Active Brown Adipose Tissue Is Associated With a Healthier Metabolic Phenotype in Obesity

Abstract

Obesity is associated with increasing cardiometabolic morbidity and mortality rates worldwide. Not everyone with obesity, however, develops metabolic complications. Brown adipose tissue (BAT) has been suggested to be a promoter of leanness and metabolic health. To date, little is known about the prevalence and metabolic function of BAT in people with severe obesity, a population at high cardiometabolic risk. In this cross-sectional study, we included 40 individuals with World Health Organization class II-III obesity (BMI ≥35 kg/m2). Using a 150-min personalized cooling protocol and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography, cold-activated BAT was detectable in 14 of the participants (35%). Cold-induced thermogenesis was significantly higher in participants with detectable BAT compared with those without. Notably, individuals with obesity and active BAT had 28.8% lower visceral fat mass despite slightly higher total fat mass compared with those without detectable BAT 18F-FDG uptake. The lower amount of visceral fat mass was accompanied by lower insulin resistance and systemic inflammation and improved nonalcoholic fatty liver disease parameters, all adjusted for age, sex, and percent body fat. Contrary to previous assumptions, we show here that a significant fraction of individuals with severe obesity has active BAT. We found that decreased BAT 18F-FDG uptake was not associated with adiposity per se but with higher visceral fat mass. In summary, active BAT is linked to a healthier metabolic phenotype in obesity.

Brown Adipose Tissue Prevalence Is Lower in Obesity but Its Metabolic Activity Is Intact

“…After the second indirect calorimetry volunteers received 2.5 Megabecquerel per kilogram of bodyweight of 18 F-fluorodeoxyglucose ( 18 F-FDG) intravenously followed by another 60 minutes of cold exposure during the tracer uptake. Then, a combined PET/CT acquisition was started as previously described ( 8 , 17 ). The study participants underwent a total of 180 minutes cold exposure.…”

“…The PET/CT images were analyzed as previously described ( 8 ). Briefly, the regions of interest were delineated in the axial fusion images using a semi-automated segmentation protocol in accordance with the BARCIST criteria ( 5 ).…”

“…Based on the uptake of the glucose analog 18 F-FDG in deep cervical, supraclavicular, axillary, mediastinal and paraspinal fat depots in participants undergoing standardized cooling protocols, we gathered a large body of knowledge about the prevalence, plasticity and potential metabolic benefits of human BAT during the last decade ( 6 ). The prevalence of active BAT decreases with age, the degree of adiposity as well as with impaired glucose and lipid metabolism ( 7 , 8 ). BAT activity depends on seasonal variation and it can be recruited by chronic intermittent cooling protocols with potential benefits on body fat distribution and nutrient handling ( 9 – 13 ).…”

“…Whereas single studies have reported a negative association between obesity and the frequency of active BAT, systematic data on the prevalence and metabolic activity of BAT comparing lean and obese individuals are lacking. Particularly, the previous assumption that BAT is dysfunctional in obesity has recently been challenged ( 8 , 16 ). In general, between-study comparability is poor due to different thresholding strategies and different regions of interest in addition to different cooling protocols.…”

Immune Cells in Thermogenic Adipose Depots: The Essential but Complex Relationship

“…Thus, both brown and beige fat tissues have thermogenic potential and will be referred to as thermogenic adipose tissues (TAT). After its re-discovery in adult humans ( 11 – 14 ), TAT gained considerable therapeutic interest for the treatment of metabolic disease ( 15 , 16 ). A profound understanding of TAT functions and heterogeneity is required to properly harness its benefits, hence, great focus has been devoted on investigating key cells, such as immune cells, that are critical contributors of TAT health.…”