Elena Sanguinetti1,2, Tiziana Liistro1, Marco Mainardi3,4, Silvia Pardini1, Piero A Salvadori1, Alessandro Vannucci5, Silvia Burchielli5, Patricia Iozzo6. 1. Institute of Clinical Physiology, National Research Council (CNR), via Moruzzi 1, Pisa, 56124, Italy. 2. Scuola Superiore di Studi Universitari Sant'Anna, Pisa, Italy. 3. Institute of Neuroscience, National Research Council (CNR), Pisa, Italy. 4. Institute of Human Physiology, Università Cattolica del Sacro Cuore, Rome, Italy. 5. Fondazione Toscana Gabriele Monasterio (FTGM), Pisa, Italy. 6. Institute of Clinical Physiology, National Research Council (CNR), via Moruzzi 1, Pisa, 56124, Italy. patricia.iozzo@ifc.cnr.it.
Abstract
AIMS/HYPOTHESIS: Maternal obesity negatively affects fetal development. Abnormalities in brain glucose metabolism are predictive of metabolic-cognitive disorders. METHODS: We studied the offspring (aged 0, 1, 6, 12 months) of minipigs fed a normal vs high-fat diet (HFD), by positron emission tomography (PET) to measure brain glucose metabolism, and ex vivo assessments of brain insulin receptors (IRβ) and GLUT4. RESULTS: At birth, brain glucose metabolism and IRβ were twice as high in the offspring of HFD-fed than control mothers. During infancy and youth, brain glucose uptake, GLUT4 and IRβ increased in the offspring of control mothers and decreased in those of HFD-fed mothers, leading to a 40-85% difference (p < 0.05), and severe glycogen depletion, lasting until adulthood. CONCLUSIONS/ INTERPRETATION: Maternal high-fat feeding leads to brain glucose overexposure during fetal development, followed by long-lasting depression in brain glucose metabolism in minipigs. These features may predispose the offspring to develop metabolic-neurodegenerative diseases.
AIMS/HYPOTHESIS: Maternal obesity negatively affects fetal development. Abnormalities in brain glucose metabolism are predictive of metabolic-cognitive disorders. METHODS: We studied the offspring (aged 0, 1, 6, 12 months) of minipigs fed a normal vs high-fat diet (HFD), by positron emission tomography (PET) to measure brain glucose metabolism, and ex vivo assessments of brain insulin receptors (IRβ) and GLUT4. RESULTS: At birth, brain glucose metabolism and IRβ were twice as high in the offspring of HFD-fed than control mothers. During infancy and youth, brain glucose uptake, GLUT4 and IRβ increased in the offspring of control mothers and decreased in those of HFD-fed mothers, leading to a 40-85% difference (p < 0.05), and severe glycogen depletion, lasting until adulthood. CONCLUSIONS/ INTERPRETATION: Maternal high-fat feeding leads to brain glucose overexposure during fetal development, followed by long-lasting depression in brain glucose metabolism in minipigs. These features may predispose the offspring to develop metabolic-neurodegenerative diseases.
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