title: Thalidomide inhibits adipogenesis of orbital fibroblasts in Graves' ophthalmopathy.
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.
authors.affiliation: Department of Endocrinology and Metabolism, Hangzhou First People's Hospital, Nanjing Medical University, Xueshi Road 4#, Hangzhou City, 310006 Zhejiang Province, China.
authors.forename: Chu
authors.initials: C
authors.lastname: Zhang
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Zhang
authors.forename: Lizhen
authors.initials: L
authors.lastname: Ma
authors.forename: Fengying
authors.initials: F
authors.lastname: Peng
authors.forename: Jiao
authors.initials: J
authors.lastname: Huang
authors.forename: Hui
authors.initials: H
authors.lastname: Han
mesh_terms: D041721:3T3-L1 Cells; D052438:Adipocytes, White / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D049970:Graves Ophthalmopathy / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009915:Orbit; D009994:Osmolar Concentration; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000378:metabolism; D013792:Thalidomide / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; C508600:IL6 protein, human; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D047495:PPAR gamma; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide