Oral Presentation ESA-SRB-AOTA 2019

The effect of preconception metabolic optimisation on end organ inflammation in late gestation mice. (#249)

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 affects 20% of pregnant women and negatively impacts metabolic health in mothers. 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 inflammation is emerging as a crucial factor. To date, no studies have addressed whether pre-conception maternal weight loss improves inflammatory markers in obese mothers. We aimed to determine if weight loss prior to pregnancy, either with diet modification or liraglutide treatment, improves maternal metabolic outcomes and reduces inflammation in maternal blood, placenta and liver. 

 

 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 measure tissue-specific metabolic profiles together with inflammatory markers including TGF-b, IL-6 and hs-CRP.

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. Liver and placental inflammatory markers and metabolic markers were improved in the intervention groups compared to the non-treated HFD-fed group.  

Conclusions: Preconception weight loss can improve maternal weight leading into pregnancy. It further improves maternal insulin resistance, organ inflammation and metabolic markers.