Oral Presentation ANZOS-ASLM-ICCR 2019

The effect of preconception weight modulation strategies on maternal metabolic outcomes in late gestation mice (#92)

Natassia Rodrigo 1 2 , Jasmin Russell 3 , Hui Chen 3 , Carol Pollock 2 4 , Sarah Glastras 1 2
  1. Endocrinology, Royal North Shore Hospital, St Leonards, NSW, Australia
  2. University of Sydney, Sydney, NSW, Australia
  3. University of Technology, Sydney, Sydney, NSW, Australia
  4. Renal Department, Royal North Shore Hospital, Sydney, NSW, Australia

Background and aims:

 Maternal obesity is a growing concern among pregnant women, with adverse effects on metabolic health. Maternal complications include gestational diabetes, preeclampsia, fatty liver disease and increased rates of cardiovascular disease. Whilst the mechanisms underlying these complications are not fully elucidated, metabolic dysregulation is fundamental to this pathophysiologic process. To date, no studies have addressed whether pre-conception maternal weight loss improves metabolic markers in obese mothers. We aimed to determine if weight loss prior to pregnancy, either with diet  modification or liraglutide therapy, improves maternal metabolic outcomes and alters subsequent pregnancy outcomes. 

Materials and Methods:

Maternal obesity was modelled in C57BL/6 mice; with dams fed a high fat diet (HFD) versus chow diet for 8 weeks and compared to lean chow-fed controls. In obese dams, liraglutide (0.3mg/kg, s.c., for 4 weeks) or diet modification (switch to chow) was utilised to induce pre-conception weight loss. Pregnancy rates were observed after mating. Maternal anthropometric measures, glucose tolerance and metabolic markers were measured before and 1 week after intervention, and at late gestation. Pregnant dams were sacrificed at gestational Day 18-20 and maternal blood, liver and placenta were collected. Immunohistochemistry, western blotting and real-time PCR were used to determine tissue-specific metabolic profiles in blood, liver and placenta.

Results:

HFD-fed dams had greater weights and reduced glucose tolerance compared to chow-fed dams. Following intervention with liraglutide or diet modification, insulin resistance and body weight were reduced.  Weight intervention with either liraglutide or diet improved conception rates and normalised foetal number in HFD-fed dams. Blood, liver and placental metabolic markers were improved in the intervention groups compared to the non-treated HFD-fed group.  

Conclusions:

Preconception weight modulation strategies are effective in altering maternal weight prior to pregnancy, with ensuing alterations in pregnancy outcomes. It further improves maternal metabolic profiles.