic alterations caused by maternal WD exposure.
• Lactation represents a critical window for postnatal reprogramming.
• PBMC transcriptomic signatures may serve as biomarkers for developmental programming due to adverse maternal diet.