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Maternal Metformin Intervention during Obese Glucose-Intolerant Pregnancy Affects Adiposity in Young Adult Mouse Offspring in a Sex-Specific Manner.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Schoonejans, Josca M  ORCID logo  https://orcid.org/0000-0003-2893-7199
Blackmore, Heather L  ORCID logo  https://orcid.org/0000-0003-0180-3852
Ashmore, Thomas J 
Aiken, Catherine E 
Fernandez-Twinn, Denise S  ORCID logo  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

foetal programming, gestational diabetes, maternal obesity, metformin, sex differences, white adipose tissue, Adiposity, Animals, Animals, Newborn, Diabetes, Gestational, Female, Male, Metformin, Mice, Mice, Inbred C57BL, Obesity, Maternal, Pregnancy, Prenatal Exposure Delayed Effects, Sex Factors

Journal Title

Int J Mol Sci

Conference Name

Journal ISSN

1661-6596
1422-0067

Volume Title

22

Publisher

MDPI AG

Rights

All rights reserved
Sponsorship
British Heart Foundation (RG/17/12/33167)
British Heart Foundation (None)
MRC (MC_UU_00014/4)
MRC (MR/T016701/1)
Medical Research Council (MC_UU_12012/4)
Medical Research Council (MC_PC_12012)