Thursday · Oct 8
9:00 - 11:00

Food for Thought: How diet composition impacts on brain functions in adult rodents and their offspring

Maria Florencia Rossetti

Institute of Health and Environment of Litoral (ISAL), CONICET-UNL, Department of Clinical Biochemistry. Faculty of Biochemistry and Biological Sciences, National University of Litoral (UNL). Province of Santa Fe. Argentina.

The rapid increase in the incidence of obesity and associated diseases during the last decades is primarily attributed to excessive consumption of palatable, energy-dense diets, including high-fat and high-fat/high-sugar diets, combined with sedentary lifestyles. Importantly, these diets have critical effects on brain and mood, including brain inflammation, homeostatic system disturbance, synaptic and behavioral plasticity decline and social deficits. Moreover, the offspring could also be influenced by the maternal nutritional experience during critical periods of fetal and early postnatal development. In this sense, the exposure to a maternal diet dominated by palatable food and/or high-fat diet before and during pregnancy and throughout lactation, disturbs glucose and lipid homeostasis, predisposes to adiposity, unbalances the gut microbiota, modifies food preference and alters the development of the central reward circuitry in the offspring after birth and later in life. In this context, the goal of the symposium is to engage the audience in a lively discussion about recently published and unpublished findings related to the impact of diet composition on brain functions, focusing on food intake control and cognition, in adult rodents and their offspring. We will explore genomic, hologenomic and behavioral alterations to elucidate possible new mechanisms involved on these functions and to identify potential therapeutic targets for metabolic and neurodevelopmental disorders.

The impact of a high fat diet on cognition and hippocampal function

Andreza de Bem

Universidade de Brasilia

Worldwide, especially in Western civilizations, most of the staple diets contain high amounts of fats, carbohydrates and comparatively low quantities of protein, leading to the increasing number of overweight and obese individuals. The well recognized association between energy dense diets and metabolic disorders also leads to an increasing investigation of its impact on the brain, behavior and cognition. Ous studies show that mice recognition memory and mood behavior are compromised after a shot time of HFD. Besides these changes are accompanied by increased BBB permeability and by reduction on synaptic plasticity. Hippocampal mitochondrial function is also affected, even after a longer period of HFD consumption, as well as astrogliosis. An early overexpression of proinflammatory cytokines (TNF-a and IL-6) occurs, and when treated with the anti-inflammatory drug, Infliximab, behavioral and BBB alterations were prevented. These results indicate rapid effect of the consumption of HFD leading to cognition and mood disorders, possibly by disrupting BBB homeostasis, a process that contribute to neuroinflammation. These findings have important implications for the contribution HFD intake to the development of neurodegenerative disorders.

Transgenerational effects of maternal high-fat diet: role of the microbiome

Shelly Buffington

The University of Texas of Medical Branch

Behavioral phenotypes are determined not only by the host genome, but by the hologenome, the combination of host and microbial genes. Gut microbiota are emerging as key regulators of both normal nervous system physiology and disease states. Working in the maternal high-fat diet model of autism, we recently identified a single bacterial species, Lactobacillus (L.) reuteri, which rescues social dysfunction and related deficits in social reward circuit plasticity. Specifically, we found that MHFD exposure induces long-term, functional changes in the offspring gut microbiome associated with dysregulation of the oxytocinergic system, deficits in social interaction-induced long-term plasticity in ventral tegmental area dopaminergic neurons, and resulting social impairments. Reconstitution with L. reuteri restored oxytocin levels, interaction-induced VTA plasticity, and social behavior in the offspring. In a follow-up study, we showed that L. reuteri rescues social dysfunction in multiple models of ASD of diverse pathoetiology (i.e., environmental, idiopathic, and genetic models) and that this rescue depends on vagus nerve integrity and oxytocin receptor signaling in dopaminergic neurons. Finally, I will present data from our ongoing investigation into how the MHFD-induced changes in the maternal gut microbiome alter maternal immune function and affect offspring brain development. Our findings identify the gut microbiome as a therapeutic target for neurodevelopmental disorders.

Cafeteria diet induces progressive changes in hypothalamic mechanisms involved in food intake control over time

Gisela Paola Lazzarino

Linköping University

To elucidate progressive hypothalamic changes in the development of obesity, we studied the effects of a highly palatable ‘junk-food’ cafeteria diet (CAF) intake from weaning on the mRNA levels and DNA methylation state of feeding-related neuropeptides and hormone receptors in individual hypothalamic nuclei at different feeding periods. A short-term of CAF increased energy intake and adiposity, without affecting neuropeptides’ expression. In the medium-term, the greater energy intake of CAF led to increased adiposity, hyperleptinemia, and overweight, related to an orexigenic response of lateral hypothalamus, and paraventricular and ventromedial nuclei, given principally by the upregulation of Orexins, Agouti Related Protein, and Neuropeptide Y. The arcuate nucleus displayed an anorexigenic signal with higher Proopiomelanocortin expression, not sufficient to keep the energy intake under regular values. Most of the changes in neuropeptidic mRNA levels induced by CAF were related to epigenetic modifications in their promoter regions. Metabolic and molecular changes were intensified in the long-term. These results showed that the hypothalamic energy homeostatic system is disrupted after a CAF medium-term intake, presumably through epigenetic mechanisms, leading to the development of obesity.The alterations observed in these hypothalamic nuclei could add information about their differential role in food intake control and how their action is disrupted in the development of obesity

Short-term, long-term and transgenerational effects of a highly palatable ‘junk-food’ diet on the mesolimbic system

María Florencia Andreoli

Instituto de Desarrollo e Investigaciones Pediátricas (IDIP) "Prof Dr Fernando Viteri" Hospital de Niños de la Plata - Min de Salud/Comisión de Investigaciones Científicas CIC-PBA

We studied the effects of a palatable ‘junk-food’ cafeteria diet (CAF) on the expression of key genes of the mesolimbic system, evaluating short-term, long-term and transgenerational effects in female rats. In the short term (30 days) CAF intake deregulated the dopamine (DA) pathway increasing the expression of DA transporter (DAT) in ventral tegmental area (VTA) with decreased methylation status of its promoter and decreasing DA receptor (DRD) 2 expression in accumbens nucleus (NAc). These alterations reflect a reduced DA signalling which could promote excessive intake of palatable foods. However, in the long term (80 days CAF) the changes were reversed. The effects were transmitted to the offspring involving epigenetic mechanisms. At PND10, maternal CAF decreased the transcription of tyrosine hydroxylase (TH), DRD2 and DAT in VTA with changes in the methylation status of their promoters. In NAc, maternal CAF diet reduced DRD1, DRD2 and DAT expression in the offspring, although changes in the methylation patterns were only detected in DAT promoter. A decrease in DA synthesis by TH and reduced actions through its receptors suggest a reduced DA signalling more pronounced than in the dams. These results provide novel insights about how junk-food can affect the reward system through life and in the early postnatal life of the offspring. Particularly important is the expression decline of DRD2 given its physiological implication in obesity and addiction.