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Endocrine Abstracts (2005) 9 OC39

BES2005 Oral Communications Oral Communication 5: Thyroid (7 abstracts)

Thyrotropin receptor (TSHR) activation in preadipocytes stimulates the early but inhibits the terminal stages of adipogenesis

D Janus 1 , GRC Baker 1 , D Fuhrer 2 & M Ludgate 1

1Centre for Endocrine & Diabetes Sciences, Cardiff University, Cardiff, UK; 2Medizinische Klinik III, University of Leipzig, Leipzig, Germany.

The TSHR is expressed during adipogenesis. We have employed in vitro models to investigate how TSHR activation affects this process. Gain-of-function TSHR mutants were introduced into preadipocytes using retroviral vectors. We have demonstrated that TSHR activation inhibits their proliferation and PPAR-gamma agonist (pioglitazone) induced adipogenesis. The aim of this study was to investigate the mechanisms operating.

Non-modified primary human preadipocytes (n=3) or the same line expressing M453T, L629F or WT TSHR were maintained in low serum medium (LSM) or in a differentiation protocol (DIFF) including 1uM pioglitazone. Oil red O staining lipids were quantified by measuring the OD490. The values in LSM or DIFF-LSM provide measures of basal and induced adipogenesis respectively. Transcripts for early, intermediate and late markers of adipogenesis were quantified using SYBR green and a light cycler.

Basal lipid levels were significantly increased in the mutant (127 to 275%) compared with non-modified (100%) or WT (104 to 187%) expressing cells. This was accompanied by fold increases in C/EBP-beta (2 to 10, early); PPAR-gamma (2 to 4, intermediate) and UCP-1 transcripts (2 to 8, marker of BAT). Lipoprotein lipase transcripts (LPL, late) were at the limit of detection.

In the DIFF protocol, induced lipid levels were mostly reduced by expression of the mutant TSHR (16 to 33% of non-modified, 100%). Adipogenesis in the non-modified lines was associated with 1.5 to 5 (C/EBP-beta); 7 to 20 (PPAR-gamma), 10 to 150 (UCP-1) and 20 to 30 (LPL) fold increases (relative to LSM). This compares with a reduction, 0 to 4, 0 to 7 and 0 fold increases respectively in the mutant TSHR expressing cells.

In conclusion, TSHR activation stimulates early differentiation (favouring development of BAT?) but renders preadipocytes refractory to PPAR-gamma induced adipogenesis. In neither case do lipid-containing vacuoles accumulate suggesting that terminal stages of differentiation have been inhibited.

Volume 9

24th Joint Meeting of the British Endocrine Societies

British Endocrine Societies 

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