A high fat diet modifies brain neurotransmitter profile and hippocampal proteome and morphology in an IUGR pig model

ABSTRACT: Intrauterine Growth Restriction (IUGR) is a pathological condition that hinders the correct growth of the foetus during pregnancy due to oxygen or nutrient deficiency. Consequently, the foetus adapts its metabolism and physiology to survive in such scarce environment. The major adaptation is the so called “brain sparing”; this effect gives priority to brain development to ensure the individual survival. Nevertheless, this does not warrant the normal development of the brain and the risk exists of neurological and cognitive deficits at short or long term. In turn, this adaptation leads to other systemic alterations that affect the energetic metabolism, thus inducing the emergence of a fairly characterized phenotype called “thrifty phenotype”. This phenotype is responsible for the metabolic alterations that last up until adulthood, which increase the incidence of some diseases like diabetes and metabolic syndrome. On the other hand, diets rich in fat are known to exert pernicious effects Using a pig model of IUGR, animals are classified as normal birth weight (NBW) or low birth weight (LBW). We have studied the effect of a long-term high fat diet (HFD) on the neurological alterations regarding the neurotransmitter profile in several brain areas, the morphology of the hippocampus and the proteome of this same brain area. Our hypothesis is that those animals that were affected by IUGR during their gestation, and therefore were born LBW, will present a different susceptibility to a HFD than NBW animals when they become adults. Our results indicate that HFD had a significant effect on the neurotransmitter profile of the hippocampus, amygdala, hypothalamus, striatum and prefrontal cortex. The most affected neurotransmitter was serotonin (5-HT), thus affecting the indolamine pathway. On the other hand, HFD does not provoke relevant changes in the morphology of the hippocampus. Finally, the proteomic analysis revealed that, in some instances, NBW and LBW animals respond to HFD in different ways. In particular, NBW animals present changes in the mitochondrial respiratory chain and oxidative phosphorylation, and in the extracellular matrix and its interaction with the cell. LBW animals present differences in RNA splicing, anterograde and retrograde transport and the mTOR pathway.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Sus Scrofa Domesticus (domestic Pig)

TISSUE(S): Brain

SUBMITTER: Marina Gay  

LAB HEAD: Anna Bassols

PROVIDER: PXD032300 | Pride | 2022-10-14

REPOSITORIES: Pride