Biological effects of thyrotropin receptor activation on human orbital dreadipocytes

Zhang, Lei ORCID: https://orcid.org/0000-0003-3536-8692, Baker, Glynn, Janus, Dominika, Paddon, Carol A., Fuhrer, Dagmar and Ludgate, Marian 2006. Biological effects of thyrotropin receptor activation on human orbital dreadipocytes. Investigative Ophthalmology & Visual Science 47 (12) , pp. 5197-5203. 10.1167/iovs.06-0596

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Abstract

purpose. Thyrotropin receptor (TSHR) expression is upregulated in the orbits of patients with Graves ophthalmopathy (GO), most of whom have TSHR-stimulating antibodies. The authors investigated the biological effects of TSHR activation in vitro in adipose tissue, the site of orbital TSHR expression. methods. Activating mutant TSHR (TSHR*) or wild-type (WT) was introduced into human orbital preadipocytes using retroviral vectors. Their proliferation (Coulter counting), basal cAMP accumulation (radioimmunoassay), and spontaneous and peroxisome proliferator-activated receptor (PPARγ)-induced adipogenesis (quantitative oil red O staining) were assessed and compared with those of nonmodified cells. QRT-PCR was used to measure transcripts of CCAT/enhancer binding protein (C/EBP)β, PPARγ, and lipoprotein lipase (LPL; early, intermediate, and late markers of adipogenesis) and for uncoupling protein (UCP)-1 (brown adipose tissue [BAT]). results. Expression of TSHR* significantly inhibited the proliferation of preadipocytes and produced an increase in unstimulated cAMP of 200% to 600%. Basal lipid levels were significantly increased in TSHR* (127%–275%) compared with nonmodified (100%) or WT-expressing (104%–187%) cells. This was accompanied by 2- to 10-fold increases in early-intermediate markers and UCP-1 transcripts (2- to 8-fold); LPL was at the limit of detection. In nonmodified cells, adipogenesis produced significant increases in transcripts of all markers, including LPL (approximately 30-fold). This was not the case in TSHR*-expressing cells, which also displayed 67% to 84% reductions in lipid levels. conclusions. TSHR activation stimulates early differentiation (favoring BAT formation?) but renders preadipocytes refractory to PPARγ-induced adipogenesis. In neither case did lipid-containing vacuoles accumulate, suggesting that terminal stages of differentiation were inhibited.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Association for Research in Vision and Ophthalmology
ISSN:	1552-5783
Date of First Compliant Deposit:	27 June 2017
Last Modified:	05 May 2023 18:52
URI:	https://orca.cardiff.ac.uk/id/eprint/101772

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