Neuropeptide Y Overexpressing Female and Male Mice Show Divergent Metabolic but Not Gut Microbial Responses to Prenatal Metformin Exposure.
BACKGROUND
Prenatal metformin exposure has been shown to improve the metabolic outcome in the offspring of high fat diet fed dams. However, if this is evident also in a genetic model of obesity and whether gut microbiota has a role, is not known.


METHODS
The metabolic effects of prenatal metformin exposure were investigated in a genetic model of obesity, mice overexpressing neuropeptide Y in the sympathetic nervous system and in brain noradrenergic neurons (OE-NPYDβH). Metformin was given for 18 days to the mated female mice. Body weight, body composition, glucose tolerance and serum parameters of the offspring were investigated on regular diet from weaning and sequentially on western diet (at the age of 5-7 months). Gut microbiota composition was analysed by 16S rRNA sequencing at 10-11 weeks.


RESULTS
In the male offspring, metformin exposure inhibited weight gain. Moreover, weight of white fat depots and serum insulin and lipids tended to be lower at 7 months. In contrast, in the female offspring, metformin exposure impaired glucose tolerance at 3 months, and subsequently increased body weight gain, fat mass and serum cholesterol. In the gut microbiota, a decline in Erysipelotrichaceae and Odoribacter was detected in the metformin exposed offspring. Furthermore, the abundance of Sutterella tended to be decreased and Parabacteroides increased. Gut microbiota composition of the metformin exposed male offspring correlated to their metabolic phenotype.


CONCLUSIONS
Prenatal metformin exposure caused divergent metabolic phenotypes in the female and male offspring. Nevertheless, gut microbiota of metformin exposed offspring was similarly modified in both genders.
Institute of Biomedicine, Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.|Drug Research Doctoral Programme (DRDP), University of Turku, Turku, Finland.
Henriikka
H
Salomäki-Myftari
Institute of Biomedicine, Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.|Drug Research Doctoral Programme (DRDP), University of Turku, Turku, Finland.
Laura H
LH
Vähätalo
Institute of Biomedicine, Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.|Drug Research Doctoral Programme (DRDP), University of Turku, Turku, Finland.
Liisa
L
Ailanen
Bioinformatics Unit, Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
Sami
S
Pietilä
Bioinformatics Unit, Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
Asta
A
Laiho
Institute of Biomedicine, Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
Arno
A
Hänninen
Turku Clinical Sequencing Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland.
Juha-Pekka
JP
Pursiheimo
Institute of Biomedicine, Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
Eveliina
E
Munukka
Institute of Biomedicine, Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
Anniina
A
Rintala
Institute of Biomedicine, Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
Eriika
E
Savontaus
Institute of Biomedicine, Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
Ullamari
U
Pesonen
Institute of Biomedicine, Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
Markku
M
Koulu
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