Effects of intravenous thyrotropin-releasing hormone on 18F-fluorodeoxyglucose uptake in human brown adipose tissue: a randomized controlled trial

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Abstract
Objective: Brown adipose tissue (BAT) activity in humans is stimulated by cold and by a limited number of pharmacological agents, including β3-adrenergic agonists and bile acids. Although thyrotropin-releasing hormone (TRH) is known to activate BAT in several mammals, this has not been reported in humans. Design: A randomized, placebo-controlled, double blind, cross-over trial. Methods: We investigated the effects of intravenous bolus administration of 400 µg TRH or 2 mL saline on BAT activity in healthy, lean men. BAT activity was measured as standardized 18F-fluorodeoxyglucose (18F-FDG) uptake and glucose metabolic rate (MRglu) using dynamic positron emission tomography (PET)/computed tomography (CT) imaging. The first six individuals were studied at room temperature, while subsequently nine were exposed to mild cold (17°C ±1°C) for 60 minutes before imaging. During the dynamic scan, blood was withdrawn for measurement of thyroid hormone and catecholamine concentrations. This trial is registered with The Netherlands National Trial Register (number NTR5512). Results: Sixteen participants were recruited. Six men studied at room temperature showed no visible BAT activity during either session. After exposure to mild cold, four of nine men (44.4%) showed clear increase of 18F-FDG uptake after TRH administration compared to placebo. Maximal standardized 18F-FDG uptake showed a trend towards increase after TRH compared to placebo (p= 0.066). MRglu showed a significant increase after TRH administration (p= 0.014). The increase in 18F-FDG uptake was not paralleled by changes in plasma thyroid hormone or catecholamine concentrations. Conclusion: Systemic TRH administration can increase the activity of cold-stimulated BAT in adult men. These findings may assist developing pharmacological strategies for modulating BAT activity in the management of obesity.

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