The Role of Thyrotropin Receptor Activation in Adipogenesis and Modulation of Fat Phenotype

Evidence from clinical and experimental data suggests that thyrotropin receptor (TSHR) signaling is involved in energy expenditure through its impact on white adipose tissue (WAT) and brown adipose tissue (BAT). TSHR expression increases during mesenchymal stem cell (MSC) differentiation into fat. W...

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Published in:Frontiers in endocrinology (Lausanne) 2017-04, Vol.8, p.83-83
Main Authors: Draman, Mohd Shazli, Stechman, Michael, Scott-Coombes, David, Dayan, Colin M, Rees, Dafydd Aled, Ludgate, Marian, Zhang, Lei
Format: Article
Language:eng
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Summary:Evidence from clinical and experimental data suggests that thyrotropin receptor (TSHR) signaling is involved in energy expenditure through its impact on white adipose tissue (WAT) and brown adipose tissue (BAT). TSHR expression increases during mesenchymal stem cell (MSC) differentiation into fat. We hypothesize that TSHR activation [TSHR*, elevated thyroid-stimulating hormone, thyroid-stimulating antibodies (TSAB), or activating mutation] influences MSC differentiation, which contributes to body composition changes seen in hypothyroidism or Graves' disease (GD). The role of TSHR activation on adipogenesis was first investigated using samples. Neck fat (all euthyroid at surgery) was obtained from GD (  = 11, TSAB positive), toxic multinodular goiter (TMNG, TSAB negative) (  = 6), and control patients with benign euthyroid disease (  = 11, TSAB negative). The effect of TSHR activation was then analyzed using human primary abdominal subcutaneous preadipocytes (  = 16). Cells were cultured in complete medium (CM) or adipogenic medium [ADM, containing thiazolidinedione (TZD), PPARγ agonist, which is able to induce BAT formation] with or without TSHR activation (gain-of-function mutant) for 3 weeks. Adipogenesis was evaluated using oil red O (ORO), counting adipogenic foci, qPCR measurement of terminal differentiation marker ( ). BAT [ , uncoupling protein 1 ( ), and ], pre-BAT ( ), BRITE- ( ), or WAT ( ) markers were analyzed by semiquantitative PCR or qPCR. In analysis, there were no differences in the expression of , and . BRITE marker levels were highest in GD followed by TMNG and control ( for trend = 0.009). This was associated with higher WAT marker level in GD than the other two groups (  
ISSN:1664-2392
1664-2392