title: Prenatal metformin exposure in a maternal high fat diet mouse model alters the transcriptome and modifies the metabolic responses of the offspring.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, Institute of Biomedicine, University of Turku, FI-20014 Turku, Finland; Drug Research Doctoral Programme (DRDP), University of Turku, Turku, Finland.
authors.forename: Henriikka
authors.initials: H
authors.lastname: Salomäki
authors.affiliation: School of Medicine, Institute of Biomedicine, University of Eastern Finland, FI-70211 Kuopio, Finland.
authors.forename: Merja
authors.initials: M
authors.lastname: Heinäniemi
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, Institute of Biomedicine, University of Turku, FI-20014 Turku, Finland; Drug Research Doctoral Programme (DRDP), University of Turku, Turku, Finland; Turku Center for Disease Modeling (TCDM), University of Turku, FI-20014 Turku, Finland.
authors.forename: Laura H
authors.initials: LH
authors.lastname: Vähätalo
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, Institute of Biomedicine, University of Turku, FI-20014 Turku, Finland; Drug Research Doctoral Programme (DRDP), University of Turku, Turku, Finland; Turku Center for Disease Modeling (TCDM), University of Turku, FI-20014 Turku, Finland.
authors.forename: Liisa
authors.initials: L
authors.lastname: Ailanen
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, Institute of Biomedicine, University of Turku, FI-20014 Turku, Finland; Drug Research Doctoral Programme (DRDP), University of Turku, Turku, Finland; Turku Center for Disease Modeling (TCDM), University of Turku, FI-20014 Turku, Finland.
authors.forename: Kim
authors.initials: K
authors.lastname: Eerola
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, Institute of Biomedicine, University of Turku, FI-20014 Turku, Finland; Turku Center for Disease Modeling (TCDM), University of Turku, FI-20014 Turku, Finland.
authors.forename: Suvi T
authors.initials: ST
authors.lastname: Ruohonen
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, Institute of Biomedicine, University of Turku, FI-20014 Turku, Finland.
authors.forename: Ullamari
authors.initials: U
authors.lastname: Pesonen
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, Institute of Biomedicine, University of Turku, FI-20014 Turku, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Koulu
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D054392:Adipokines / Q000097:blood; D052436:Adipose Tissue, White / Q000166:cytology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D005333:Fetus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005951:Glucose Tolerance Test; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics* / Q000378:metabolism*; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D054392:Adipokines; D001786:Blood Glucose; D008055:Lipids; D008687:Metformin