Elevated glycemia and brain glucose utilization predict BDNF lowering since early life

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 (by (18)FDG-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.