Selective Tissue Uptake of Agouti-Related Protein(82–131) and Its Modulation by Fasting

Selective Tissue Uptake of Agouti-Related Protein(82–131) and Its Modulation by Fasting

The blood concentration of agouti-related protein (AgRP), a protein related to hyperphagia and obesity, is increased in obese human and fasted lean subjects. Because there is no saturable transport system at the blood-brain barrier for circulating AgRP to reach its central nervous system target, upt...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) Vol. 146; no. 12; pp. 5533 - 5539
Main Authors: Pan, Weihong, Kastin, Abba J, Yu, Yongmei, Cain, Courtney M, Fairburn, Tammy, Stütz, Adrian M, Morrison, Christopher, Argyropoulos, George
Format: Journal Article
Language:English
Published: Bethesda, MD Endocrine Society 01-12-2005
Oxford University Press
Subjects:
Adipose Tissue - metabolism
Adrenal glands
Adrenal Glands - metabolism
Agouti-Related Protein
Albumins - pharmacokinetics
Animals
Biological activity
Biological and medical sciences
Blood circulation
Blood flow
Blood levels
Blood-brain barrier
Brain - metabolism
Central nervous system
Dietary restrictions
Drug Stability
Epididymis
Fasting
Fasting - metabolism
Food processing
Fundamental and applied biological sciences. Psychology
Hyperphagia
Injection
Injections, Intravenous
Liver
Liver - metabolism
Male
Mice
Mice, Inbred C57BL
Obesity
Organs
Peptide Fragments - administration & dosage
Peptide Fragments - chemistry
Peptide Fragments - pharmacokinetics
Permeability
Pharmacokinetics
Protein transport
Proteins
Radioactivity
Skeletal muscle
Spinal cord
Time Factors
Tissue Distribution
Transportation systems
Vertebrates: endocrinology
Fasting
AGOUTI related protein
Modulation
Uptake
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Summary:The blood concentration of agouti-related protein (AgRP), a protein related to hyperphagia and obesity, is increased in obese human and fasted lean subjects. Because there is no saturable transport system at the blood-brain barrier for circulating AgRP to reach its central nervous system target, uptake of AgRP by peripheral organs might be physiologically meaningful. Using the biologically active fragment AgRP(82–131), we determined the pharmacokinetics of its radioactively labeled tracer after iv bolus injection and compared it with that of the vascular marker albumin. AgRP enters peripheral organs at different influx rates, all of which were higher than into brain and spinal cord. At 10 min after iv injection, the radioactivity recovered in the liver, which had the fastest influx rate for AgRP, represented intact 125I-AgRP. The adrenal gland had a moderately fast uptake (but the highest initial volume of distribution), followed by the heart, lungs, and skeletal muscle. By comparison, epididymal fat, testis, and pancreas had low permeability to AgRP. Saturation of influx was determined by coadministration of excess unlabeled AgRP and was shown to be present in the liver and adrenal gland. The influx rate and initial volume of distribution did not show a linear correlation with vascular permeability or regional blood flow. AgRP uptake by the liver and epididymal fat was significantly increased by overnight fasting, whereas that by the adrenal gland was significantly decreased in fasted mice. Thus, the differential uptake of AgRP by peripheral organs could be a regulated process that is modulated by food deprivation.
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ISSN:0013-7227
1945-7170
DOI:10.1210/en.2005-0578