Early life exposure to high fructose diet induces metabolic dysregulation associated with sex-specific cognitive impairment in adolescent rats

Barrett, Chris; Jiang, Megan; O'Flaherty, Brendan G; Dias, Brian; Rainnie, Donald G.; Young, Larry J.; Menigoz, Aurelie

doi:10.1016/j.jnutbio.2022.109220

Cited by 4 publications

(2 citation statements)

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“…From comparing populations exposed to SEEs and matched controls, we have data showing that exposures as diverse as substance abuse by pregnant mothers, high sugar diets during infancy, parental economic scarcity, and social isolation in adolescence result in departures from typical trajectories of development as measured by brain thickness, excitatory/inhibitory balance, and connectivity between brain regions (136)(137)(138)(139)(140)(141)(142). Complementing these studies in humans, work in mice and rats demonstrates accelerated and decelerated trajectories of synaptic pruning, emergence of molecular contributors to excitatory/inhibitory balance in the aftermath of fetal alcohol exposure, ingestion of high sugar diets in infancy, and social isolation in adolescence (143)(144)(145)(146)(147). There is also steadily accumulating data that racial trauma and discriminative practices affect neuroanatomy in the generations directly exposed to these atrocities (148).…”

Section: Epigeneticsmentioning

confidence: 98%

Towards understanding and halting legacies of trauma

Taylor,

Korobkova,

Bhinderwala

et al. 2024

Preprint

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Echoes of natural and anthropogenic traumas not only reverberate within the physiology, biology, and neurobiology of the generation directly exposed to them but also within the biology of future generations. With the intent of understanding this phenomenon, significant efforts have sought to establish multi-generational legacies of experiences like stress, chemical exposures, nutritional impoverishment, and chemosensory experiences. From these studies, we are gaining new appreciation for how legacies of trauma come to be bequeathed to future generations. This review first outlines principles that merit attention in the study of multi-generational legacies of trauma. Next, it discusses causes and consequences that allow for such legacies to perpetuate across generations. Finally, we discuss silver linings of such legacies and how legacies of flourishing can be engineered. In summary, this review synthesizes our current understanding of the concept, causes and consequences of legacies of trauma and looks to opportunities to halt them.

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Section: Epigeneticsmentioning

confidence: 98%

Towards understanding and halting legacies of trauma

Taylor,

Korobkova,

Bhinderwala

et al. 2024

Preprint

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“…Both synaptic pruning and the phagocytic clearance of dying neurons (termed efferocytosis) are executed by microglia, the CNS's resident macrophage and professional phagocyte 10,[36][37][38][39][40][41][42] . Importantly, disrupted synaptic pruning or the removal of dying neurons can have catastrophic consequences on neurodevelopment in animals, including the development of anxiety-like behavior [43][44][45][46][47][48] . Here, we investigated the hypothesis that early life high fructose directly affects essential microglia phagocytic processes and whether early life high fructose causes defects in learning and the development of anxiety-like behavior.…”

Section: Introductionmentioning

confidence: 99%

Early life high fructose exposure disrupts microglia function and impedes neurodevelopment

Wang,

Lipshutz,

Liu

et al. 2023

Preprint

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Despite the success of fructose as a low-cost food additive, recent epidemiological evidence suggests that high fructose consumption by pregnant mothers or during adolescence is associated with disrupted neurodevelopment. An essential step in appropriate mammalian neurodevelopment is the synaptic pruning and elimination of newly-formed neurons by microglia, the central nervous system (CNS) resident professional phagocyte. Whether early life high fructose consumption affects microglia function and if this directly impacts neurodevelopment remains unknown. Here, we show that both offspring born to dams fed a high fructose diet and neonates exposed to high fructose exhibit decreased microglial density, increased uncleared apoptotic cells, and decreased synaptic pruning in vivo. Importantly, deletion of the high affinity fructose transporter SLC2A5 (GLUT5) in neonates completely reversed microglia dysfunction, suggesting that high fructose directly affects neonatal development. Mechanistically, we found that high fructose treatment of both mouse and human microglia suppresses synaptic pruning and phagocytosis capacity which is fully reversed in GLUT5-deficient microglia. Using a combination of in vivo and in vitro nuclear magnetic resonance- and mass spectrometry-based fructose tracing, we found that high fructose drives significant GLUT5-dependent fructose uptake and catabolism, rewiring microglia metabolism towards a hypo-phagocytic state. Importantly, mice exposed to high fructose as neonates exhibited cognitive defects and developed anxiety-like behavior which were rescued in GLUT5-deficient animals. Our findings provide a mechanistic explanation for the epidemiological observation that early life high fructose exposure is associated with increased prevalence of adolescent anxiety disorders.

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