Oral Presentation Australian and New Zealand Obesity Society Annual Scientific Conference 2024

Exploring the impact of maternal weight loss on metabolic function in offspring adipose tissue (#24)

Michelia Yu 1 , Natassia Rodrigo 1 2 3 4 , Amanda Purcell 1 , Sonia Saad 1 , Carol Pollock 1 , Sarah Glastras 1 2 3
  1. Kolling Institute, University of Sydney, Camperdown, NSW, Australia
  2. Northern Precinct, Sydney Medical School, University of Sydney, Sydney, NSW, Australia
  3. Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital , St Leonards, NSW, Australia
  4. Department of Diabetes and Endocrinology, Nepean Hospital, Nepean Hospital, Sydney, NSW, Australia

Background and Aims: Maternal obesity affects 1 in 5 women of reproductive age, having detrimental effects on maternal and offspring health outcomes. Offspring born to mothers with obesity have an increased risk of foetal overgrowth, rendering them more susceptible to developing metabolic diseases like type 2 diabetes, cardiovascular and liver diseases. Maternal weight loss interventions improve maternal outcomes, however, the effect on offspring outcomes remains largely unexplored. We aimed to determine whether maternal perinatal weight interventions, with either diet or pharmacology, improves offspring adipose tissue metabolic outcomes.

Methods: A diet-induced obesity mouse model was used; female C57BL/6 mice were fed either a high fat diet (HFD) or chow diet for 8 weeks. Then, the HFD-fed dams were allocated to 3 groups: HFD+liraglutide (0.3mg/kg), HFD switch to chow, or continuation of HFD for 4 weeks before pregnancy. After conception, a further group of HFD-fed dams were switched to chow. All male offspring were weaned to HFD, and at postnatal week 12, offspring epididymal white adipose tissue (eWAT) were collected. Real-time PCR, immunohistochemistry and western blot were used to investigate changes in inflammatory, oxidative stress, lipid, and fibrotic markers.

Results: Male offspring born to HFD-fed dams and HFD+liraglutide dams had significantly higher body weight and eWAT mass compared to offspring born to chow-fed dams. Offspring from HFD-fed dams also had elevated oxidative stress and fibrosis gene markers, compared to offspring born to chow-fed dams. Pre-pregnancy liraglutide treatment significantly reduced gene expression in lipid metabolism, oxidative stress, and fibrotic markers. Pre-conception diet modification also decreased offspring body weight, serum insulin, and metabolic markers.

Conclusion: Maternal weight intervention with either liraglutide or diet modification before pregnancy effectively ameliorates dysfunctional adipose tissue in offsprings, supporting ongoing public health messages for women with obesity to undergo weight interventions before pregnancy and interpregnancy for improved offspring outcomes.