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Thalidomide inhibits adipogenesis of orbital fibroblasts in Graves’ ophthalmopathy

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Abstract

The expansion of orbital adipose tissue is a main pathophysiology of Graves’ ophthalmopathy (GO), which is an inflammatory autoimmune disease in the orbital region. The effects of immunosuppressive drugs on adipogenesis of orbital fibroblasts have not been determined. Thalidomide, as an immunosuppressive drug, has recently been used in the therapy of many autoimmune diseases. In this study, we analyzed the effects of thalidomide on adipogenesis and found that adipocyte differentiation from preadipocytes in the orbital region was enhanced, which was demonstrated by enhanced expression of peroxisome proliferator activated receptor γ (PPARγ), ap2, and thyroid-stimulating hormone receptor (TSHR). The expression of inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin 6 (IL-6) was also increased in GO. Thalidomide dose-dependently inhibited adipogenesis of 3T3-L1 preadipocytes and orbital fibroblasts from GO patients. Along with the inhibited adipogenesis, the expression of TSHR, TNFα, and IL-6 was also down-regulated. We discovered that the mechanism for thalidomide inhibiting adipogenesis was the down-regulation of PPARγ, rather than C/EBPβ and C/EBPδ. We suggest that, besides its canonical anti-TNFα effect, thalidomide plays a role in inhibiting adipogenesis of orbital fibroblasts in GO patients.

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Abbreviations

GO:

Graves’ ophthalmopathy

TAO:

Thyroid-associated ophthalmopathy

TSHR:

Thyroid-stimulating hormone receptor

TNFα:

Tumor necrosis factor α

IL-6:

Interleukin 6

PPARγ:

Peroxisome proliferator activated receptor γ

ap2:

Adipocyte protein 2

C/EBPβ:

CCAAT enhancer binding protein β

C/EBPδ:

CCAAT enhancer binding protein δ

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Acknowledgment

The authors are grateful to Dr. Tan for providing orbital tissue and for the patients who took part in the study. This study was supported by a grant from the medical science research project of Zhejiang province (2007B174).

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Hangzhou First People’s Hospital, Nanjing Medical University, Xueshi Road 4#, Hangzhou City, 310006, Zhejiang Province, China

    Chu Zhang, Xianfeng Zhang, Lizhen Ma, Fengying Peng, Jiao Huang & Hui Han

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  1. Chu Zhang
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  2. Xianfeng Zhang
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Correspondence to Xianfeng Zhang.

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Zhang, C., Zhang, X., Ma, L. et al. Thalidomide inhibits adipogenesis of orbital fibroblasts in Graves’ ophthalmopathy. Endocrine 41, 248–255 (2012). https://doi.org/10.1007/s12020-012-9600-8

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  • DOI: https://doi.org/10.1007/s12020-012-9600-8

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