Abstract

Aim: Magnetic resonance imaging (MRI) is increasingly being used to evaluate brown adipose tissue (BAT) function. Reports on the extent and direction of cold-induced changes in MRI fat fraction and estimated BAT volume vary between studies. Here, we aimed to explore the effect of different fat fraction threshold ranges on outcomes measured by MRI. Moreover, we aimed to investigate the effect of cold exposure on estimated BAT mass and energy content.Methods: The effects of cold exposure at different fat fraction thresholding levels were analyzed in the supraclavicular adipose depot of nine adult males. MRI data were reconstructed, co-registered and analyzed in two ways. First, we analyzed cold-induced changes in fat fraction, T2* relaxation time, volume, mass, and energy of the entire supraclavicular adipose depot at different fat fraction threshold levels. As a control, we assessed fat fraction differences of deltoid subcutaneous adipose tissue (SAT). Second, a local analysis was performed to study changes in fat fraction and T2* on a voxel-level. Thermoneutral and post-cooling data were compared using paired-sample t-tests (p < 0.05).Results: Global analysis unveiled that the largest cold-induced change in fat fraction occurred within a thermoneutral fat fraction range of 30–100% (−3.5 ± 1.9%), without changing the estimated BAT volume. However, the largest cold-induced changes in estimated BAT volume were observed when applying a thermoneutral fat fraction range of 70–100% (−3.8 ± 2.6%). No changes were observed for the deltoid SAT fat fractions. Tissue energy content was reduced from 126 ± 33 to 121 ± 30 kcal, when using a 30–100% fat fraction range, and also depended on different fat fraction thresholds. Voxel-wise analysis showed that while cold exposure changed the fat fraction across nearly all thermoneutral fat fractions, decreases were most pronounced at high thermoneutral fat fractions.Conclusion: Cold-induced changes in fat fraction occurred over the entire range of thermoneutral fat fractions, and were especially found in lipid-rich regions of the supraclavicular adipose depot. Due to the variability in response between lipid-rich and lipid-poor regions, care should be taken when applying fat fraction thresholds for MRI BAT analysis.

Highlights

  • The main function of brown adipose tissue (BAT) is to convert chemical energy stored within lipids into thermal energy

  • When binned into 10% fat fraction (FF) intervals, this resulted in significant increases in estimated BAT volume above a FF of 30%, while the estimated BAT volume was significantly decreased above a FF of 80% (Figure 2B)

  • With increasing lower FF threshold values, Estimated BAT volume (VolBAT) decreased upon cold exposure

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Summary

Introduction

The main function of brown adipose tissue (BAT) is to convert chemical energy stored within lipids into thermal energy (heat). Upon adrenergic stimulation by sympathetic nerves, intracellular lipolysis takes place within brown adipocytes [2], and the resulting free fatty acids bind to uncoupling protein 1 (UCP1), which, in turn, functions as a molecular gate that dissipates the generated mitochondrial proton gradient as heat. Visualization of BAT by magnetic resonance imaging (MRI) was first reported almost three decades ago [5], and soon the technique was shown to accurately reflect the tissue structure [6] as well as histological changes due to temperature acclimatization [7]. In the intrascapular BAT of rodents kept on regular chow and at room temperature (circa 21◦C), MRI estimations of FF vary between 20 and 50%, depending on the depth of the tissue [12]. There is a remarkable lack of distinguishable borders for e.g., the supraclavicular depot, which makes it difficult for a consensus to be reached on the optimal FF thresholds that should be Abbreviations: BAT, Brown adipose tissue; FF, Fat fraction; FFGlob, Supraclavicular adipose tissue fat fraction estimated by global analysis; FFLoc, Fat fraction on a voxel-level; FFSAT, Fat fraction of the subcutaneous adipose tissue depot; MRI, Magnetic resonance imaging; ROIs, Regions of interest; T2∗, Mono-exponential effective transverse relaxation time; T2∗Glob, Mono-exponential effective transverse relaxation time estimated by global analysis; T2∗Loc, Monoexponential effective transverse relaxation time estimated on a voxel-level; VolBAT, Estimated BAT volume; WAT, White adipose tissue; SAT, Subcutaneous adipose tissue

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