Defense title: "Study of the influence of sex as a potential  variable in the predisposition to metabolic disorders"

In front of the following jury members:

Dr. Susan OZZANE

Dr. Paola CASANELLO

Dr. Khadija OUGUERRAM

Dr. Maria Luisa LAZO DE LA VEGA MONRROY

Dr. Gloria BARBOSA SABANERO

Dr. Silvio ZAINA

The defense in a few words: 

Maternal or paternal obesity increases the risk in the offspring to develop metabolic diseases and cognitive disorders via a "metabolic programming" process underpinned by epigenetic modifications. The physiological disturbances resulting from metabolic programming evolve with age, may be transgenerational, and vary as a function of sex. In this thesis, we analysed the molecular mechanisms involved in the metabolic and cognitive alterations exhibited by adult male and female rats with a history of maternal (MO) or paternal (PO) obesity. Our data show that memory deficits induced by either MO or PO are associated with impaired glutamate-mediated synaptic plasticity, which may result from reduced expression of NMDA receptors, increased brain concentrations of kynurenic acid (KN) and quinolinic acid (QA), and increased synthesis of sphingolipids. We also found significant gender differences in liver lipidoma, in particular with reduced ceramide synthesis in female rats compared to male rats. These gender differences are due to the presence at higher levels in female animals of the inhibitory epigenetic mark H3K27me3 on the promoter site of the gene coding for the enzyme that catalyses the first stage of sphingolipid synthesis. This epigenetic mark determines the differential response of male and female animals to a high-calorie diet, as well as their response to maternal or paternal obesity.