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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. RESEARCH DESIGN AN...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731534/ https://www.ncbi.nlm.nih.gov/pubmed/19581422 http://dx.doi.org/10.2337/db08-1750 |
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author | Halberg, Nils Schraw, Todd D. Wang, Zhao V. Kim, Ja-Young Yi, James Hamilton, Mark P. Luby-Phelps, Kate Scherer, Philipp E. |
author_facet | Halberg, Nils Schraw, Todd D. Wang, Zhao V. Kim, Ja-Young Yi, James Hamilton, Mark P. Luby-Phelps, Kate Scherer, Philipp E. |
author_sort | Halberg, Nils |
collection | PubMed |
description | 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. RESEARCH DESIGN AND 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 ∼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. |
format | Text |
id | pubmed-2731534 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-27315342010-09-01 Systemic Fate of the Adipocyte-Derived Factor Adiponectin Halberg, Nils Schraw, Todd D. Wang, Zhao V. Kim, Ja-Young Yi, James Hamilton, Mark P. Luby-Phelps, Kate Scherer, Philipp E. Diabetes Original Article 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. RESEARCH DESIGN AND 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 ∼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. American Diabetes Association 2009-09 2009-07-06 /pmc/articles/PMC2731534/ /pubmed/19581422 http://dx.doi.org/10.2337/db08-1750 Text en © 2009 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Original Article Halberg, Nils Schraw, Todd D. Wang, Zhao V. Kim, Ja-Young Yi, James Hamilton, Mark P. Luby-Phelps, Kate Scherer, Philipp E. Systemic Fate of the Adipocyte-Derived Factor Adiponectin |
title | Systemic Fate of the Adipocyte-Derived Factor Adiponectin |
title_full | Systemic Fate of the Adipocyte-Derived Factor Adiponectin |
title_fullStr | Systemic Fate of the Adipocyte-Derived Factor Adiponectin |
title_full_unstemmed | Systemic Fate of the Adipocyte-Derived Factor Adiponectin |
title_short | Systemic Fate of the Adipocyte-Derived Factor Adiponectin |
title_sort | systemic fate of the adipocyte-derived factor adiponectin |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731534/ https://www.ncbi.nlm.nih.gov/pubmed/19581422 http://dx.doi.org/10.2337/db08-1750 |
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