Aims
Obesity prevails as one of the leading risk factors for a variety of health conditions, inclusive of type 2 diabetes, cancer and heart disease. For women, these co-morbidities extend to complications affecting menstruation and fertility, together with adverse complications in pregnancy and poor kidney outcomes long-term. Our study aims to determine whether pre-pregnancy use of liraglutide in obese mice will induce weight loss and improve conception rates, improve glucose tolerance in late gestation and foetal survival and reduce kidney damage.
Methods
C57BL6 dams were fed either high fat died (HFD) or chow and administered liraglutide (0.3mg/ml s.c. daily for 4 weeks duration) versus vehicle control prior to conception. An intraperitoneal glucose tolerance test (IPGTT) was performed prior to and following the drug or vehicle administration. Dams were co-housed with a chow-fed male and once pregnancy was confirmed, a further IPGTT was performed in late gestation. Kidneys were collected on gestational day 18 and histological examination together with western blotting and RT-PCR was performed.
Results
HFD-fed dams receiving liraglutide compared to vehicle control had reduced body weight prior to pregnancy. They also had improved glucose tolerance prior to pregnancy and improved pregnancy rates. The animals with lover body weight at conception had reduced markers of inflammation and oxidative stress in the kidneys at late gestation.
Conclusions
Liraglutide shows promise in being repurposed from an anti-obesity and diabetes treatment to being a useful adjunct for obese women desiring pregnancy with improvements in maternal glucose tolerance, conceptions rates and kidney health. Moreover, reduced body weight in pregnancy facilitated by pre-pregnancy administration of liraglutide may improve kidney-related complications such as gestational hypertension and preeclampsia.