Rationale and Objectives
The objective of this study was to assess the relationship of brown adipose tissue (BAT) activity with different fat compartments of the body, body mass index (BMI), outdoor temperature, thyroid-stimulating hormone (TSH) levels, blood glucose, age, and sex in a large patient population using F-18-fluordesoxyglucose positron emission tomography-computer tomography (FDG-PET/CT) scans obtained under thermoneutral conditions.
Materials and Methods
FDG-PET/CT scans of 4852 patients were retrospectively analyzed for BAT activity. The volumes of the different fat compartments visceral adipose tissue (VAT), subcutaneous adipose tissue (SCAT), and liver fat, were assessed by computed tomography. Age, sex, TSH levels, blood glucose levels, BMI, primary disease, and the outdoor temperature were determined. Multiple linear regression analyses were performed to identify independent relationships between the parameters.
Results
The VAT, SCAT, and liver fat content were lower in BAT-positive patients than in BAT-negative patients (each P < 0.0001). BAT-positive patients had a lower BMI ( P < 0.0001) and were more often female ( P < 0.0001), younger ( P < 0.0001), and had higher TSH levels ( P = 0.0002), whereas the outdoor temperature and the blood glucose level were not different compared to BAT-negative patients. Age, sex, VAT, and SCAT were independent factors related to BAT.
Conclusions
Age, sex, and VAT are the most important determinants of BAT activity under thermoneutral conditions. VAT reflects the association between BAT activity and body fat mass more clearly than BMI. The strength of the association between VAT and BAT decreases during aging in men, but increases in women. This may indicate a different importance of BAT activity for obesity in men and in women.
Introduction
Brown adipose tissue (BAT) is exclusively found in mammals and generates heat to protect animals from hypothermia . For a long time, it was thought that BAT is present in humans only in newborns, until it was found to be present also in about 5%–10% of adults under thermoneutral conditions . BAT activity is increased upon cold activation . However, whereas cold-activated BAT was found in approximately 50% of younger subjects, it was merely found in 10% of older people .
BAT has the function of nonshivering thermogenesis. Being activated by the sympathetic nervous system, BAT has a high glucose and fatty acid consumption . This increase in BAT-associated expenditure is thought to have positive effects on body fat mass . In agreement with this notion, BAT mass and activity are negatively associated with the body mass index (BMI), the total fat mass, and the mass of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SCAT) . In particular, the body fat compartment VAT is related to obesity-related disorders . In addition, increased BAT mass and activity are thought to be associated with improved glucose and lipid metabolism . Consequently, activation of BAT is accompanied by increased insulin sensitivity and diminished glucose levels, although this association is not confirmed consistently in published data . Interestingly, although cold exposure can strongly induce BAT activity and cold-induced thermogenesis in young adults, the effects on body fat mass are small . Furthermore, it is not realistic that cold exposure will become a widely applied tool to treat obesity and its metabolic consequences in the clinical setting. This raises the question as to what extent BAT mass and activity associate with different body compartments, liver fat (LF) content, and glucose levels under thermoneutral conditions. As further regulators, thyroid hormones have been shown to induce BAT activity in mice and in men .
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Materials and Methods
Patients
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FDG-PET/CT Examination
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Image Analysis and Data Collection
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Statistical Analysis
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Results
Whole Patient Group
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TABLE 1
Relationship of Patient Characteristics and Temperature with BAT Activity
Characteristics Spearman Correlation r Spearman Correlation P Value Multiple Linear Regression P Value Sex <0.0001 Age −0.3851 <0.0001 \* <0.0001 BMI −0.3336 <0.0001 \* n.s. TSH 0.1326 0.0035 \* n.s. Blood glucose −0.0976 0.0168 n.s. Temperature −0.0473 0.2464 n.s. VAT −0.5060 <0.0001 \* 0.0344 LF −0.2902 <0.0001 \* n.s. SCAT −0.2344 <0.0001 \* 0.0314
BMI, body mass index; LF, liver fat; n.s., not significant; SCAT, subcutaneous adipose tissue; TSH, thyroid-stimulating hormone; VAT, visceral adipose tissue.
