Modeling fructose-induced brain alterations: integrating in vivo and stem cell-based in vitro systems

The global consumption of sugars has markedly increased, driven by the widespread availability of sugar-sweetened beverages and processed foods enriched with high-fructose corn syrup. While the metabolic and inflammatory consequences of fructose overconsumption are well established, its impact on brain function, particularly during adolescence, is only beginning to emerge. This developmental window represents a critical period for brain maturation, and adolescents are among the most vulnerable due to their high intake of sugary foods. Our study aims to investigate the brain alterations induced by fructose consumption specifically during adolescence and to determine how long these changes can persist throughout development, even after a return to healthy dietary habits. To achieve this, we conduct in vivo experiments to examine the long-term effects of adolescent fructose exposure on brain function and behavior during growth. Furthermore, it remains unclear whether the neurological effects of fructose are mediated by direct actions on neural cells or through systemic indirect pathways. To address this, we take advantage of in vitro differentiation of embryonic stem cells into neurons and glial cells. This model offers a powerful system to assess the direct effects of fructose on neurogenesis and neural maturation, enabling us to dissect the cellular and molecular mechanisms underlying fructose-induced brain alterations. Together, these complementary approaches provide novel insights into the developmental neurotoxicity of fructose and its potential long-term consequences on brain health.