Maternal Metformin Intervention during Obese Glucose-Intolerant Pregnancy Affects Adiposity in Young Adult Mouse Offspring in a Sex-Specific Manner.
Ashmore, Thomas J
International journal of molecular sciences
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Schoonejans, J., Blackmore, H. L., Ashmore, T. J., Aiken, C., Twinn, D., & Ozanne, S. (2021). Maternal Metformin Intervention during Obese Glucose-Intolerant Pregnancy Affects Adiposity in Young Adult Mouse Offspring in a Sex-Specific Manner.. International journal of molecular sciences, 22 (15)https://doi.org/10.3390/ijms22158104
Background: Metformin is commonly used to treat gestational diabetes mellitus. This study investigated the effect of maternal metformin intervention during obese glucose-intolerant pregnancy on gonadal white adipose tissue (WAT) of 8-week-old male and female mouse offspring. Methods: C57BL/6J female mice were provided with control (Con) or obesogenic diet (Ob) to induce pre-conception obesity. Half the obese dams were treated orally with 300mg/kg/d metformin (Ob-Met) during pregnancy. Gonadal WAT depots from 8-week-old male and investigated for adipocyte size, macrophage infiltration and mRNA expression of pro-inflammatory genes using RT-PCR. Results: Gestational metformin attenuated adiposity in obese dams and increased gestation length without correcting offspring in-utero growth restriction and catch-up growth caused by maternal obesity. Despite similar body weight, Ob and Ob-Met offspring of both sexes showed adipocyte hypertrophy in young adulthood. Male Ob-Met offspring had increased WAT depot weight (p<0.05), exaggerated adipocyte hyperplasia (p<0.05 vs Con and Ob offspring), increased macrophage infiltration measured via histology (p<0.05) and mRNA expression of F4/80 (p<0.05). These changes were not observed in female Ob-Met offspring. Conclusions: Maternal metformin intervention during obese pregnancy causes excessive adiposity, adipocyte hyperplasia and WAT inflammation in male offspring, highlighting sex-specific effects of prenatal metformin exposure on offspring WAT.
Animals, Mice, Inbred C57BL, Animals, Newborn, Mice, Diabetes, Gestational, Prenatal Exposure Delayed Effects, Metformin, Sex Factors, Pregnancy, Female, Male, Adiposity, Obesity, Maternal
British Heart Foundation (RG/17/12/33167)
British Heart Foundation (PG/13/46/30329)
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External DOI: https://doi.org/10.3390/ijms22158104
This record's URL: https://www.repository.cam.ac.uk/handle/1810/325422
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