Plasma adiponectin complexes have distinct biochemical characteristics

Todd Schraw, Zhao V. Wang, Nils Halberg, Meredith Hawkins, Philipp E. Scherer

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

Adipocytes release the secretory protein adiponectin in a number of different higher-order complexes. Once synthesized and assembled in the secretory pathway of the adipocyte, these complexes circulate as biochemically distinct and stable entities with little evidence of interchange between the different forms that include a high-molecular-weight (HMW) species, a hexamer (low-molecular-weight form), and a trimeric form of the complexes. Here, we validate a high-resolution gel filtration method that reproducibly separates the three complexes in recombinant adiponectin and adiponectin from human and murine samples. We demonstrate that the HMW form is prominently reduced in male vs. female subjects and in obese, insulin-resistant vs. lean, insulin-sensitive individuals. A direct comparison of human and mouse adiponectin demonstrates that the trimer is generally more abundant in human serum. Furthermore, when the production of adiponectin is reduced, either by obesity or in mice carrying only a single functional allele of the adiponectin locus, then the amount of the HMW form is selectively reduced in circulation. The complex distribution of adiponectin can be regulated in several ways. Both mouse and human HMW adiponectin are very stable under basic conditions but are exquisitely labile under acidic conditions below pH 7. Murine and human adiponectin HMW forms also display differential susceptibility to the presence of calcium in the buffer. A mutant form of adiponectin unable to bind calcium is less susceptible to changes in calcium concentrations. However, the lack of calcium binding results in a destabilization of the structure. Disulfide bond formation (at position C39) is also important for complex formation. A mutant form of adiponectin lacking C39 prominently forms HMW and trimer but not the low-molecular-weight form. Injection of adiponectin with a fluorescent label reveals that over time, the various complexes do not interconvert in vivo. The stability of adiponectin complexes highlights that the production and secretion of these forms from fat cells has a major influence on the circulating levels of each complex.

Original languageEnglish (US)
Pages (from-to)2270-2282
Number of pages13
JournalEndocrinology
Volume149
Issue number5
DOIs
StatePublished - May 2008

Fingerprint

Adiponectin
Molecular Weight
Adipocytes
Calcium
Insulin
Secretory Pathway
Disulfides
Gel Chromatography
Buffers
Obesity
Alleles
Injections

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Plasma adiponectin complexes have distinct biochemical characteristics. / Schraw, Todd; Wang, Zhao V.; Halberg, Nils; Hawkins, Meredith; Scherer, Philipp E.

In: Endocrinology, Vol. 149, No. 5, 05.2008, p. 2270-2282.

Research output: Contribution to journalArticle

Schraw, Todd ; Wang, Zhao V. ; Halberg, Nils ; Hawkins, Meredith ; Scherer, Philipp E. / Plasma adiponectin complexes have distinct biochemical characteristics. In: Endocrinology. 2008 ; Vol. 149, No. 5. pp. 2270-2282.
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