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

Abstract

Objective: Increased thyroid-stimulating hormone (TSH) and FT 3 levels are often found in clinically euthyroid obese individuals. Information on thyroid gene expression in human adipose tissue is scarce. The objective of this study was to measure the expression of the TSH receptor (TSHR) and the thyroid hormone receptor (TRa1) genes in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in obese individuals and to test the effect of weight loss on these genes. Study Design and Participants: This study is a prospective study involving 107 obese (body mass index (BMI) ¼ 46±8 kg m À2 , 52 with type 2 diabetes or impaired glucose tolerance) and 12 lean nondiabetic participants. A total of 27 obese patients were restudied 1 year after gastric bypass surgery. Total RNA was extracted from SAT and VAT obtained at baseline from all participants, and from SAT in obese patients post surgery. Results: Circulating TSH and FT 3 levels were 170 and 36%, respectively, higher in obese patients than in controls. In SAT, TSHR and TRa1 were reduced in the obese by 67 and 33%, respectively, regardless of glucose tolerance. A similar trend was found in VAT. Post surgery, a BMI decrease of 33% was associated with a decrease in TSH and FT 3 levels and with a 150 and 70% increase in SAT of TSHR and TRa1, respectively. Conclusion: In both subcutaneous and visceral fat, the thyroid gene expression (especially TSHR) is reduced in obesity. The reversal of these changes with major weight loss and the reciprocal changes in plasma TSH and FT 3 levels suggest a role for adipocytes in the regulation of TSH and thyroid hormones.

The prevalence of the metabolic syndrome increases through the quartiles of thyroid stimulating hormone in a population-based sample of euthyroid subjects

“…On the one hand thyroid hormones and TSH alter the metabolic activity of the fat tissue (24). On the other hand a relative thyroid hormone resistant state in obesity has been proposed by some authors (25). Most probably there is a complex interplay between various mechanisms, as demonstrated by the observations of Muscogiuri and cols.…”

Obesity and thyroid cancer

“…A negative association between BMI and serum free thyroxine (T 4 ) levels was reported (Knudsen et al 2005), with lower T 4 levels being associated with fat accumulation (Knudsen et al 2005, Alevizaki et al 2009. A moderate increase in triiodothyronine (T 3 ) levels observed in obese subjects (Reinehr et al 2006, De Pergola et al 2007, Nannipieri et al 2009) has been explained by a higher conversion of T 4 to T 3 as a compensatory mechanism for fat accumulation to improve energy expenditure (De Pergola et al 2007). Positive associations were also observed between free T 3 level and both waist circumference and BMI in obese patients (De Pergola et al 2007).…”

Stimulation of Thermogenesis via Beta-Adrenergic and Thyroid Hormone Receptors Agonists in obesity Treatment – Possible Reasons for Therapy Resistance

“…The isoforms have tissue-and organ specific localisation, with TRα1 being a predominant isoform in the brain, bone, heart and intestine, TRα2 -a variant receptor that lacks a functional hormone-binding site and antagonizes TRα1 action, TRβ1 dominating in liver, kidney and thyroid and TRβ2 being a chief form involved in the regulation of the hypothalamus-pituitary axis and in the neurosensory development [51]. Both TRα1 and TRβ1 are also expressed in human adipose tissue [50,52] and there is data coming from the observational, animal and genetic studies suggesting that they could constitute potential targets for obesity treatment.…”

“…This phenomenon can be partially explained by the differences in the TRs expression between the visceral and subcutaneous tissues as well as between obese and slim individuals [50]. The decreased expression of TRs in adipose tissues of obese individuals is also suggested as a potential mechanism of a relative resistance to thyroid hormone that manifests itself by the increased fT3 serum levels [52] and correlates positively with the increase in weight [55]. Another explanation for the elevation of fT3 (and thyroid stimulating hormone -TSH) in obese individuals is the regulatory action of leptin -an adipokine secreted by the adipose tissue that can promote expression of the thyreotropin releasing hormone (TRH) gene in the hypothalamus and increase peripheral conversion of T4 to T3 via stimulation of deiodinases.…”

“…New TRα selective agonists are being studied in order to improve our understanding of the role of this isoform in termogenesis and other T3 regulated processes [74]. The effectiveness of these compounds, however, may be limited due to the decreased expression of THRA and THRB genes in adipose tissues of obese individuals [50,52].…”