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

Area of Science:

• Neuroscience
• Metabolic disorders
• Developmental biology

Background:

• Obesity and diabetes are linked to neurodegeneration.
• Brain glucose metabolism and brain-derived neurotrophic factor (BDNF) are crucial for perinatal brain development.
• BDNF influences brain health, appetite, and glucose regulation.

Purpose of the Study:

• To investigate the relationship between glycemia, brain glucose utilization, obesity, and BDNF levels in Zucker rats and human infants.
• To determine if altered glucose metabolism precedes obesity and impacts BDNF in early life.

Main Methods:

• ¹⁸FDG-PET scans were used to measure brain glucose utilization in Zucker rats during fasting and glucose loading.
• Blood glucose, BDNF, and appetite-regulating hormones were measured in rats and human infants.
• Maternal and fetal factors, including glycemia, were assessed in human pregnancies.

Main Results:

• Zucker rats exhibited glucose intolerance and increased brain glucose utilization, even before obesity onset.
• Higher glycemia and age were associated with increased brain glucose utilization and decreased BDNF levels.
• In humans, fetal glycemia correlated with maternal glycemia and predicted lower BDNF levels; leptin was linked to higher body weight and lower BDNF.

Conclusions:

• Glucose intolerance and elevated brain glucose utilization occur early in life, preceding obesity in Zucker rats.
• Elevated glucose levels and brain glucose overexposure from perinatal stages predict reduced circulating BDNF.
• Controlling maternal and fetal glycemia during intrauterine development may prevent adverse neurodevelopmental interactions.