Circulating Concentrations of GDF11 are Positively Associated with TSH Levels in Humans.

Juan Añón-Hidalgo,Victoria Catalán,Beatriz Ramírez,Carmen Mugueta,Javier Gómez-Ambrosi,Adrián Idoate-Bayón,Gema Frühbeck,Juan C Galofré,Amaia Rodríguez,Javier Salvador,Camilo Silva

doi:10.3390/jcm8060878

Abstract

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor (TGF)-β superfamily which declines with age and has been proposed as an anti-aging factor with regenerative effects in skeletal muscle in mice. However, recent data in humans and mice are conflicting, casting doubts about its true functional actions. The aim of the present study was to analyze the potential involvement of GFD11 in energy homeostasis in particular in relation with thyroid hormones. Serum concentrations of GDF11 were measured by enzyme-linked immunosorbent assay (ELISA) in 287 subjects. A highly significant positive correlation was found between GDF11 and thyroid-stimulating hormone (TSH) concentrations (r = 0.40, p < 0.001). Neither resting energy expenditure (REE) nor REE per unit of fat-free mass (REE/FFM) were significantly correlated (p > 0.05 for both) with GDF11 levels. In a multiple linear regression analysis, the model that best predicted logGDF11 included logTSH, leptin, body mass index (BMI), age, and C-reactive protein (logCRP). This model explained 37% of the total variability of logGDF11 concentrations (p < 0.001), with only logTSH being a significant predictor of logGDF11. After segregating subjects by TSH levels, those within the low TSH group exhibited significantly decreased (p < 0.05) GDF11 concentrations as compared to the normal TSH group or the high TSH group. A significant correlation of GDF11 levels with logCRP (r = 0.19, p = 0.025) was found. GDF11 levels were not related to the presence of hypertension or cardiopathy. In conclusion, our results show that circulating concentrations of GDF11 are closely associated with TSH concentrations and reduced in subjects with low TSH levels. However, GDF11 is not related to the regulation of energy expenditure. Our data also suggest that GDF11 may be involved in the regulation of inflammation, without relation to cardiac function. Further research is needed to elucidate the role of GDF11 in metabolism and its potential involvement in thyroid pathophysiology.

Highlights

Thyroid hormones are involved in the regulation of basal metabolic rate and are active players in many physiological processes, such as growth, development, as well as energy expenditure [1]
In the present study we observed a lack of correlation between the circulating concentrations of Growth differentiation factor 11 (GDF11) and resting energy expenditure (REE), which suggest that GDF11 is not involved in energy homeostasis
In agreement with this finding, we have previously observed that there are no differences in serum GDF11 concentrations in obese subjects as compared to lean ones [13], GDF11 levels are correlated with body mass index (BMI) and waist circumference

Summary

Introduction

Thyroid hormones are involved in the regulation of basal metabolic rate and are active players in many physiological processes, such as growth, development, as well as energy expenditure [1]. It has been shown that basal metabolism is very sensitive to thyroid hormones, with the dysregulation of the thyroid axis leading to marked alterations in energy balance [1,2]. Thyroid hormone signaling takes place peripherally, mostly in the liver, white and brown adipose tissues, and centrally, in the hypothalamus [1,2]. Thyroid hormones directly stimulate energy expenditure changing the functionality and increasing the expression of genes involved in thermogenesis, such as uncoupling protein 1, in peripheral tissues such as skeletal muscle and brown adipose tissue (BAT), and through central actions [3]

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