Cold exposure induces dynamic, heterogeneous alterations in human brown adipose tissue lipid content

Abstract

Brown adipose tissue undergoes a dynamic, heterogeneous response to cold exposure that can include the simultaneous synthesis, uptake, and oxidation of fatty acids. The purpose of this work was to quantify these changes in brown adipose tissue lipid content (fat-signal fraction (FSF)) using fat-water magnetic resonance imaging during individualized cooling to 3 °C above a participant’s shiver threshold. Eight healthy men completed familiarization, perception-based cooling, and MRI-cooling visits. FSF maps of the supraclavicular region were acquired in thermoneutrality and during cooling (59.5 ± 6.5 min). Brown adipose tissue regions of interest were defined, and voxels were grouped into FSF decades (0–10%, 10–20%…90–100%) according to their initial value. Brown adipose tissue contained a heterogeneous morphology of lipid content. Voxels with initial FSF values of 60–100% (P < 0.05) exhibited a significant decrease in FSF while a simultaneous increase in FSF occurred in voxels with initial FSF values of 0–30% (P < 0.05). These data suggest that in healthy young men, cold exposure elicits a dynamic and heterogeneous response in brown adipose tissue, with areas initially rich with lipid undergoing net lipid loss and areas of low initial lipid undergoing a net lipid accumulation.

Human Brown Adipose Tissue Estimated With Magnetic Resonance Imaging Undergoes Changes in Composition After Cold Exposure: An in vivo MRI Study in Healthy Volunteers

“…From this perspective, the range where FF is higher than 70% has previously been assumed to be above the BAT threshold (52). For this reason, we found it remarkable that, in our results, these high-lipid areas of the supraclavicular adipose depot actually showed the largest decrease in lipid and energy content after cold exposure, which is in agreement with recent findings (25). These data suggest that, in fact, one should not use 70% as an upper threshold, and voxels showing up to 100% FF should be used in the analysis [e.g., as performed in (22,53)].…”

“…Both the global and local analyses showed that changes occurred across the entire baseline FF range (30-100%), with the greatest apparent FF decrease when using a 34-100% FF range. The largest FF decrease we observed (i.e., 3.5%) is in the range of values reported in literature (19,21,23), but also much smaller (22) and larger decreases (25) have been reported. This could be due to the use of different thresholds, but also differences in the cooling protocols can play an important role (54,55).…”

“…in a recent study (25). This example goes against expectations of BAT only decreasing its lipid content, an idea so broadly accepted that the loss of lipids during cooling has been used as a condition sine qua non for the identification of BAT (23).…”

“…A recent report where the use of FF thresholds were also explored showed an opposite effect, as a larger effect on FF was shown using a 50% threshold compared to a 40% threshold. In their approach, FF thresholds were only applied to the thermoneutral ROIs (25), which could have enabled measuring larger FF differences with increasing lower thresholds because voxels in the post-cooling scans were not excluded. This indicates that care should be taken before excluding low-lipid areas from the analysis.…”

“…As a consequence, FF within human BAT has variously been described as circa 60% (16), 65% (17), 80% (18,19), and 94% (20) in elderly adults and different FF threshold levels have been used to segment BAT (19,(21)(22)(23)(24). Only one recent study explored the effect of specific FF threshold levels (0-100, 40-100, and 50-100%) on the cold-induced response in FF (25), but no analyses on other MR outcome parameters were explored. The relaxation time T2 * has also been studied as an indirect MRI measure of BAT activity (16,21,24,26,27).…”