A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Prenatal Metformin Exposure in a Maternal High Fat Diet Mouse Model Alters the Transcriptome and Modifies the Metabolic Responses of the Offspring
Tekijät: Salomäki H, Heinäniemi M, Vähätalo LH, Ailanen L, Eerola K, Ruohonen ST, Pesonen U, Koulu M.
Julkaisuvuosi: 2014
Journal: PLoS ONE
Vuosikerta: 9
Numero: 12
Sivujen määrä: 22
ISSN: 1932-6203
DOI: https://doi.org/10.1371/journal.pone.0115778
Tiivistelmä
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 and Methods: 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.
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 and Methods: 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.
Turun yliopiston Tutkimustietojärjestelmän portaali