Maternal Metformin Intervention during Obese Glucose-Intolerant Pregnancy Affects Adiposity in Young Adult Mouse Offspring in a Sex-Specific Manner.
Published version
Peer-reviewed
Repository URI
Repository DOI
Change log
Authors
Schoonejans, Josca M https://orcid.org/0000-0003-2893-7199
Blackmore, Heather L https://orcid.org/0000-0003-0180-3852
Ashmore, Thomas J
Aiken, Catherine E
Fernandez-Twinn, Denise S https://orcid.org/0000-0003-2610-277X
Abstract
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 the gonadal white adipose tissue (WAT) of 8-week-old male and female mouse offspring.Methods
C57BL/6J female mice were provided with a control (Con) or obesogenic diet (Ob) to induce pre-conception obesity. Half the obese dams were treated orally with 300 mg/kg/d of metformin (Ob-Met) during pregnancy. Gonadal WAT depots from 8-week-old offspring were investigated for adipocyte size, macrophage infiltration and mRNA expression of pro-inflammatory genes using RT-PCR.Results
Gestational metformin attenuated the adiposity in obese dams and increased the gestation length without correcting the offspring in utero growth restriction and catch-up growth caused by maternal obesity. Despite similar body weight, the 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 the 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.Description
Keywords
Metformin, Sex differences, Gestational Diabetes, White Adipose Tissue, Maternal Obesity, Foetal Programming
Journal Title
International journal of molecular sciences
Conference Name
Journal ISSN
1422-0067
Volume Title
22
Publisher
Publisher DOI
Sponsorship
Medical Research Council (MC_UU_00014/4)
British Heart Foundation (FS/16/53/32729, RG/17/12/33167, PG/13/46/30329)
British Heart Foundation (FS/16/53/32729, RG/17/12/33167, PG/13/46/30329)