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Stimulation of Adipogenesis, Peroxisome Proliferator-Activated Receptor- (PPAR), and Thyrotropin Receptor by PPAR Agonist in Human Orbital Preadipocyte Fibroblasts

Division of Endocrinology, Metabolism, and Nutrition, Mayo Clinic/Foundation, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Rebecca S. Bahn, M.D., Division of Endocrinology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905. E-mail: . bahn.rebecca{at}mayo.edu

Abstract

The symptoms and signs of Graves’ ophthalmopathy (GO) result from both an accumulation of hydrated hyaluronan in the orbital muscles and connective tissues and an expansion of the orbital adipose tissues. Recent studies have suggested a link between the stimulation of adipogenesis within the orbit in GO and the expression in these tissues of TSH receptor (TSHR), the putative orbital autoantigen. To further investigate this association, we treated orbital fibroblasts from patients with GO with rosiglitazone, a thiazolidinedione agonist of the PPAR receptor that stimulates adipocyte differentiation. We found this compound to be a potent stimulator of functional TSHR expression as well as TSHR and PPAR mRNA levels in differentiated cultures. In addition, rosiglitazone treatment stimulated recruitment and differentiation of a subset of cells within these cultures into mature lipid-laden adipocytes.

These results suggest that TSHR expression in GO orbital preadipocyte fibroblasts is linked to adipogenesis, and that ligation of the PPAR receptor results in differentiation of these cells. It is possible that endogenous PPAR ligands play a role in stimulating orbital adipogenesis in GO, and that future treatments may be aimed at antagonism of various components of the PPAR signaling system.

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