Prenatal programming of energy balance and metabolism

​Metformin is the first-in-line medication for type 2 diabetes. Metformin alleviates hyperglycemia by lowering hepatic glucose production and improving insulin sensitivity. Metformin is currently used also for gestational diabetes and for polycystic ovary syndrome during pregnancy. Metformin passes the placenta and the fetus is exposed to the drug directly.

It is known that undernutrition as well as obesity, diabetes and stress during pregnancy can predis-pose the offspring to metabolic disorders in later life, i.e. induce metabolic programming. Although metformin treatment during pregnancy aims to improve maternal metabolism and prevent adverse programming of the fetus, metformin-induced metabolic programming has not been evaluated ex-tensively. The long-term data on the effects of the exposure in humans is still scarce.

Our research group investigates the metabolic effects of prenatal metformin exposure in different pre- and postnatal conditions using mouse models.The critical parameters of the studies are body weight development, body composition, glucose homeostasis and serum lipid values. Furthermore, the underlying mechanisms contributing to prenatal programming are investigated by gene expression microarrays and gut microbiota analyses. We have shown that the offspring exposed to metformin have an altered metabolic phenotype and respond differently to metabolic challenges (i.e. high fat diet) at adulthood depending on the metabolic status during pregnancy. We have also revealed met-formin-induced changes in the gene expression of the neonatal offspring linking the early transcrip-tome to the later phenotype.

List of Personnel

M.Sc. Henriikka Salomäki-Myftari (PhD student of DRDP)
Professor Ullamari Pesonen, PhD

Selected Publications

H. Salomäki, M. Heinäniemi, L. Vähätalo, L. Ailanen, K. Eerola, S. Ruohonen, U. Pesonen and M. Koulu. 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. DOI:10.1371/journal.pone.0115778, 2014.

H. Salomäki, L.H. Vähätalo, K. Laurila,  N.T. Jäppinen,  A-M. Penttinen, L. Ailanen, J. Ily-asizadeh, U. Pesonen and M. Koulu. Prenatal metformin exposure in mice programs the metabolic phenotype of the offspring during high fat diet at adulthood. Plos One 8 (2): e56594. doi:10.1371/journal.pone0056594, 2013.

S-M. Aatsinki, M. Buler, H. Salomäki, M. Koulu, P. Pavek and J. Hakkola. Metformin in-duces PGC-1α expression and selectively affects hepatic PGC-1α functions. Br J Pharmacol 171; 2351-2363, 2014.

H. Salomäki-Myftari1, L.H. Vähätalo, L. Ailanen, S. Pietilä, A.Laiho, A. Hänninen, E. Munukka, E. Savontaus, U. Pesonen and M. Koulu. Female and male mice overexpressing neuropeptide Y show divergent metabolic responses to prenatal metformin exposure. Manuscript  2015.

S.T.  Ruohonen, U. Pesonen, N. Moritz, K. Kaipio, M. Röyttä, M. Koulu and E. Savontaus. Transgenic mouse overexpressing neuropeptide Y in noradrenergic neurons: a novel model of increased adiposity and impaired glucose tolerance. Diabetes 57; 1517-25, 2008.