Oral Presentation ESA-SRB-ANZOS 2025 in conjunction with ENSA

Pre-pregnancy liraglutide does not prevent the post-pregnancy adverse cardiovascular effects of maternal obesity in a murine model of obesity  (128742)

Matilda S G Longfield 1 2 , Carys Campbell 1 2 , Jessica Baldwin 2 , Natassia Rodrigo 1 2 3 , Melanie White 4 , Sarah J Glastras 1 2 5
  1. Diabetes, Metabolism & Endocrinology, Royal North Shore Hospital, Sydney, NSW, Australia
  2. Kolling Institute, University of Sydney, Sydney, NSW, Australia
  3. Department of Endocrinology, Nepean Hospital, Sydney, NSW, Australia
  4. Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia
  5. Northern Precinct, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia

Background: Obesity during pregnancy heightens cardiovascular disease (CVD) risk in women by compounding the physiological demands of pregnancy, such as increased blood volume and altered cardiac output. Current recommendations advise pre-pregnancy weight loss. GLP-1 receptor agonists show promise in weight management with improved cardiovascular outcomes, but their use pre-pregnancy remains understudied.  

Aim: To characterise the effects of pre-pregnancy liraglutide treatment on post-pregnancy cardiac protein expression in a murine model of high-fat diet–induced obesity. 

Methods: Female C57BL/6 mice were allocated to either a high-fat-diet (HFD) or chow-diet (CHOW). Liraglutide treatment (LIRA) commenced for a subset of the HFD group, after 8-weeks of diet commencement, at a dose of 0.3mg/kg. All other mice received volume matched saline. Female mice were co-housed with male mice until pregnancy was achieved, and after birth and lactation they were sacrificed (n=4/group/timepoint). Hearts were perfused with phosphate buffered saline before being snap frozen whole. After homogenisation and sample preparation proteomic analysis was completed on cardiac tissue using data-dependant acquisition, liquid chromatography mass spectrometry. Statistical analysis was completed in Spectronaught and R. 

Results: In total 31 proteins were significantly different post-pregnancy between the HFD and CHOW groups. Of these 15 were significantly up-regulated and 16 were significantly down-regulated (Adj.p<0.05). Whilst both tensin 1 and Succinate-dehydrogenase-assembly-factor 3 were approximately 2-fold increase in both the CHOW and LIRA groups comparted to HFD (Adj.p<0.05), 17 of the proteins dysregulated between HFD and CHOW followed the same pattern when comparing LIRA to CHOW (Adj.p<0.05). These proteins were significantly associated with several metabolic and oxidative pathways (p<0.05).  

Conclusion: Pre-pregnancy liraglutide treatment led to minimal changes in cardiac protein expression, suggesting limited cardioprotective effects after pregnancy. In contrast, the chow-fed group showed widespread alterations in protein expression, highlighting the greater impact of baseline metabolic health on postpartum cardiovascular outcomes.