Prenatal metformin exposure in a maternal high fat diet mouse model alters the transcriptome and modifies the metabolic responses of the offspring.
PLoS One
; 9(12): e115778, 2014.
Article
de En
| MEDLINE
| ID: mdl-25541979
ABSTRACT
AIMS:
Despite the wide use of metformin in metabolically challenged pregnancies, the long-term effects on the metabolism of the offspring are not known. We studied the long-term effects of prenatal metformin exposure during metabolically challenged pregnancy in mice. MATERIALS ANDMETHODS:
Female mice were on a high fat diet (HFD) prior to and during the gestation. Metformin was administered during gestation from E0.5 to E17.5. Male and female offspring were weaned to a regular diet (RD) and subjected to HFD at adulthood (10-11 weeks). Body weight and several metabolic parameters (e.g. body composition and glucose tolerance) were measured during the study. Microarray and subsequent pathway analyses on the liver and subcutaneous adipose tissue of the male offspring were performed at postnatal day 4 in a separate experiment.RESULTS:
Prenatal metformin exposure changed the offspring's response to HFD. Metformin exposed offspring gained less body weight and adipose tissue during the HFD phase. Additionally, prenatal metformin exposure prevented HFD-induced impairment in glucose tolerance. Microarray and annotation analyses revealed metformin-induced changes in several metabolic pathways from which electron transport chain (ETC) was prominently affected both in the neonatal liver and adipose tissue.CONCLUSION:
This study shows the beneficial effects of prenatal metformin exposure on the offspring's glucose tolerance and fat mass accumulation during HFD. The transcriptome data obtained at neonatal age indicates major effects on the genes involved in mitochondrial ATP production and adipocyte differentiation suggesting the mechanistic routes to improved metabolic phenotype at adulthood.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Effets différés de l'exposition prénatale à des facteurs de risque
/
Transcriptome
/
Alimentation riche en graisse
/
Metformine
Limites:
Animals
/
Pregnancy
Langue:
En
Journal:
PLoS One
Sujet du journal:
CIENCIA
/
MEDICINA
Année:
2014
Type de document:
Article
Pays d'affiliation:
Finlande