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Endocrine

, Volume 51, Issue 3, pp 456–468 | Cite as

The multimerization and secretion of adiponectin are regulated by TNF-alpha

  • Yiduo He
  • Linfang Lu
  • Xuan Wei
  • Dan Jin
  • Tao Qian
  • An Yu
  • Jun Sun
  • Jiesheng Cui
  • Zaiqing YangEmail author
Original Article

Abstract

Obesity is often associated with insulin resistance, mild systemic inflammation, and decreased blood adiponectin. However, some adipokines are increased in the adipose tissue of obese individuals, and whether these adipokines are directly related to the reductions in serum adiponectin levels in an autocrine or paracrine manner remains unknown. This study indicates that the tumor necrosis factor alpha (TNF-α) suppresses the multimerization and secretion of adiponectin both in vitro and in vivo. Additionally, TNF-α remarkably suppressed the expression of the ER-resident chaperone proteins ERO1-La, DsbA-L, and ERp44. Overexpression of the transcription factor PPARγ antagonized the suppressive effect of TNF-α on ERO1-La and DsbA-L expressions. Further study revealed that PPARγ enhanced the transcription of ERO1-La and DsbA-L by directly binding to the PPRE element of ERO1-La and DsbA-L promoters. TNF-α treatment decreased this binding activity. Furthermore, TNF-α treatment enhanced the interaction between adiponectin and ERp44. In this study, we show that TNF-α impairs adiponectin multimerization and consequently decreases adiponectin secretion by altering disulfide bond modification in the endoplasmic reticulum. Altered adiponectin multimerization could explain declined adiponectin levels and altered distribution of adiponectin complexes in the plasma of obese insulin-resistant individuals.

Keywords

Obesity Adiponectin Multimerization Secretion PPARγ 

Notes

Acknowledgments

This work was supported by the grants from the National key Basic Research Program of China (2012CB124702), 948 Program (2012-S13, 2013-S15), Specialized Research Fund for the Doctoral Program of Higher Education (20110146130002), Program of National Natural Science Foundation of China (31172093), the National Science Foundation for Fostering Talents in Basic Research (J1103510), and the Fundamental Research Funds for the Central Universities (2013PY005).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest regarding this article.

Supplementary material

12020_2015_741_MOESM1_ESM.tif (768 kb)
Supplementary data-Fig. s1 TNF-alpha suppresses protein level of ERO1-La and DsbA-L in a dose- and time-dependent manner. The cells were lysed and subjected to Western blot to dose–response and time-course analysis of ERO1-La, DsbA-L, PPARγ, and actin protein content in adipocytes, the densitometric analysis of Western blot was made to compare the relative protein level of (a) ERO1-La, (b) DsbA-L and (c) PPARγ under the dose–response and time-course treatment of TNF-alpha. The results are presented as the mean ± SEM of three independent experiments. *p < 0.05; **p < 0.01; ***p < 0.001 Supplementary material 1 (TIFF 767 kb)

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Yiduo He
    • 1
  • Linfang Lu
    • 1
  • Xuan Wei
    • 1
  • Dan Jin
    • 1
  • Tao Qian
    • 1
  • An Yu
    • 1
  • Jun Sun
    • 1
  • Jiesheng Cui
    • 1
  • Zaiqing Yang
    • 1
    Email author
  1. 1.Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and TechnologyHuazhong Agricultural UniversityWuhanPeople’s Republic of China

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