Human brown adipose tissue [(15)O]O2 PET imaging in the presence and absence of cold stimulus.

Mueez U Din,Hannu T Sipilä,Tuula Tolvanen,Nina Savisto,Kirsi A Virtanen,Pirjo Nuutila,Teemu Saari,Riitta Parkkola,Jarmo Teuho,Vesa Oikonen,Nobu Kudomi,Juho Raiko

doi:10.1007/s00259-016-3364-y

Abstract

PurposeBrown adipose tissue (BAT) is considered a potential target for combatting obesity, as it produces heat instead of ATP in cellular respiration due to uncoupling protein-1 (UCP-1) in mitochondria. However, BAT-specific thermogenic capacity, in comparison to whole-body thermogenesis during cold stimulus, is still controversial. In our present study, we aimed to determine human BAT oxygen consumption with [15O]O2 positron emission tomography (PET) imaging. Further, we explored whether BAT-specific energy expenditure (EE) is associated with BAT blood flow, non-esterified fatty acid (NEFA) uptake, and whole-body EE.MethodsSeven healthy study subjects were studied at two different scanning sessions, 1) at room temperature (RT) and 2) with acute cold exposure. Radiotracers [15O]O2, [15O]H2O, and [18F]FTHA were given for the measurements of BAT oxygen consumption, blood flow, and NEFA uptake, respectively, with PET-CT. Indirect calorimetry was performed to assess differences in whole-body EE between RT and cold.ResultsBAT-specific EE and oxygen consumption was higher during cold stimulus (approx. 50 %); similarly, whole-body EE was higher during cold stimulus (range 2–47 %). However, there was no association in BAT-specific EE and whole-body EE. BAT-specific EE was found to be a minor contributor in cold induced whole-body thermogenesis (almost 1 % of total whole-body elevation in EE). Certain deep muscles in the cervico-thoracic region made a major contribution to this cold-induced thermogenesis (CIT) without any visual signs or individual perception of shivering. Moreover, BAT-specific EE associated with BAT blood flow and NEFA uptake both at RT and during cold stimulus.ConclusionOur study suggests that BAT is a minor and deep muscles are a major contributor to CIT. In BAT, both in RT and during cold, cellular respiration is linked with circulatory NEFA uptake.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-016-3364-y) contains supplementary material, which is available to authorized users.

Highlights

Brown adipose tissue (BAT) provides non-shivering thermogenesis (NST) because of the presence of the mitochondrial uncoupling protein-1(UCP-1) [1] and BAT activity remains present in humans in adulthood [2,3,4]
BAT-specific EE and oxygen consumption was higher during cold stimulus; whole-body EE was higher during cold stimulus
BAT-specific EE associated with BAT blood flow and NEFA uptake both at room temperature (RT) and during cold stimulus

Summary

Introduction

Brown adipose tissue (BAT) provides non-shivering thermogenesis (NST) because of the presence of the mitochondrial uncoupling protein-1(UCP-1) [1] and BAT activity remains present in humans in adulthood [2,3,4]. Previous studies showing metabolically active BAT under cold stress are based on high symmetrical bilateral [18F]FDG uptake in supraclavicular adipose tissue regions [6,7,8,9], while active BAT is considered to rely primarily on fatty acids as the major fuel for thermogenesis [10]. The study by Muzik et al [11] has shown that during cold stress higher [18F]FDG. It was critical to confirm BAT-specific EE using direct oxygen consumption measurements by using [15O]O2 positron-emission tomography (PET) imaging. It has not yet been established how much of the BAT circulatory NEFA uptake is associated with BAT-specific thermogenesis

Objectives

Methods

Results

Conclusion