Perinatal Semaglutide Treatment Improves Maternal and Offspring Metabolic Health in Obese Mice

The global rise in obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD) in children is partly attributed to early-life exposures, particularly maternal obesity and insulin resistance, which program offspring metabolic risk during critical developmental windows. Current interventions often target adult disease, leaving a gap in strategies to prevent the intergenerational transmission of metabolic dysfunction. GLP-1 receptor agonists (GLP-1 RAs) like semaglutide are potent metabolic regulators, making them candidates for early intervention to improve both maternal and offspring metabolic health.

Researchers evaluated semaglutide administered from preconception through lactation in dams fed a high-fat diet (HFD) or standard diet. Offspring were subsequently weaned to a standard diet. The study assessed maternal body composition and glucose metabolism during pregnancy and 10 weeks post-weaning. Offspring glucose homeostasis and hepatic steatosis were evaluated at 18 weeks of age. Additionally, conception rate and fetal viability were monitored to assess safety.

Maternal semaglutide treatment significantly improved body composition and glucose metabolism in HFD-fed dams during pregnancy. These beneficial maternal metabolic changes persisted for 10 weeks after weaning, even after treatment discontinuation. Offspring exposed to maternal HFD exhibited impaired glucose homeostasis and promoted hepatic steatosis at 18 weeks of age. However, these adverse effects were ameliorated by maternal semaglutide treatment. Importantly, metabolic improvements in both dams and offspring occurred without any adverse effects on conception rate or fetal viability, suggesting a safe perinatal intervention. The study highlights the potential of targeting the GLP-1R pathway during early development.

Maternal semaglutide ameliorated the impaired glucose homeostasis and hepatic steatosis observed in offspring at 18 weeks of age, which were otherwise caused by maternal HFD exposure.