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Clinical Trial
, 114 (32), 8649-8654

Mapping of Human Brown Adipose Tissue in Lean and Obese Young Men

Affiliations
Clinical Trial

Mapping of Human Brown Adipose Tissue in Lean and Obese Young Men

Brooks P Leitner et al. Proc Natl Acad Sci U S A.

Abstract

Human brown adipose tissue (BAT) can be activated to increase glucose uptake and energy expenditure, making it a potential target for treating obesity and metabolic disease. Data on the functional and anatomic characteristics of BAT are limited, however. In 20 healthy young men [12 lean, mean body mass index (BMI) 23.2 ± 1.9 kg/m2; 8 obese, BMI 34.8 ± 3.3 kg/m2] after 5 h of tolerable cold exposure, we measured BAT volume and activity by 18F-labeled fluorodeoxyglucose positron emission tomography/computerized tomography (PET/CT). Obese men had less activated BAT than lean men (mean, 130 vs. 334 mL) but more fat in BAT-containing depots (mean, 1,646 vs. 855 mL) with a wide range (0.1-71%) in the ratio of activated BAT to inactive fat between individuals. Six anatomic regions had activated BAT-cervical, supraclavicular, axillary, mediastinal, paraspinal, and abdominal-with 67 ± 20% of all activated BAT concentrated in a continuous fascial layer comprising the first three depots in the upper torso. These nonsubcutaneous fat depots amounted to 1.5% of total body mass (4.3% of total fat mass), and up to 90% of each depot could be activated BAT. The amount and activity of BAT was significantly influenced by region of interest selection methods, PET threshold criteria, and PET resolutions. The present study suggests that active BAT can be found in specific adipose depots in adult humans, but less than one-half of the fat in these depots is stimulated by acute cold exposure, demonstrating a previously underappreciated thermogenic potential.

Keywords: PET/CT; brown fat; metabolism; obesity.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
(A and B) Comparison of SUV values of metabolically active tissues normalized to TBM (A) vs. LBM (B) as measured by DXA. ROIs were drawn on the right pectoralis major, segment VII of the right lobe of the liver, and the right cerebellum (tissue ROI locations in Fig. S3). (C) BAT volumes using SUV normalized to TBM vs. to LBM. SUVTBM lower threshold, ≥1.5 g/mL for all subjects; SUVLBM lower threshold, ≥1.2/ LBM% g/mL. #P values calculated by the Mann–Whitney U test. *P values calculated using the paired t test.
Fig. S1.
Fig. S1.
Changes in detected BAT activity after correction to LBM. SUVTBM was calculated with an SUV lower threshold ≥1.5 g/mL. SUVLBM was calculated using the following equation: SUVLBM = 1.2/LBM%. *By the paired t test. #By the Mann–Whitney U test.
Fig. S2.
Fig. S2.
Interobserver reproducibility of coronal and axial ROI selection methods. Shown are correlation for coronal method-quantified BAT volume (A) and activity (C), and correlation for axial method- quantified BAT volume (B) and activity (D).
Fig. 2.
Fig. 2.
Detected BAT volume quantified by axial and coronal ROI methods. (A) ROI selections for coronal and axial views (red lines). (B) Detected BAT shown in blue pixels. (C) Detected BAT volume for all subjects comparing coronal vs. axial methods. P value calculated by the Mann–Whitney U test. (D) Correlation between axial and coronal BAT volume quantifications.
Fig. 3.
Fig. 3.
Observed tissue SUVmax values of varying metabolic activity with PET resolutions of 7.0 and 3.5 mm (n = 8). Tissue ROI locations in Fig. S3. (A) Mean values with SD. *P < 0.05, two-way ANOVA. (B) Ratio of SUVmax obtained from 3.5 to 7.0 mm.
Fig. S3.
Fig. S3.
Regional locations for BAT and non-BAT tissues for Figs. 1 and 4. 1, scWAT; 2, skeletal muscle (deltoid); 3, liver (right lobe); 4, heart (left ventricle); 5, cerebellum (right side); 6, supraclavicular BAT; 7, axillary BAT.
Fig. 4.
Fig. 4.
Distribution and capacity of human BAT. (A) Regional distribution of BAT in six anatomic depots. (B) Average (SD) amount of activated and brownable inactive fat in the defined depots. (C) Summed active and brownable tissue in 12 lean subjects and 8 obese subjects. Empty and dotted bars in B and C represent volumes of the entire adipose tissue depots in which active BAT was found. The solid colored bars in B represent the volume of activated BAT within each adipose tissue depot, and the solid black bars in C represent the total activated BAT found in the body.
Fig. S4.
Fig. S4.
BAT distribution across all 20 subjects. (A) BAT distribution was measured in 300 bins averaged to correct for differences in height. Volume is displayed along the body, with each of all 20 subjects identified with a different line and arranged from lowest to highest total body BAT volume. Regions are specified along the vertebrae on the x-axis. (B) Proportion of adipose tissue in each depot as activated BAT in lean men (n = 12) and obese men (n = 8).
Fig. S5.
Fig. S5.
Activated BAT in adipose depot. Red regions indicate active BAT; blue regions indicate remaining adipose tissue within defined BAT depots. Quantification values are shown in Fig. 4.
Fig. 5.
Fig. 5.
scWAT and BAT in a patient with confirmed paraganglioma. (A) Frontal and (B) sagittal views of PET maximum intensity projection, with red lines indicating the axial slices shown in C and D. (C) Fused PET/CT image and (D) CT image alone showing 1, active BAT; 2, subcutaneous WAT; 3, inactive omental fat.

Comment in

  • Obesity: New insights into BAT activity.
    Morris A. Morris A. Nat Rev Endocrinol. 2017 Oct;13(10):563. doi: 10.1038/nrendo.2017.107. Epub 2017 Aug 11. Nat Rev Endocrinol. 2017. PMID: 28799553 No abstract available.

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