Conséquences de l’obésité maternelle sur le développement neural précoce chez le nouveau-né : le rôle potentiel de la leptine
Mélanie Brosset-Heckel
Team “Perinatal Imprintings and Neurodevelopental Disorders”

Abstract
Obesity and overweight, which are continuously increasing, constitute a major public health challenges affecting all populations, including women of childbearing age and pregnant women. Epidemiological and experimental data show that maternal obesity increases the risk of complications during pregnancy and is linked to the development of metabolic, nutritional, and neurodevelopmental disorders in offspring. However, the consequences of maternal obesity on neonatal brain development and the mechanisms involved are poorly understood.
Leptin, an adipocyte hormone involved in food intake, also regulates reproductive and cognitive functions. During development, its neurotrophic role is expressed by a gestational surge during the third trimester of pregnancy.
In the context of maternal obesity, maternal and neonatal hyperleptinemia may contribute to the development of neurodevelopmental disorders in offspring.
This thesis aimed to determine the impact of maternal obesity on early neural development, distinguishing the effects of pre-gestational obesity from those related to a perinatal obesogenic diet, while exploring sexual dimorphisms. The goal was to assess the role of leptin in alterations induced by maternal obesity.
Maternal obesity disrupts the balance of glutamatergic/GABAergic synaptic signaling in the hippocampus and delays the inhibitory GABA switch in both male and female offspring. These disturbances are prevented by returning to a so-called standard diet before gestation.
Consuming an obesogenic diet during pregnancy and lactation is sufficient to induce alterations in female offspring, while the effects observed in males are leptin dependent.

Jury
Sébastien BOURET, Rapporteur – LilNCog, Lille
Heather MCLEAN, Rapportrice – Institut NeuroPSI
Paolo GUBELLINI, Examinateur – CRPN, Marseille
Muriel DARNAUDERY, Examinatrice – Bordeaux Neurocampus
Christophe PORCHER, Président du jury – Inmed, Marseille
Jean-Luc GAÏARSA, Directeur de thèse – Inmed, Marseille

Wednesday 18 June 2025 at 2pm – Inmed conference room