The fasting polypeptide FGF21 can enter brain from blood.
FGF21 recently has been proposed as a missing link in the biology of fasting, raising the question of whether it directly reaches the brain. We used multiple time-regression analysis to quantify the influx rate of this polypeptide across the blood-brain barrier (BBB), size-exclusion chromatography to examine degradation, capillary depletion to differentiate entry into brain parenchyma from retention in the microvasculature, and measurement of efflux rate to determine a possible confounding effect on measurement of entry. FGF21 was 94% intact in serum and 75% in brain 10 min after intravenous bolus delivery. Its influx rate was 0.23+/-0.12 microl/g-min, nearly four times faster than that of the vascular marker albumin. At 10 min, about 0.5% of the administered FGF21 was present in a gram of brain tissue. Of this, 70% reached the parenchyma of the brain. Co-injection of excess FGF21 failed to inhibit the influx, showing a lack of saturation. Efflux, which occurred at the same rate as the bulk reabsorption of cerebrospinal fluid, also was not saturable. In summary, FGF21 shows significant, non-saturable, unidirectional influx across the BBB.
Hsuchou
Hung
H
Blood-Brain Barrier Group, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
Pan
Weihong
W
Kastin
Abba J
AJ
D000818:Animals; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D005215:Fasting / Q000097:blood* / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism
D011994:Recombinant Proteins; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors