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

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.

Sympathetic Innervation of Cold-Activated Brown and White Fat in Lean Young Adults

“…These values are consistent with recent tracer experiments showing that the energy content of glucose (27) or nonesterified fatty acids (32) taken up by active BAT is trivial when compared with cold-induced energy expenditure (33). Finally, the energy content of cold-induced glucose uptake in human BAT was reported by various investigators (6,27,34) to amount to less than 10 kcal/d if fully oxidized, in agreement with our findings.…”

“…Furthermore, activation of human BAT depots appears to be selectively induced by cold stress, but not by nonselective sympathomimetic activation (4). Nonetheless, these PET-defined BAT depots account for less than 5% of the total cold-induced increase in metabolism, an observation supported by other recent reports (34,35). Moreover, these investigators have also presented data that suggest that deep, centrally located muscles of the neck, back, and inner thigh are the greatest contributors to cold-induced thermogenesis via activation of muscle shivering on a microscale level, with BAT possibly assuming a more endocrine role.…”

Regulation of human brown adipose tissue by adenosine and A2A receptors – studies with [15O]H2O and [11C]TMSX PET/CT

“…Electrocardiography was monitored during the cooling protocol and blood samples were acquired before and after cooling. Indirect calorimetry was performed using a Deltatrac II Datex-Ohmeda monitor at baseline and during cold conditions to measure whole-body EE according to the Weir equation [22] as previously described [10]. …”

“…The objectives of this study were, firstly, to investigate the effects of adenosine on human BAT perfusion and, secondly, to quantify the density of A2AR in BAT in different physiological states. Radiowater, [ 15 O]H 2 O, is commonly used to investigate tissue perfusion, and BAT perfusion is directly associated with oxygen consumption and EE [10–12]. [ 15 O]H 2 O-PET imaging during adenosine administration has previously been used to study human skeletal muscle, cardiovascular function and WAT [13–15], but not BAT.…”

The role of BAT in cardiometabolic disorders and aging

“…Obviously, the shivering response participates to the cold-induced thermogenic response and confounds the interpretation of the role of BAT in this process, especially given the large bulk of skeletal muscles compared to the small volume of BAT. Data from a recent study using [ 15 O]O 2 PET imaging [45] suggests that, assuming a mean tissue-specific oxygen consumption of skeletal muscle during a mild cold exposure (1.2 Â resting metabolic rate) of 0.34 mL/100 g/min, a 72 kg man with a muscle mass estimated as 42% of body mass (30 kg, see [121]), shivering thermogenesis would represent~40% of whole-body energy expenditure (or 821 kcal/day), a doubling of the resting muscle contribution seen at room temperature. Interestingly, although cold acclimation results in a near abolishment of shivering thermogenesis in favour of BAT thermogenesis in rodents, such a phenomenon has not been shown in humans using EMG [44].…”