The Fasting Polypeptide FGF21 Can Enter Brain From Blood

Peptides. 2007 Dec;28(12):2382-6. doi: 10.1016/j.peptides.2007.10.007. Epub 2007 Oct 18.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biological Transport, Active
  • Blood-Brain Barrier / physiology*
  • Brain / metabolism
  • Fasting / blood*
  • Fasting / metabolism*
  • Fibroblast Growth Factors / administration & dosage
  • Fibroblast Growth Factors / blood*
  • Fibroblast Growth Factors / metabolism*
  • Humans
  • Kinetics
  • Liver / metabolism
  • Male
  • Muscle, Skeletal / metabolism
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / blood
  • Recombinant Proteins / metabolism

Substances

  • Recombinant Proteins
  • fibroblast growth factor 21
  • Fibroblast Growth Factors