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Evidence for Enhanced Adipogenesis in the Orbits of Patients with Graves’ Ophthalmopathy

Divisions of Pediatric Endocrinology (S.K.) and Endocrinology, Metabolism, and Nutrition (M.J.C., R.S.B.), Mayo Clinic, Rochester, Minnesota 55905; and Department of Cell Biology and Diabetes Research and Training Center, Albert Einstein College of Medicine (P.E.S.), Bronx, New York 10461

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

The signs and symptoms of Graves’ ophthalmopathy (GO) result from increased volume of the orbital contents, including adipose, connective, and extraocular muscle tissues. We wanted to determine whether the expanded adipose tissue volume might be in part attributable to de novo adipogenesis. We measured levels of mRNA encoding leptin, adiponectin, peroxisome proliferator-activated receptor (PPAR), preadipocyte factor-1, and TSH receptor (TSHr) genes in orbital adipose tissues from GO patients (n = 22) and normal individuals (n = 18) and in orbital preadipocyte cultures derived from GO patients (n = 6) and normal subjects (n = 3) using quantitative real-time RT PCR. We found increased leptin, adiponectin, PPAR, and TSHr expression in GO compared with normal orbital tissue samples, with positive correlations in the GO tissues between TSHr and leptin, adiponectin and PPAR. In vitro differentiation of GO and normal preadipocytes resulted in enhanced adiponectin, leptin, and TSHr expression, with greater expression of the latter two genes in the GO cultures. These results suggest that de novo adipogenesis within orbital tissues with parallel enhanced expression of TSHr may be important in the pathogenesis of GO, and that potential therapies for GO might include inhibition of the adipogenic pathway.

This work was supported in part by NIH Grant EYO8819 (to R.S.B.) from the National Eye Institute.

Abbreviations: FBS, Fetal bovine serum; GO, Graves’ ophthalmopathy; PPAR, peroxisome proliferator-activated receptor ; pref-1, preadipocyte factor-1; rRNA, ribosomal RNA; TSHr, TSH receptor.

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