The fasting polypeptide FGF21 can enter brain from blood

Area of Science:

• Neuroscience
• Endocrinology
• Physiology

Background:

• Fibroblast growth factor 21 (FGF21) is implicated in fasting metabolism.
• Its direct transport to the brain remains uncharacterized.
• Understanding FGF21's brain penetration is crucial for its physiological role.

Purpose of the Study:

• To quantify the influx rate of FGF21 across the blood-brain barrier (BBB).
• To determine if FGF21 degradation occurs within the brain.
• To differentiate brain parenchymal entry from microvascular retention.

Main Methods:

• Multiple time-regression analysis to quantify BBB influx.
• Size-exclusion chromatography to assess FGF21 degradation.
• Capillary depletion technique to distinguish parenchymal entry.
• Efflux rate measurements to control for confounding factors.

Main Results:

• FGF21 influx rate across the BBB was determined to be 0.23 ± 0.12 µL/g/min.
• Approximately 70% of the FGF21 in brain tissue reached the parenchyma.
• FGF21 influx and efflux across the BBB were found to be non-saturable.
• FGF21 remained largely intact in both serum and brain tissue shortly after administration.

Conclusions:

• FGF21 exhibits significant, unidirectional, and non-saturable transport across the BBB.
• The findings support a direct role for FGF21 in brain function during fasting.
• Further research can explore therapeutic strategies targeting brain FGF21 levels.