Systemic fate of the adipocyte-derived factor adiponectin

Nils Halberg, Todd D. Schraw, Zhao V. Wang, Ja Young Kim, James Yi, Mark P. Hamilton, Kate Luby-Phelps, Philipp E. Scherer

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1961-1970
Number of pages10
JournalDiabetes
Volume58
Issue number9
DOIs
StatePublished - Sep 2009

Fingerprint

Adiponectin
Adipocytes
Half-Life
High Fat Diet
Cysteine
Adipose Tissue
Hepatocytes
Anti-Inflammatory Agents
Research Design
Insulin
Mutation
Liver

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Halberg, N., Schraw, T. D., Wang, Z. V., Kim, J. Y., Yi, J., Hamilton, M. P., ... Scherer, P. E. (2009). Systemic fate of the adipocyte-derived factor adiponectin. Diabetes, 58(9), 1961-1970. https://doi.org/10.2337/db08-1750

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.

In: Diabetes, Vol. 58, No. 9, 09.2009, p. 1961-1970.

Research output: Contribution to journalArticle

Halberg, N, Schraw, TD, Wang, ZV, Kim, JY, Yi, J, Hamilton, MP, Luby-Phelps, K & Scherer, PE 2009, 'Systemic fate of the adipocyte-derived factor adiponectin', Diabetes, vol. 58, no. 9, pp. 1961-1970. https://doi.org/10.2337/db08-1750
Halberg N, Schraw TD, Wang ZV, Kim JY, Yi J, Hamilton MP et al. Systemic fate of the adipocyte-derived factor adiponectin. Diabetes. 2009 Sep;58(9):1961-1970. https://doi.org/10.2337/db08-1750
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. In: Diabetes. 2009 ; Vol. 58, No. 9. pp. 1961-1970.
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