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

Liraglutide ameliorates pathogenic changes in cardiac tissue proteins in female mice of reproductive age   (128695)

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 increases the risk of cardiovascular disease among women of reproductive age, highlighting the need for intervention strategies to address this understudied population. GLP-1 receptor agonists, such as liraglutide, are effective therapeutic options for weight reduction, yet their cardiovascular impacts in women of reproductive age remain understudied.  

Aim: To employ untargeted proteomic analysis to characterise the protein differences in cardiac tissue in female mice of reproductive age, exposed to an obesogenic environment.  

Methods: 6-week-old female C57BL/6 mice were allocated to either a high-fat-diet (HFD) or chow-diet (CHOW). After 8-weeks, the HFD-fed group was further randomised to receive subcutaneous injections of liraglutide (LIRA), 0.3mg/kg daily, or matched saline.  Mice were sacrificed after 4-weeks of treatment with LIRA or saline and the 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 46 proteins were significantly different between the HFD and CHOW groups. Of these 37 were upregulated, and 9 were downregulated  (Adj.p<0.05).  Immunoglobulin-heavy-constant-gamma 3 was 1.6-fold lower in HFD vs both CHOW and LIRA (p<0.05). Both Immunoglobulin-heavy-constant-gamma 2C and Immunoglobulin-heavy-variable 1-77 were >2-fold higher in HFD vs both CHOW and LIRA (Adj.p<0.05). Furthermore, 32 proteins that were significantly different between CHOW and HFD were not significantly different in the LIRA group compared to CHOW or HFD suggesting some level of amelioration. These proteins were significantly associated with the regulation of triglyceride metabolic process (p<0.05).  

Conclusion: Our findings indicate that 4-weeks treatment with liraglutide modulates specific protein expression, indicating potential mechanisms for its cardiometabolic benefits. Given the heightened cardiovascular risk in women of reproductive age with obesity, further study of GLP-1 receptor agonists in this group is warranted.