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GR C Baker, KJ Starkey, AE Heufelder, ME Ludgate; Adipogenesis in Thyroid Eye Disease Exacerbated by Thiazolidenedione Therapy: The Effect of PPAR Agonists and Antagonists on Preadipocyte Differentiation . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2414.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: A male patient treated with a thiazolidenedione (TZD) perioxisome proliferator activated receptor (PPAR)γ agonist for Type 2 diabetes had a dramatic worsening of his thyroid eye disease (TED), which had been stable and inactive for more then two years. Expansion of the orbital fat seemed to be the underlying cause and we have investigated the effects of a PPARγ agonist and an antagonist on the adipogenesis of preadipocytes from several fat depots, including TED orbits. Methods: The percentage of differentiating cells, assessed by oil red O staining, morphological changes and PPARγ transcript expression levels, was determined for preadipocytes in a hormone induced model of adipogenesis supplemented or not with PPARγ agonist or antagonist. Results: The PPARγ agonist resulted in a 2 to 10 fold increase and a PPARγ antagonist produced a 2 to 7 fold reduction in adipogenesis in the hormone induced model and are illustrated in the bar chart. The dotted line represents the level of differentiation under standard hormonal conditions and the samples are orbital(TED), cervical(CER), abdominal(ABD)and skin(HCA). The effects of the PPARγ agonist and antagonist were dose dependent and maximal at 10µ M but displayed no correlation with the fat depot analysed or the age/gender of the patient providing the sample. Conclusion: While PPARγ agonists may in other contexts have anti-inflammatory properties, in TED the reactivation of orbital adipogenesis in this patient leads us to recommend close supervision of any patient with a history of Graves' disease or TED that is treated with a PPARγ agonist. Our work also suggests that PPARγ antagonists could provide a novel therapeutic intervention to reduce orbital fat volume expansion in active TED.
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