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

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 PPARgamma receptor that stimulates adipocyte differentiation. We found this compound to be a potent stimulator of functional TSHR expression as well as TSHR and PPARgamma 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 PPARgamma receptor results in differentiation of these cells. It is possible that endogenous PPARgamma ligands play a role in stimulating orbital adipogenesis in GO, and that future treatments may be aimed at antagonism of various components of the PPARgamma signaling system.

Expression of thyrotropin and thyroid hormone receptors in adipose tissue of patients with morbid obesity and/or type 2 diabetes: effects of weight loss

“…Recent evidence in experimental animals and in humans has shown that adipocytes and preadipocytes possess TSH receptors (TSHRs), [11][12][13] and that TSH action induces the differentiation of preadipocytes into adipocytes, adipogenesis and, in children, lipolysis. 11,14,15 However, there are no data on the adipose tissue expression of the TSHR gene in conditions such as severe obesity and/or diabetes. Therefore this study was undertaken (1) to assess the separate role of obesity and type 2 diabetes (T2DM ) in the expression of the thyrotropin receptor (TSHR) and thyroid hormone receptor (a1 subunit, TRa1) genes in visceral adipose tissue (VAT) and in subcutaneous adipose tissue (SAT) and (2) to explore the role of metabolic state and weight loss on receptor expression.…”

Association between serum TSH concentration within the normal range and adiposity

“…However, 17 of the 29 reviewed studies found a positive association between anthropometric measures and serum TSH, and the two longitudinal population-based studies showed a positive association between serum TSH concentration and BMI or body weight (6,31). The plausibility of this association has been discussed and could be mediated by TSH action directly stimulating preadipocyte differentiation, thus inducing adipogenesis (36,37). Another hypothesis is that the association between serum TSH and body weight may be due to leptin (38).…”

Metabolic syndrome and its components are associated with increased thyroid volume and nodule prevalence in a mild-to-moderate iodine-deficient area

“…Animal and human studies have yielded convincing evidence that adipocytes and preadipocytes express TSH receptors (32). The action of TSH on its receptors in fat tissue induces differentiation of preadipocytes into adipocytes, causing stimulation of adipogenesis (33). All of these reciprocal mechanisms suggest that leptin and the thyroid axis maintain a complex and dual relationship and it might be proposed that a 'hypothalamic-pituitarythyroid-adipose axis' exists.…”