Systemic fate of the adipocyte-derived factor adiponectin.
OBJECTIVE
The adipocyte-derived secretory protein adiponectin has been widely studied and shown to have potent insulin-sensitizing, antiapoptotic, and anti-inflammatory properties. While its biosynthesis is well understood, its fate, once in circulation, is less well established.


METHODS
Here, we examine the half-life of adiponectin in circulation by tracking fluorescently labeled recombinant adiponectin in the circulation, following it to its final destination in the hepatocyte.


RESULTS
Despite its abundant presence in plasma, adiponectin is cleared rapidly with a half-life of approximately 75 min. A more bioactive version carrying a mutation at cysteine 39 is cleared within minutes. Even though steady-state levels of adiponectin differ between male and female mice, we failed to detect any differences in clearance rates, suggesting that differences in plasma are mostly due to differential production rates. In a metabolically challenged state (high-fat diet exposure or in an ob/ob background), adiponectin levels are reduced in plasma and clearance is significantly prolonged, reflecting a dramatic drop in adiponectin production levels.


CONCLUSIONS
Combined, these results show a surprisingly rapid turnover of adiponectin with multiple fat pads contributing to the plasma levels of adiponectin and clearance mediated primarily by the liver. It is surprising that despite high-level production and rapid clearance, plasma levels of adiponectin remain remarkably constant.
Halberg
Nils
N
Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Schraw
Todd D
TD
Wang
Zhao V
ZV
Kim
Ja-Young
JY
Yi
James
J
Hamilton
Mark P
MP
Luby-Phelps
Kate
K
Scherer
Philipp E
PE
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D052242:Adiponectin / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology; D005260:Female; D005456:Fluorescent Dyes; D022781:Hepatocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D011247:Pregnancy; D011994:Recombinant Proteins / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D012727:Sex Characteristics; D015398:Signal Transduction / Q000502:physiology
D052242:Adiponectin; C499919:Adipoq protein, mouse; D001786:Blood Glucose; D004041:Dietary Fats; D005456:Fluorescent Dyes; D011994:Recombinant Proteins