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

Tutkimustuotos: Lehtiartikkelivertaisarvioitu

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Prenatal metformin exposure in mice programs the metabolic phenotype of the offspring during a high fat diet at adulthood. / Salomäki, Henriikka; Vähätalo, Laura H.; Laurila, Kirsti; Jäppinen, Norma T.; Penttinen, Anna-Maija; Ailanen, Liisa; Ilyasizadeh, Juan; Pesonen, Ullamari; Koulu, Markku.

julkaisussa: PloS one, Vuosikerta 8, Nro 2, e56594, 2013, s. 1-12.

Tutkimustuotos: Lehtiartikkelivertaisarvioitu

Harvard

Salomäki, H, Vähätalo, LH, Laurila, K, Jäppinen, NT, 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, Vuosikerta. 8, Nro 2, e56594, Sivut 1-12. https://doi.org/10.1371/journal.pone.0056594

APA

Salomäki, H., Vähätalo, L. H., Laurila, K., Jäppinen, N. T., Penttinen, A-M., Ailanen, L., ... Koulu, M. (2013). Prenatal metformin exposure in mice programs the metabolic phenotype of the offspring during a high fat diet at adulthood. PloS one, 8(2), 1-12. [e56594]. https://doi.org/10.1371/journal.pone.0056594

Vancouver

Author

Salomäki, Henriikka ; Vähätalo, Laura H. ; Laurila, Kirsti ; Jäppinen, Norma T. ; Penttinen, Anna-Maija ; Ailanen, Liisa ; Ilyasizadeh, Juan ; Pesonen, Ullamari ; Koulu, Markku. / Prenatal metformin exposure in mice programs the metabolic phenotype of the offspring during a high fat diet at adulthood. Julkaisussa: PloS one. 2013 ; Vuosikerta 8, Nro 2. Sivut 1-12.

Bibtex - Lataa

@article{f64e63965c3b4db28a6f7bc5debe4fc5,
title = "Prenatal metformin exposure in mice programs the metabolic phenotype of the offspring during a high fat diet at adulthood",
abstract = "AimsThe 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.MethodsMetformin (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.ResultsMetformin 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.ConclusionsThe 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.",
author = "Henriikka Salom{\"a}ki and V{\"a}h{\"a}talo, {Laura H.} and Kirsti Laurila and J{\"a}ppinen, {Norma T.} and Anna-Maija Penttinen and Liisa Ailanen and Juan Ilyasizadeh and Ullamari Pesonen and Markku Koulu",
year = "2013",
doi = "10.1371/journal.pone.0056594",
language = "English",
volume = "8",
pages = "1--12",
journal = "PloS one",
issn = "1932-6203",
number = "2",

}

RIS - Lataa

TY - JOUR

T1 - Prenatal metformin exposure in mice programs the metabolic phenotype of the offspring during a high fat diet at adulthood

AU - Salomäki, Henriikka

AU - Vähätalo, Laura H.

AU - Laurila, Kirsti

AU - Jäppinen, Norma T.

AU - Penttinen, Anna-Maija

AU - Ailanen, Liisa

AU - Ilyasizadeh, Juan

AU - Pesonen, Ullamari

AU - Koulu, Markku

PY - 2013

Y1 - 2013

N2 - AimsThe 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.MethodsMetformin (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.ResultsMetformin 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.ConclusionsThe 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.

AB - AimsThe 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.MethodsMetformin (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.ResultsMetformin 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.ConclusionsThe 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.

U2 - 10.1371/journal.pone.0056594

DO - 10.1371/journal.pone.0056594

M3 - Article

VL - 8

SP - 1

EP - 12

JO - PloS one

JF - PloS one

SN - 1932-6203

IS - 2

M1 - e56594

ER -

ID: 831203