Gestational Caloric Restriction Alters Adipose Tissue Methylome and Offspring's Metabolic Profile in a Swine Model
Por:
Mas-Parés B, Xargay-Torrent S, Carreras-Badosa G, Gómez-Vilarrubla A, Niubó-Pallàs M, Tibau J, Reixach J, Prats-Puig A, de Zegher F, Ibañez-Toda L, Bassols J and López-Bermejo A
Publicada:
1 ene 2024
Ahead of Print:
17 ene 2024
Resumen:
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.
Filiaciones:
Mas-Parés B:
Obesity and Cardiovascular Risk in Pediatrics, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
Xargay-Torrent S:
Obesity and Cardiovascular Risk in Pediatrics, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
Carreras-Badosa G:
Obesity and Cardiovascular Risk in Pediatrics, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
Gómez-Vilarrubla A:
Materno-Fetal Metabolic Research, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
Niubó-Pallàs M:
Materno-Fetal Metabolic Research, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
Tibau J:
Benestar Animal, Institut de Recerca i Tecnología Agroalimentàries (IRTA), 17121 Monells, Spain
Reixach J:
Selecció Batallé, 17421 Riudarenes, Spain
Prats-Puig A:
Department of Physical Therapy, EUSES, University of Girona, 17190 Salt, Spain
de Zegher F:
Department of Development and Regeneration, University of Leuven, 3000 Leuven, Belgium
Ibañez-Toda L:
Endocrinology, Fundació Sant Joan de Déu, University of Barcelona, 08950 Esplugues de Llobregat, Spain
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, 28029 Madrid, Spain
Bassols J:
Materno-Fetal Metabolic Research, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
López-Bermejo A:
Obesity and Cardiovascular Risk in Pediatrics, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
Pediatrics, Hospital Dr. Josep Trueta, 17007 Girona, Spain
Department of Medical Sciences, University of Girona, 17820 Girona, Spain
Green Submitted, Green Accepted, gold
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