Introduction and Aim: In Australia, approximately 35% of women of childbearing age have obesity. There is a strong link between maternal obesity and the programming of obesity and metabolic-associated fatty liver disease (MAFLD) in adult offspring, yet to date methods to alleviate this intergenerational onset of obesity and associated comorbidities remain largely unexplored. This study aimed to determine if perinatal weight loss, either by dietary intervention or the administration of the glucagon-like peptide-1 receptor agonist (GLP-1RA), liraglutide, improves adverse metabolic and liver health outcomes in the offspring of mothers with obesity.
Method: Mice were fed high-fat diet (HFD) for 8 weeks. Weight loss was induced by replacing HFD with chow diet (prior to, or during pregnancy) or by administering pre-pregnancy liraglutide. 8 dams continued on chow diet as controls and HFD for comparison. All the offspring were fed HFD post-weaning. The anthropometric and metabolic outcomes of the offspring were assessed at 12 weeks old.
Results: Body weight was significantly higher in the offspring of all maternal HFD-fed groups compared to the maternal chow-fed group, regardless of maternal weight change (p<0.01). The offspring of mothers with perinatal weight loss by dietary intervention had reduced insulin resistance (p<0.01) and hepatic gene expression of markers involved in inflammation (MCP-1, p<0.0001), oxidative stress (SOD1, p<0.001) and fibrosis (COL-1, -1V, p<0.05). A similar phenotype was observed in the offspring of mothers with perinatal weight loss via dietary intervention.
Conclusion: This study determined that both dietary intervention in the periconception period and pre-pregnancy liraglutide are advantageous in the context of ameliorating liver health outcomes in offspring providing crucial evidence for prospective mothers of the powerful effect that maternal weight intervention has on offspring health.