Prenatal metformin exposure in mice programs the metabolic phenotype of the offspring during a high fat diet at adulthood

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dc.contributor Aalto-yliopisto fi
dc.contributor Aalto University en Salomäki, Henriikka Vähätalo, Laura H. Laurila, Kirsti Jäppinen, Norma T. Penttinen, Anna-Maija Ailanen, Liisa Ilyasizadeh, Juan Pesonen, Ullamari Koulu, Markku 2017-05-11T09:15:52Z 2017-05-11T09:15:52Z 2013
dc.identifier.citation Salomäki , H , Vähätalo , L H , Laurila , K , Jäppinen , N T , Penttinen , A-M , Ailanen , L , Ilyasizadeh , J , Pesonen , U & Koulu , M 2013 , ' Prenatal metformin exposure in mice programs the metabolic phenotype of the offspring during a high fat diet at adulthood ' PLOS ONE , vol 8 , no. 2 , e56594 , pp. 1-12 . DOI: 10.1371/journal.pone.0056594 en
dc.identifier.issn 1932-6203
dc.identifier.other PURE UUID: f64e6396-5c3b-4db2-8a6f-7bc5debe4fc5
dc.identifier.other PURE ITEMURL:
dc.identifier.other PURE FILEURL:
dc.description.abstract Aims The antidiabetic drug metformin is currently used prior and during pregnancy for polycystic ovary syndrome, as well as during gestational diabetes mellitus. We investigated the effects of prenatal metformin exposure on the metabolic phenotype of the offspring during adulthood in mice. Methods Metformin (300 mg/kg) or vehicle was administered orally to dams on regular diet from the embryonic day E0.5 to E17.5. Gene expression profiles in liver and brain were analysed from 4-day old offspring by microarray. Body weight development and several metabolic parameters of offspring were monitored both during regular diet (RD-phase) and high fat diet (HFD-phase). At the end of the study, two doses of metformin or vehicle were given acutely to mice at the age of 20 weeks, and Insig-1 and GLUT4 mRNA expressions in liver and fat tissue were analysed using qRT-PCR. Results Metformin exposed fetuses were lighter at E18.5. There was no effect of metformin on the maternal body weight development or food intake. Metformin exposed offspring gained more body weight and mesenteric fat during the HFD-phase. The male offspring also had impaired glucose tolerance and elevated fasting glucose during the HFD-phase. Moreover, the expression of GLUT4 mRNA was down-regulated in epididymal fat in male offspring prenatally exposed to metformin. Based on the microarray and subsequent qRT-PCR analyses, the expression of Insig-1 was changed in the liver of neonatal mice exposed to metformin prenatally. Furthermore, metformin up-regulated the expression of Insig-1 later in development. Gene set enrichment analysis based on preliminary microarray data identified several differentially enriched pathways both in control and metformin exposed mice. Conclusions The present study shows that prenatal metformin exposure causes long-term programming effects on the metabolic phenotype during high fat diet in mice. This should be taken into consideration when using metformin as a therapeutic agent during pregnancy. en
dc.format.extent 1-12
dc.format.mimetype application/pdf
dc.language.iso en en
dc.relation.ispartofseries PLOS ONE en
dc.relation.ispartofseries Volume 8, issue 2 en
dc.rights openAccess en
dc.subject.other 512 Business and management en
dc.subject.other 111 Mathematics en
dc.subject.other 112 Statistics and probability en
dc.subject.other 113 Computer and information sciences en
dc.title Prenatal metformin exposure in mice programs the metabolic phenotype of the offspring during a high fat diet at adulthood en
dc.type A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä fi
dc.description.version Peer reviewed en
dc.contributor.department Department of Information and Service Management
dc.subject.keyword 512 Business and management
dc.subject.keyword 111 Mathematics
dc.subject.keyword 112 Statistics and probability
dc.subject.keyword 113 Computer and information sciences
dc.identifier.urn URN:NBN:fi:aalto-201705114355
dc.identifier.doi 10.1371/journal.pone.0056594
dc.type.version publishedVersion

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