Hippocampus network in response to visual food cues in children and adults: Influence of maternal metabolism and central insulin action

Abstract

Pediatric obesity significantly impacts brain development, with GDM being one of the contributing factors. GDM exposes the fetus to hyperinsulinemia, which alters brain responses to endogenous insulin and suggests impaired central insulin action. Insulin signaling in the brain plays a crucial role in cognitive function and appetite regulation. The hippocampus, a critical region for cognition and food intake, is particularly vulnerable to adverse prenatal environments and is highly sensitive to insulin. However, the response of hippocampal network to chronic hyperinsulinemia exposure (from GDM) and acute exogenous insulin during food cue processing remains unclear. Firstly, this thesis systematically reviews neuroimaging studies in children and adolescents with obesity to identify brain alterations and explore the impact of obesity-promoting factors, like GDM, on brain development. The influence of obesity on brain structure and function, particularly in the hippocampus, amygdala and basal ganglia within the mesocorticolimbic circuitry, varies cross developmental stage. Maternal obesity and GDM influence brain development independent of the child’s current weight status. Secondly, fMRI was used to assess hippocampal network during a food cue task in children aged 7–11 years, comparing those exposed to GDM with those not exposed. Associations between BMI and hippocampal network were analyzed in both groups. Children with GDM exposure showed stronger functional connectivity between the hippocampus and reward processing regions. An association between the adiposity and hippocampal functional connection to the somatosensory cortex was only observed in GDM group. These changes suggest that intrauterine GDM exposure leads to long-lasting effects on the hippocampal network, potentially increasing the risk of future weight gain and metabolic disorders. This highlights the importance of early interventions for adverse prenatal exposures due to their long-term effects on brain development. Thirdly, the response of hippocampal network to intranasal insulin during food cue processing was explored in adults using fMRI. The influence of sex hormone levels on hippocampal functional connectivity was assessed in premenopausal women. Central insulin increased hippocampal functional connectivity with the inhibitory control region, supporting insulin’s anorexic effect. Sex differences were observed in the functional connectivity between the hippocampus and visual cortex, potentially related to sex hormones fluctuation in women. These findings suggest that individualized interventions for central insulin resistance conditions, accounting for sex-specific responses, may provide additional benefits.

Die Dissertation ist gesperrt bis zum 31. Dezember 2025 !