Effect of a 24-Week Concurrent Exercise Intervention on Neck Adiposity and Its Distribution in Young Adults: The ACTIBATE Randomized Controlled Trial.

Neck adipose tissue (NAT) accumulation and neck circumference are independent predictors of cardiometabolic risk (CMR) and low-grade chronic inflammation in young adults. The present study examines whether a 24-week concurrent exercise intervention can reduce NAT volume and neck circumference in young adults, and whether any changes in these variables are related to changes in body composition, CMR, and the inflammatory profile. Seventy-four participants (51 women, age 22 ± 2 years) were included in the main analyses, after being randomly assigned to either a (a) control (n = 34), (b) moderate-intensity exercise (n = 19), or (c) vigorous-intensity exercise (n = 21) group. Participants in the exercise groups trained 3-4 days/week (endurance + resistance exercise training). NAT volume and NAT distribution across different depots were estimated using computed tomography before and after the intervention. Anthropometric variables, body composition (determined by dual-energy X-ray absorptiometry), and CMR/inflammatory markers were also recorded. The exercise intervention did not reduce the total NAT volume, nor was NAT distribution affected (p > .05). However, it did reduce neck circumference in the vigorous-intensity exercise group compared with the moderate-intensity exercise and control groups (by 0.8 and 1 cm, respectively, p ≤ .05). Changes in total NAT and neck circumference were positively, albeit weakly, related (adj. R2: .05-.21, all p ≤ .05) to changes in body weight and adiposity, leptin (only total NAT), and CMR (only neck circumference). Altogether 24 weeks of concurrent exercise does not appear to reduce NAT accumulation in young adults, but may slightly reduce neck circumference in those who partake in vigorous exercise.

Exercise-induced changes on exerkines that might influence brown adipose tissue metabolism in young sedentary adults.

ABSTRACTIn rodents, exercise alters the plasma concentration of exerkines that regulate white adipose tissue (WAT) browning or brown adipose tissue (BAT) metabolism. This study aims to analyse the acute and chronic effect of exercise on the circulating concentrations of 16 of these exerkines in humans. Ten young sedentary adults (6 female) performed a maximum walking effort test and a resistance exercise session. The plasma concentration of 16 exerkines was assessed before, and 3, 30, 60, and 120 min after exercise. Those exerkines modified by exercise were additionally measured in another 28 subjects (22 women). We also measured the plasma concentrations of the exerkines before and after a 24-week exercise programme (endurance + resistance; 3-groups: control, moderate-intensity and vigorous-intensity) in 110 subjects (75 women). Endurance exercise acutely increased the plasma concentration of lactate, norepinephrine, brain-derived neurotrophic factor, interleukin 6, and follistatin-like protein 1 (3 min after exercise), and musclin and fibroblast growth factor 21 (30 and 60 min after exercise), decreasing the plasma concentration of leptin (30 min after exercise). Adiponectin, atrial natriuretic peptide (ANP), ß-aminoisobutyric acid, meteorin-like, follistatin, pro-ANP, irisin and myostatin were not modified or not detectable. The resistance exercise session increased the plasma concentration of lactate 3 min after exercise. Chronic exercise did not alter the plasma concentration of these exerkines. In sedentary young adults, acute endurance exercise releases to the bloodstream exerkines that regulate BAT metabolism and WAT browning. In contrast, neither a low-volume resistance exercise session nor a 24-week training programme modified plasma levels of these molecules.HighlightsAcute endurance exercise increases the plasma concentration of lactate, norepinephrine, brain-derived neurotrophic factor, interleukin 6, follistatin-like protein 1, musclin, and fibroblast growth factor 21, and decrease the plasma concentration of leptin.The exercise-induced change in lactate plasma concentration is positively associated with brown adipose tissue volume, glucose uptake and radiodensity.Neither acute resistance exercise nor chronic exercise significantly alter the plasma concentration of these exerkines.Trial registration: ClinicalTrials.gov identifier: NCT02365129.

Acute and long-term exercise differently modulate plasma levels of oxylipins, endocannabinoids, and their analogues in young sedentary adults: A sub-study and secondary analyses from the ACTIBATE randomized controlled-trial.

