title: Elevated glycemia and brain glucose utilization predict BDNF lowering since early life.
abstract: Obesity and diabetes associate with neurodegeneration. Brain glucose and BDNF are fundamental in perinatal development. BDNF is related to brain health, food intake and glucose metabolism. We characterized the relationship between glycemia and/or brain glucose utilization (by18FDG-PET during fasting and glucose loading), obesity and BDNF in 4-weeks old (pre-obese) and 12-weeks old (obese) Zucker fa/fa rats, and their age-matched fa/+ controls. In 75 human infants, we assessed cord blood BDNF and glucose levels, appetite regulating hormones, body weight and maternal factors. Young and adult fa/fa rats showed glucose intolerance and brain hyper-utilization compared to controls. Glycemia and age were positively related to brain glucose utilization, and were negative predictors of BDNF levels. In humans, fetal glycemia was dependent on maternal glycemia at term, and negatively predicted BDNF levels. Leptin levels were associated with higher body weight and lower BDNF levels. Glucose intolerance and elevated brain glucose utilization already occur in young, pre-obese rats, suggesting that they precede obesity onset in Zucker fatty rats. Glycemic elevation and brain glucose overexposure predict circulating BDNF deficiency since perinatal and early life. Future studies should evaluate whether the control of maternal and fetal glycemia during late intrauterine development can prevent these unfavorable interactions.
authors.affiliation: 1 Institute of Clinical Physiology, National Research Council (CNR), Pisa, Italy.
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Guzzardi
authors.affiliation: 1 Institute of Clinical Physiology, National Research Council (CNR), Pisa, Italy.|2 Scuola Superiore di Studi Universitari Sant'Anna, Pisa, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Sanguinetti
authors.affiliation: 1 Institute of Clinical Physiology, National Research Council (CNR), Pisa, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Bartoli
authors.affiliation: 3 Gynaecology and Obstetrics Department, Azienda USL Toscana Nord Ovest, Massa e Carrara, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Kemeny
authors.affiliation: 1 Institute of Clinical Physiology, National Research Council (CNR), Pisa, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Panetta
authors.affiliation: 1 Institute of Clinical Physiology, National Research Council (CNR), Pisa, Italy.
authors.forename: Piero A
authors.initials: PA
authors.lastname: Salvadori
authors.affiliation: 4 Fondazione Toscana Gabriele Monasterio (FTGM), Pisa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Burchielli
authors.affiliation: 1 Institute of Clinical Physiology, National Research Council (CNR), Pisa, Italy.
authors.forename: Patricia
authors.initials: P
authors.lastname: Iozzo
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000032:analysis*; D001921:Brain / Q000000981:diagnostic imaging; D001923:Brain Chemistry; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism; D019788:Fluorodeoxyglucose F18; D005838:Genotype; D005947:Glucose / Q000032:analysis / Q000378:metabolism*; D018149:Glucose Intolerance / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics / Q000378:metabolism; D007223:Infant; D007231:Infant, Newborn; D020738:Leptin / Q000097:blood; D008297:Male; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D049268:Positron-Emission Tomography; D051381:Rats; D011924:Rats, Zucker
chemical_list: C000628854:Bdnf protein, rat; D001786:Blood Glucose; D019208:Brain-Derived Neurotrophic Factor; D020738:Leptin; D019788:Fluorodeoxyglucose F18; C579455:BDNF protein, human; D005947:Glucose
keywords: BDNF; Glucose intolerance; brain glucose; childhood; positron emission tomography