PhDAmandine Lépinay

Programming effects of maternal high-fat diet and early stress on adult phenotype

December 17, 2014

The perinatal period is a critical period during which the quality of the environment has long lasting effects on adult phenotype. Early adversity in childhood has been associated with higher risks to develop neuropsychiatric disorders later in life. Nowadays, modern societies are characterized by a high consumption of fat. Although these changes also affect nutritional environment during development, the impact on brain functioning and behavior remains unknown.

The aim of my thesis was to examine the programming effects of maternal high-fat diet (HFD, western diet) and early stress on offspring phenotype. In the first part, we showed that maternal HFD leads to metabolic disturbances in adult offspring and sensitized to memory deficits if the HFD is maintained throughout life. In the second part, we explored the effects of the combination between maternal HFD and chronic maternal separation (3h/day, postnatal day 2 to 14). Maternal separation enhances motivation for palatable food and combined with maternal HFD exacerbates vulnerability to diet-induced obesity. In contrast, maternal HFD protects the offspring against the emotional and cognitive impairments induced by maternal separation.
This protective effect of maternal HFD could be related to the increase of maternal care in stressed dams exposed to HFD and to the attenuation of neurodevelopmental alterations in the prefrontal cortex of stressed pups. In conclusion, my work demonstrates that stress and nutrition during early life interact and influence later adult phenotype.

Keywords : motivation, metabolism, emotion, memory

Lépinay A.L, Larrieu T., Joffre C., Acar N., Garaté I., Castanon N., Ferreira G., Langelier B., Guesnet P., Bretillon L., Parnet P., Layé S., Darnaudéry M., Perinatal western diet increases hippocampal vulnerability to the adverse effects of subsequent high-fat feeding in rats. Psychoneuroendocrinology, en révision 

Lépinay A.L, Alonso L., Caillé-Garnier S., Cador M., Layé S., Darnaudéry M., Impact of a perinatal high-fat diet combined with maternal separation on response to nutritional challenges and food motivation in offspring, en cours de soumission (Frontiers in behavioral Neuroscience)

Lépinay A.L, P. Delage, M. Rincel, J. Fioramonti, V. Theodorou, S. Layé, M. Darnaudéry, Maternal high-fat diet counteracts the neurodevelopmental and long lasting deleterious effects induced by maternal separation, en cours de soumission (Neuropsychopharmacology)

PhD committee

  • Dr Sophie Layé
    INRA, Bordeaux, Présidente
  • Dr Valérie Daugé
    INRA, Jouy en Josas, Rapportrice
  • Pr Stefania Maccari
    CNRS, Université de Lille, Rapportrice
  • Pr Vassilia Théodorou
    INRA, Ecole d’ingénieur de Purpan, Toulouse, Examinatrice
  • Dr Susanna Pietropaolo
    CNRS, INCIA, Bordeaux, Examinatrice
  • Pr Muriel Darnaudéry
    INRA, Université de Bordeaux, Directrice de thèse

Thesis supervisor

Muriel Darnaudery
Professor of Neuroscience

University of Bordeaux 
lab NutriNeurO- 

Last update: 17 December 2014