Related Experiment Video
Updated: Jul 5, 2025
Instrumentation of Near-term Fetal Sheep for Multivariate Chronic Non-anesthetized Recordings
Published on: October 25, 2015
Gestational Caloric Restriction Alters Adipose Tissue Methylome and Offspring's Metabolic Profile in a Swine Model
Berta Mas-Parés1, Sílvia Xargay-Torrent1, Gemma Carreras-Badosa1
1Obesity and Cardiovascular Risk in Pediatrics, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain.
Insights
Gestational caloric restriction negatively impacts offspring metabolism and adipose tissue epigenetics. Early metformin intervention shows potential to improve adipocyte morphology and regulate DNA methylation, mitigating adverse effects.
Area of Science:
- Perinatal programming
- Epigenetics
- Metabolic health
Background:
- Fetal nutrient restriction causes adverse offspring adaptations.
- Gestational caloric restriction (GCR) impacts offspring development.
- Epigenetic modifications in adipose tissue are linked to metabolic disease.
Purpose of the Study:
- Investigate GCR and postnatal metformin effects on swine offspring adipose tissue epigenetics.
- Assess associations between epigenetic changes and morphometric/metabolic variables.
- Determine metformin's potential to counteract GCR-induced alterations.
Main Methods:
- Swine model with GCR (30% food restriction) vs. standard diet.
- Postnatal treatment with metformin or vehicle during lactation.
- Analysis of DNA methylation and gene expression in retroperitoneal adipose tissue.
- Assessment of morphometric and metabolic parameters.
Main Results:
- GCR impaired offspring metabolic profiles and increased adipose inflammation.
- GCR altered methylation of metabolism-related genes.
- Metformin improved adipocyte morphology and regulated methylation in key signaling pathways (atherosclerosis, insulin, fatty acids).
- Specific gene methylation (FASN, SLC5A10, COL5A1, PRKCZ) correlated with metabolic profiles in GCR offspring.
Conclusions:
- GCR in pregnancy leads to epigenetic and inflammatory changes in offspring adipose tissue, increasing metabolic abnormality risk.
- Early metformin administration may modulate adipocyte size and DNA methylation, offering a potential therapeutic strategy.
Abstract:
Limited nutrient supply to the fetus results in physiologic and metabolic adaptations that have unfavorable consequences in the offspring. In a swine animal model, we aimed to study the effects of gestational caloric restriction and early postnatal metformin administration on offspring's adipose tissue epigenetics and their association with morphometric and metabolic variables. Sows were either underfed (30% restriction of total food) or kept under standard diet during gestation, and piglets were randomly assigned at birth to receive metformin (n = 16 per group) or vehicle treatment (n = 16 per group) throughout lactation. DNA methylation and gene expression were assessed in the retroperitoneal adipose tissue of piglets at weaning. Results showed that gestational caloric restriction had a negative effect on the metabolic profile of the piglets, increased the expression of inflammatory markers in the adipose tissue, and changed the methylation of several genes related to metabolism. Metformin treatment resulted in positive changes in the adipocyte morphology and regulated the methylation of several genes related to atherosclerosis, insulin, and fatty acids signaling pathways. The methylation and gene expression of the differentially methylated FASN, SLC5A10, COL5A1, and PRKCZ genes in adipose tissue associated with the metabolic profile in the piglets born to underfed sows. In conclusion, our swine model showed that caloric restriction during pregnancy was associated with impaired inflammatory and DNA methylation markers in the offspring's adipose tissue that could predispose the offspring to later metabolic abnormalities. Early metformin administration could modulate the size of adipocytes and the DNA methylation changes.
