The fasting polypeptide FGF21 can enter brain from blood
Open accessAbstract
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.
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FGF21 crosses the blood-brain barrier and acts centrally to regulate multiple processes.
“FGF21 crosses the blood–brain barrier and acts centrally to regulate multiple processes (50).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [50]
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- Authors
- Hsuchou, H., Pan, W., & Kastin, A. J.
- Affiliations
- Pennington Biomedical Research Center (US)
- Corresponding author
- Pan, Weihong
- ORCID
- Pan, Weihong
- Venue
- Peptides
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 28
- Issue
- 12
- Pages
- 2382-2386
- ISSN
- 0196-9781 (ISSN-L)
- PMC
- PMC2151924
- OpenAlex
- W2054119106
- Cited by
- 280
- References
- 20
- Citations by year
- 2026: 16 · 2025: 31 · 2024: 25 · 2023: 21 · 2022: 25 · 2021: 19 · 2020: 18 · 2019: 24 · 2018: 14 · 2017: 20 · 2016: 10 · 2015: 12 · 2014: 12 · 2013: 7 · 2012: 10
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Peptides (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-54880, R01DK054880, R56DK054880)
- National Institute of Neurological Disorders and Stroke (R01NS046528, R01NS045751, NS45751, NS-46528)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- FGF21, fasting, blood-brain barrier, brain uptake, albumin, efflux, cerebrospinal fluid reabsorption, brain parenchyma
- MeSH terms
- Animals, Biological Transport, Active, Blood-Brain Barrier, Brain, Fasting, Fibroblast Growth Factors, Humans, Kinetics, Liver, Male, Recombinant Proteins, Muscle, Skeletal
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