The multimerization and secretion of adiponectin are regulated by TNF-alpha
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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.
KeywordsObesity Adiponectin Multimerization Secretion PPARγ
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).
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Conflict of interest
The authors declare that they have no conflict of interest regarding this article.
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