Oral Presentation Australian and New Zealand Obesity Society Annual Scientific Conference 2023

The effect of weight loss, before or during pregnancy, in mothers with obesity, on structural and metabolic changes of offspring adipose tissue. (98308)

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, and it has detrimental effects on both 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 such as type 2 diabetes, cardiovascular diseases, and metabolic-associated fatty liver disease. Maternal weight loss interventions improve maternal fertility and reduce birth complications, however, the effect on offspring metabolic outcomes remains largely unexplored. We aimed to determine whether maternal pre-pregnancy or interpregnancy weight intervention, with either diet or pharmacological intervention, improved metabolic markers within adipose tissue of the offspring.

Methods: A diet-induced obesity mouse model was used; female C57BL/6 mice were fed either a high fat diet (HFD) or normal 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 13, offspring epigonadal adipose tissue (eWAT) was collected. Real-time PCR, and immunohistochemistry were used to investigate changes in inflammatory, oxidative stress, lipid, and fibrotic markers.

Results: Male offspring born to HFD-fed dams had elevated gene and protein markers of inflammation (MCP-1), oxidative stress (HIF-1a), lipid metabolism (PPARg) and fibrosis (collagen IV, CCN2), compared to offspring born to chow-fed dams. Pre-pregnancy diet modification and liraglutide treatment protected the offspring from these adverse foetal programming effects.

Conclusion: Maternal weight interventions for obesity, either before or during pregnancy, effectively ameliorate dysfunctional adipose tissue in the offspring. This supports ongoing public health messages to target women with obesity to undergo weight intervention strategies before pregnancy, and also provides evidence for interpregnancy interventions for improved offspring outcomes.