MRI characteristics of supraclavicular brown adipose tissue in relation to cold-induced thermogenesis in healthy human adults

Brown adipose tissue (BAT) has been proposed as a target to treat obesity and metabolic disease. Currently,; 18; F-Fluordeoxyglucose positron emission tomography (FDG-PET) is the standard for BAT-imaging. MRI might be a promising alternative, as it is not associated with ionizing radiation, offers a high resolution, and allows to discriminate different types of soft tissue.; We sought to evaluate whether supraclavicular BAT (scBAT) volume, fat-fraction (FF), and relaxation rate (R2*) determined by MRI can predict its metabolic activity, which was assessed by measurement of cold-induced thermogenesis (CIT).; Prospective cohort study.; Twenty healthy volunteers (9 female, 11 male), aged 18-47 years, with a body mass index (BMI) of 18-30 kg/m; 2; .; Multiecho gradient MRI for water-fat separation was used on a 3T device to measure the FF and T; 2; * of BAT.; Prior to imaging, CIT was determined by measuring the difference in energy expenditure (EE) during warm conditions and after cold exposure. Volume, FF, and R2* of scBAT was assessed and compared with CIT. In 11 participants, two MRI sessions with and without cold exposure were performed and the dynamic changes in FF and R2* assessed.; Linear regression was used to evaluate the relation of MRI measurements and CIT. P-values below 0.05 were considered significant; data are given as mean ± SD.; R2* correlated positively with CIT (r = 0.64, R; 2; = 0.41 P = 0.0041). Volume and FF did not correlate significantly with CIT. After mild cold exposure EE increased significantly (P = 0.0002), with a mean CIT of 147 kcal/day. The mean volume of scBAT was 72.4 ± 38.4 ml, mean FF was 74.3 ± 5.8%, and the mean R2* (1/T; 2; *) was 33.5 ± 12.7 s; -1; .; R2* of human scBAT can be used to estimate CIT. FF of scBAT was not associated with CI

Comparison of [; 18; F]FDG PET/CT with magnetic resonance imaging for the assessment of human brown adipose tissue activity

Brown adipose tissue (BAT) is a thermogenic tissue which can generate heat in response to mild cold exposure. As it constitutes a promising target in the fight against obesity, we need reliable techniques to quantify its activity in response to therapeutic interventions. The current standard for the quantification of BAT activity is [; 18; F]FDG PET/CT. Various sequences in magnetic resonance imaging (MRI), including those measuring its relative fat content (fat fraction), have been proposed and evaluated in small proof-of-principle studies, showing diverging results. Here, we systematically compare the predictive value of adipose tissue fat fraction measured by MRI to the results of [; 18; F]FDG PET/CT.; We analyzed the diagnostic reliability of MRI measured fat fraction (FF) for the estimation of human BAT activity in two cohorts of healthy volunteers participating in two prospective clinical trials (NCT03189511, NCT03269747). In both cohorts, BAT activity was stimulated by mild cold exposure. In cohort 1, we performed [; 18; F]FDG PET/MRI; in cohort 2, we used [; 18; F]FDG PET/CT followed by MRI. Fat fraction was determined by 2-point Dixon and 6-point Dixon measurement, respectively. Fat fraction values were compared to SUV; mean; in the corresponding tissue depot by simple linear regression.; In total, 33 male participants with a mean age of 23.9 years and a mean BMI of 22.8 kg/m; 2; were recruited. In 32 participants, active BAT was visible. On an intra-individual level, FF was significantly lower in high-SUV areas compared to low-SUV areas (cohort 1: p < 0.0001 and cohort 2: p = 0.0002). The FF of the supraclavicular adipose tissue depot was inversely related to its metabolic activity (SUVmean) in both cohorts (cohort 1: R; 2; = 0.18, p = 0.09 and cohort 2: R; 2; = 0.42, p = 0.009).; MRI FF explains only about 40% of the variation in BAT glucose uptake. Thus, it can currently not be used to substitute [; 18; F] FDG PET-based imaging for quantification of BAT activity.; ClinicalTrials.gov. NCT03189511 , registered on June 17, 2017, actual study start date was on May 31, 2017, retrospectively registered. NCT03269747 , registered on September 01, 2017

Effect of high-dose glucocorticoid treatment on human brown adipose tissue activity: a randomised, double-blinded, placebo-controlled cross-over trial in healthy men

Background Glucocorticoids (GCs) are widely applied anti-inflammatory drugs that are associated with adverse metabolic effects including insulin resistance and weight gain. Previous research indicates that GCs may negatively impact brown adipose tissue (BAT) activity in rodents and humans.Methods We performed a randomised, double-blinded cross-over trial in 16 healthy men (clinicaltrials.gov NCT03269747). Participants received 40 mg of prednisone per day for one week or placebo. After a washout period of four weeks, participants crossed-over to the other treatment arm. Primary endpoint was the increase in resting energy expenditure (EE) in response to a mild-cold stimulus (cold-induced thermogenesis, CIT). Secondary outcomes comprised mean 18F-FDG uptake into supraclavicular BAT (SUVmean) as determined by FDG-PET/CT, volume of the BAT depot as well as fat content determined by MRI. The plasma metabolome and the transcriptome of supraclavicular BAT and of skeletal muscle biopsies after each treatment period were analysed.Findings Sixteen participants were recruited to the trial and completed it successfully per protocol. After prednisone treatment resting EE was higher both during warm and cold conditions. However, CIT was similar, 153 kcal/24 h (95% CI 40-266 kcal/24 h) after placebo and 186 kcal/24 h (95% CI 94-277 kcal/24 h, p = 0.38) after prednisone. SUVmean of BAT after cold exposure was not significantly affected by prednisone (3.36 g/ml, 95% CI 2.69-4.02 g/ml, vs 3.07 g/ml, 95% CI 2.52-3.62 g/ml, p = 0.28). Results of plasma metabolomics and BAT transcriptomics corroborated these findings. RNA sequencing of muscle biopsies revealed higher expression of genes involved in calcium cycling. No serious adverse events were reported and adverse events were evenly distributed between the two treatments.Interpretation Prednisone increased EE in healthy men possibly by altering skeletal muscle calcium cycling. Cold induced BAT activity was not affected by GC treatment, which indicates that the unfavourable metabolic effects of GCs are independent from thermogenic adipocytes.ISSN:2352-396