Effects of intravenous thyrotropin-releasing hormone on18F-fluorodeoxyglucose uptake in human brown adipose tissue: a randomized controlled trial

Charlotte A. Heinen, Zhi Zhang, Lars P. Klieverik, Tim C. de Wit, Edwin Poel, Maqsood Yaqub, Anita Boelen, Andries Kalsbeek, Peter H. Bisschop, A. S. Paul van Trotsenburg, Hein J. Verberne, Jan Booij, Eric Fliers

Research output: Contribution to journalArticleAcademicpeer-review

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 400µg TRH or 2mL saline on BAT activity in healthy, lean men. BAT activity was measured as standardized18F-fluorodeoxyglucose (18F-FDG) uptake and glucose metabolic rate (MRglu) using dynamic PET/CT imaging. The first six individuals were studied at room temperature, while subsequently nine were exposed to mild cold (17°C±1°C) for 60min 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 During the dynamic scan, blood was withdrawn for measurement of thyroid hormone and catecholamine concentrations.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 of18F-FDG uptake after TRH administration compared to placebo. Maximal standardized18F-FDG uptake showed a trend toward increase after TRH compared to placebo (P=0.066). MRglu showed a significant increase after TRH administration (P=0.014). The increase in18F-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.
Original languageEnglish
Pages (from-to)31-38
JournalEuropean Journal of Endocrinology
Volume179
Issue number1
DOIs
Publication statusPublished - 2018

Cite this

Heinen, Charlotte A. ; Zhang, Zhi ; Klieverik, Lars P. ; de Wit, Tim C. ; Poel, Edwin ; Yaqub, Maqsood ; Boelen, Anita ; Kalsbeek, Andries ; Bisschop, Peter H. ; van Trotsenburg, A. S. Paul ; Verberne, Hein J. ; Booij, Jan ; Fliers, Eric. / Effects of intravenous thyrotropin-releasing hormone on18F-fluorodeoxyglucose uptake in human brown adipose tissue: a randomized controlled trial. In: European Journal of Endocrinology. 2018 ; Vol. 179, No. 1. pp. 31-38.
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title = "Effects of intravenous thyrotropin-releasing hormone on18F-fluorodeoxyglucose uptake in human brown adipose tissue: a randomized controlled trial",
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 400µg TRH or 2mL saline on BAT activity in healthy, lean men. BAT activity was measured as standardized18F-fluorodeoxyglucose (18F-FDG) uptake and glucose metabolic rate (MRglu) using dynamic PET/CT imaging. The first six individuals were studied at room temperature, while subsequently nine were exposed to mild cold (17°C±1°C) for 60min 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 of18F-FDG uptake after TRH administration compared to placebo. Maximal standardized18F-FDG uptake showed a trend toward increase after TRH compared to placebo (P=0.066). MRglu showed a significant increase after TRH administration (P=0.014). The increase in18F-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.",
author = "Heinen, {Charlotte A.} and Zhi Zhang and Klieverik, {Lars P.} and {de Wit}, {Tim C.} and Edwin Poel and Maqsood Yaqub and Anita Boelen and Andries Kalsbeek and Bisschop, {Peter H.} and {van Trotsenburg}, {A. S. Paul} and Verberne, {Hein J.} and Jan Booij and Eric Fliers",
year = "2018",
doi = "10.1530/EJE-17-0966",
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pages = "31--38",
journal = "European Journal of Endocrinology",
issn = "0804-4643",
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Effects of intravenous thyrotropin-releasing hormone on18F-fluorodeoxyglucose uptake in human brown adipose tissue: a randomized controlled trial. / Heinen, Charlotte A.; Zhang, Zhi; Klieverik, Lars P.; de Wit, Tim C.; Poel, Edwin; Yaqub, Maqsood; Boelen, Anita; Kalsbeek, Andries; Bisschop, Peter H.; van Trotsenburg, A. S. Paul; Verberne, Hein J.; Booij, Jan; Fliers, Eric.

In: European Journal of Endocrinology, Vol. 179, No. 1, 2018, p. 31-38.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Effects of intravenous thyrotropin-releasing hormone on18F-fluorodeoxyglucose uptake in human brown adipose tissue: a randomized controlled trial

AU - Heinen, Charlotte A.

AU - Zhang, Zhi

AU - Klieverik, Lars P.

AU - de Wit, Tim C.

AU - Poel, Edwin

AU - Yaqub, Maqsood

AU - Boelen, Anita

AU - Kalsbeek, Andries

AU - Bisschop, Peter H.

AU - van Trotsenburg, A. S. Paul

AU - Verberne, Hein J.

AU - Booij, Jan

AU - Fliers, Eric

PY - 2018

Y1 - 2018

N2 - 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 400µg TRH or 2mL saline on BAT activity in healthy, lean men. BAT activity was measured as standardized18F-fluorodeoxyglucose (18F-FDG) uptake and glucose metabolic rate (MRglu) using dynamic PET/CT imaging. The first six individuals were studied at room temperature, while subsequently nine were exposed to mild cold (17°C±1°C) for 60min 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 of18F-FDG uptake after TRH administration compared to placebo. Maximal standardized18F-FDG uptake showed a trend toward increase after TRH compared to placebo (P=0.066). MRglu showed a significant increase after TRH administration (P=0.014). The increase in18F-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.

AB - 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 400µg TRH or 2mL saline on BAT activity in healthy, lean men. BAT activity was measured as standardized18F-fluorodeoxyglucose (18F-FDG) uptake and glucose metabolic rate (MRglu) using dynamic PET/CT imaging. The first six individuals were studied at room temperature, while subsequently nine were exposed to mild cold (17°C±1°C) for 60min 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 of18F-FDG uptake after TRH administration compared to placebo. Maximal standardized18F-FDG uptake showed a trend toward increase after TRH compared to placebo (P=0.066). MRglu showed a significant increase after TRH administration (P=0.014). The increase in18F-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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UR - https://www.ncbi.nlm.nih.gov/pubmed/29724865

U2 - 10.1530/EJE-17-0966

DO - 10.1530/EJE-17-0966

M3 - Article

VL - 179

SP - 31

EP - 38

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

SN - 0804-4643

IS - 1

ER -