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Subgroups Divided by Age
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TABLE 2
Association Between Patient Characteristics and BAT Activity in Subgroups by Age
Age Group Characteristics Spearman Correlation r Spearman Correlation P Value Multiple Linear Regression P Value Tertile 1 ( n = 201) BMI −0.2960 <0.0001 \* n.s. TSH 0.2142 0.0089 n.s. Blood glucose −0.0337 0.6364 n.s. VAT −0.3466 <0.0001 \* <0.0001 LF −0.1679 0.0543 n.s. SCAT −0.2085 0.0031 \* n.s. Tertile 2 ( n = 200) BMI −0.2967 <0.0001 \* n.s. TSH 0.0093 0.9043 n.s. Blood glucose −0.0085 0.9045 n.s. VAT −0.4423 <0.0001 \* <0.0001 LF −0.3458 <0.0001 \* n.s. SCAT −0.1630 0.0211 n.s. Tertile 3 ( n = 201) BMI −0.2107 0.0027 \* n.s. TSH −0.0414 0.8376 n.s. Blood glucose −0.0251 0.7239 n.s. VAT −0.4283 <0.0001 \* <0.0001 LF −0.2112 0.0079 \* n.s. SCAT −0.1354 0.0553 n.s.
BMI, body mass index; LF, liver fat; n.s., not significant; SCAT, subcutaneous adipose tissue; TSH, thyroid-stimulating hormone; VAT, visceral adipose tissue.
Tertile 1: age 5–44 years; tertile 2: age 44–57 years; tertile 3, 57–82 years.
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Subgroups Divided by Sex
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TABLE 3
Association Between Patient Characteristics and BAT Activity in Subgroups by Sex
Sex Characteristics Spearman Correlation r Spearman Correlation P Value Multiple Linear Regression P Value Male ( n = 304) BMI −0.3340 <0.0001 \* n.s. TSH 0.0998 0.1778 n.s. Blood glucose −0.0730 n.s. n.s. VAT −0.4945 <0.0001 \* <0.0001 LF −0.2750 <0.0001 \* 0.0386 SCAT −0.3902 <0.0001 \* n.s. Female ( n = 298) BMI −0.2402 <0.0001 \* n.s. TSH 0.1731 0.0076 \* n.s. Blood glucose −0.0990 n.s. n.s. VAT −0.3433 <0.0001 \* <0.0001 LF −0.2765 <0.0001 \* n.s. SCAT −0.2131 0.0012 \* n.s.
BMI, body mass index; LF, liver fat; n.s., not significant; SCAT, subcutaneous adipose tissue; TSH, thyroid-stimulating hormone; VAT, visceral adipose tissue.
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Subgroups Divided by Age and Sex
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TABLE 4
Association Between Patient Characteristics and BAT Activity in Subgroups by Age and Sex
Subgroup Characteristics Spearman Correlation r Spearman Correlation P Value Multiple Linear Regression P Value Male tertile 1 ( n = 108) BMI −0.3404 0.0003 \* n.s. TSH 0.3699 0.0007 \* n.s. Blood glucose 0.0789 0.4189 n.s. VAT −0.4319 <0.0001 \* <0.0001 LF −0.2322 0.0549 n.s. SCAT −0.3692 <0.0001 \* n.s. Male tertile 2 ( n = 93) BMI −0.2447 0.0181 n.s. TSH −0.2186 0.0514 n.s. Blood glucose 0.0259 0.8056 n.s. VAT −0.3560 0.0005 \* 0.0004 LF −0.1936 0.1418 n.s. SCAT −0.3295 0.0013 \* n.s. Male tertile 3 ( n = 103) BMI −0.1001 0.3142 n.s. TSH −0.1698 0.1159 n.s. Blood glucose −0.0213 0.8311 n.s. VAT −0.2934 0.0026 \* n.s. LF −0.0948 0.4091 n.s. SCAT −0.1693 0.0874 0.0385 Female tertile 1 ( n = 93) BMI −0.2032 0.0507 n.s. TSH 0.0920 0.4556 n.s. Blood glucose −0.1679 0.1097 n.s. VAT −0.1329 0.2067 n.s. LF −0.1679 0.1885 n.s. Female tertile 2 ( n = 107) BMI −0.1892 0.0510 n.s. TSH 0.1815 0.0852 n.s. Blood glucose 0.0077 0.9373 n.s. VAT −0.2558 0.0078 \* 0.0443 LF −0.3957 0.0002 \* 0.0149 SCAT −0.1668 0.0860 n.s. Female tertile 3 ( n = 98) BMI −0.1764 0.0839 n.s. TSH 0.0804 0.4842 n.s. Blood glucose 0.0518 0.6123 n.s. VAT −0.3614 0.0003 \* 0.0369 LF −0.2614 0.0200 n.s. SCAT −0.2283 0.0237 n.s.
BMI, body mass index; LF, liver fat; n.s., not significant; SCAT, subcutaneous adipose tissue; TSH, thyroid-stimulating hormone; VAT, visceral adipose tissue.
Tertile 1: age 5–44 years; tertile 2: age 44–57 years; tertile 3, 57–82 years.
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Discussion
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Acknowledgment
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