Correlation of Brown Adipose Tissue with Other Body Fat Compartments and Patient Characteristics: A Retrospective Analysis in a Large Patient Cohort Using PET/CT

doi:10.1016/j.acra.2017.09.007

Academic Radiology

Volume 25, Issue 1, January 2018, Pages 102-110

https://doi.org/10.1016/j.acra.2017.09.007 Get rights and content

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 (1). 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 2, 3, 4, 5. BAT activity is increased upon cold activation 6, 7, 8. However, whereas cold-activated BAT was found in approximately 50% of younger subjects, it was merely found in 10% of older people (9).

BAT has the function of nonshivering thermogenesis. Being activated by the sympathetic nervous system, BAT has a high glucose and fatty acid consumption 10, 11. This increase in BAT-associated expenditure is thought to have positive effects on body fat mass (12). 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) 6, 8, 9, 13. In particular, the body fat compartment VAT is related to obesity-related disorders (14). In addition, increased BAT mass and activity are thought to be associated with improved glucose and lipid metabolism 15, 16, 17. Consequently, activation of BAT is accompanied by increased insulin sensitivity and diminished glucose levels, although this association is not confirmed consistently in published data 2, 13, 15, 18. Interestingly, although cold exposure can strongly induce BAT activity and cold-induced thermogenesis in young adults, the effects on body fat mass are small (19). 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 20, 21.

Therefore, the aim of our study was to analyze the relationship between BAT and body fat distribution measured by VAT, SCAT mass, and LF content in a large population of nononcological and oncological patients in a clinical routine setup using F-18-fluordesoxyglucose positron emission tomography-computer tomography (FDG-PET/CT). Furthermore, the association of BAT with the outdoor temperature, thyroid-stimulating hormone (TSH), blood glucose, BMI, age, and sex was assessed. Additionally, the patients were divided into subgroups regarding age and sex, and the strengths of these relationships in the subgroups were compared in detail.

Section snippets

Patients

Data of a total of 4852 patients who underwent clinically indicated FDG-PET/CT scans between August 2004 and July 2009 at our institution, located in Germany, in the temperate climate zone, were evaluated concerning the presence of active BAT. The patient collective included pediatric patients in a small percentage. Definition criteria for the presence of active BAT were areas in PET scans with symmetric paravertebral, nuchal, supra- or infraclavicular FDG uptake, a maximum standardized uptake

Whole Patient Group

A total of 263 of 4852 FDG-PET/CT scans (5.4%) were BAT positive. Data from 227 BAT-positive and 375 BAT-negative patients were included in the final evaluation (mean age 49 ± 16 years, 304 male, 298 female; see patients' flowchart in Fig 1). Within the included patients were 31 pediatric patients below the age of 18 (mean 14 ± 3 years, range 5–17 years, 12 female, 19 male). A total of 430 nonenhanced CT datasets were available for the assessment of LF (mean age 50 ± 16 years, 206 male, 224

Discussion

BAT has been proposed to be a potential target for the treatment of obesity by increasing the energy expenditure under activation, although its definite role in the complex pathophysiology of obesity is not yet clear 9, 17, 23, 24. In this context, it is important to know which factors are associated with active BAT and possibly influence BAT activation.

The negative associations of BAT activity with age and a high BMI as well as the higher amount of BAT activation in females are well known and

Acknowledgment

The authors thank Juergen Machann for providing a software script for the segmentation of different fat compartments in imaging datasets.

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Original InvestigationCorrelation of Brown Adipose Tissue with Other Body Fat Compartments and Patient Characteristics: A Retrospective Analysis in a Large Patient Cohort Using PET/CT

Rationale and Objectives

Materials and Methods

Results

Conclusions

Introduction

Section snippets

Patients

Whole Patient Group

Discussion

Acknowledgment

Mol Cell Endocrinol

Cell Metab

Pharmacol Ther

Cell Metab

Cell

J Pediatr

J Pediatr

Cell Metab

Brown adipose tissue: function and physiological significance

Physiol Rev

Identification and importance of brown adipose tissue in adult humans

N Engl J Med

A new era in brown adipose tissue biology: molecular control of brown fat development and energy homeostasis

Annu Rev Physiol

Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans

J Clin Endocrinol Metab

Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans

Diabetes

Cold-activated brown adipose tissue in healthy men

N Engl J Med

Functional brown adipose tissue in healthy adults

N Engl J Med

High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity

Diabetes

Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans

Obesity (Silver Spring)

Ephedrine activates brown adipose tissue in lean but not obese humans

Diabetologia

Brown adipose tissue: what have we learned since its recent identification in human adults

Arq Bras Endocrinol Metabol

Impact of brown adipose tissue on body fatness and glucose metabolism in healthy humans

Int J Obes

Pathophysiology of human visceral obesity: an update

Physiol Rev

Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus

Nat Med

Original Investigation
Correlation of Brown Adipose Tissue with Other Body Fat Compartments and Patient Characteristics: A Retrospective Analysis in a Large Patient Cohort Using PET/CT