BACKGROUND: Fatty acid-derived lipid mediators including oxylipins, endocannabinoids (eCBs), and their analogues, have emerged as key metabolites in the inflammatory and immune response to physiological stressors. METHODS: This report was based on a sub-study and secondary analyses the ACTIBATE single-center unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129). The study was performed in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada. Eligible participants were young, sedentary adults with no chronic diseases. Here, we performed both an acute endurance and resistance exercise sub-studies (n.ß=.ß14 and 17 respectively), and a 24-week supervised exercise intervention, combining endurance and resistance exercise training at moderate-intensity (MOD-EX) or vigorous-intensity (VIG-EX) exercise groups, in young sedentary adults. Randomization was performed by unrestricted randomization. Plasma levels of oxylipins, eCBs, and their analogues were measured using liquid chromatography-tandem mass spectrometry. FINDINGS: Both endurance and resistance exercise increased by.ß+50% the plasma levels of dihomo-..-linolenic acid and arachidonic acid (AA) omega-6 derived oxylipins, as well as eicosapentaenoic acid and docosahexaenoic acid omega-3 derived after 3 and 120.ßmin of the bout of exercise (all ..2.ß....ß0.219 and P.ß..±.ß0.039). These exercise modalities also increased the levels of anandamide and eCBs analogues (+25%). 145 young sedentary adults were assigned to a control (CON, n.ß=.ß54), a MOD-EX (n.ß=.ß48) or a VIG-EX (n.ß=.ß43). 102 participants were included in the final long-term analyses (CON, n.ß=.ß36; MOD-EX, n.ß=.ß33; and VIG-EX, n.ß=.ß33) of the trial. After 24-week of supervised exercise, MOD-EX decreased plasma levels of omega-6 oxylipins, concretely linoleic acid (LA) and adrenic acid derived oxylipins, and the eCBs analogues OEA and LEA in comparison to the CON (all P.ß..±.ß0.021). VIG-EX decreased LA-derived oxylipins and LEA compared to CON. No relevant adverse events were recorded. INTERPRETATION: Endurance and resistance exercises acutely increased plasma levels of oxylipins, eCBs, and their analogues, whereas 24 weeks of exercise training decreased fasting plasma levels of omega-6 oxylipins, and eCBs analogues in young, sedentary adults. FUNDING: See Acknowledgments section.

A larger brown fat volume and lower radiodensity are related to a greater cardiometabolic risk, especially in young men.

Objectives: Brown adipose tissue (BAT) is important in the maintenance of cardiometabolic health in rodents. Recent reports appear to suggest the same in humans, although if this is true remains elusive partly because of the methodological bias that affected previous research. This cross-sectional work reports the relationships of cold-induced BAT volume, activity (peak standardized uptake, SUVpeak), and mean radiodensity (an inverse proxy of the triacylglycerols content) with the cardiometabolic and inflammatory profile of 131 young adults, and how these relationships are influenced by sex and body weight. Design: This is a cross-sectional study. Methods: Subjects underwent personalized cold exposure for 2 h to activate BAT, followed by static 18F-fluorodeoxyglucose PET-CT scanning to determine BAT variables. Information on cardiometabolic risk (CMR) and inflammatory markers was gathered, and a CMR score and fatty liver index (FLI) were calculated. Results: In men, BAT volume was positively related to homocysteine and liver damage markers concentrations (independently of BMI and seasonality) and the FLI (all P ≤ 0.05). In men, BAT mean radiodensity was negatively related to the glucose and insulin concentrations, alanine aminotransferase activity, insulin resistance, total cholesterol/HDL-C, LDL-C/HDL-C, the CMR score, and the FLI (all P ≤ 0.02). In women, it was only negatively related to the FLI (P < 0.001). These associations were driven by the results for the overweight and obese subjects. No relationship was seen between BAT and inflammatory markers (P > 0.05). Conclusions: A larger BAT volume and a lower BAT mean radiodensity are related to a higher CMR, especially in young men, which may support that BAT acts as a compensatory organ in states of metabolic disruption.

No evidence of brown adipose tissue activation after 24 weeks of supervised exercise training in young sedentary adults in the ACTIBATE randomized controlled trial.

Exercise modulates both brown adipose tissue (BAT) metabolism and white adipose tissue (WAT) browning in murine models. Whether this is true in humans, however, has remained unknown. An unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129) was therefore conducted to study the effects of a 24-week supervised exercise intervention, combining endurance and resistance training, on BAT volume and activity (primary outcome). The study was carried out in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada (Spain). One hundred and forty-five young sedentary adults were assigned to either (i) a control group (no exercise, n = 54), (ii) a moderate intensity exercise group (MOD-EX, n = 48), or (iii) a vigorous intensity exercise group (VIG-EX n = 43) by unrestricted randomization. No relevant adverse events were recorded. 97 participants (34 men, 63 women) were included in the final analysis (Control; n = 35, MOD-EX; n = 31, and VIG-EX; n = 31). We observed no changes in BAT volume (Δ Control: -22.2 ± 52.6 ml; Δ MOD-EX: -15.5 ± 62.1 ml, Δ VIG-EX: -6.8 ± 66.4 ml; P = 0.771) or 18F-fluorodeoxyglucose uptake (SUVpeak Δ Control: -2.6 ± 3.1 ml; Δ MOD-EX: -1.2 ± 4.8, Δ VIG-EX: -2.2 ± 5.1; p = 0.476) in either the control or the exercise groups. Thus, we did not find any evidence of an exercise-induced change on BAT volume or activity in young sedentary adults.

Circulating concentrations of free triiodothyronine are associated with central adiposity and cardiometabolic risk factors in young euthyroid adults

Thyroid dysfunction is associated with classic cardiometabolic risk factors in humans. However, this relationship remains unclear in young euthyroid adults. The present work examines the associations of circulating thyroid hormones (THs) and thyroid-stimulating hormone (TSH) concentrations with body composition and cardiometabolic risk factors in young euthyroid adults. A total of 106 sedentary, euthyroid adults (72 women; 22 ± 2 years old) participated in this cross-sectional study. THs and TSH serum concentrations were determined in fasting conditions (6 h). Body composition (fat mass (FM), lean mass (LM), and visceral adipose tissue (VAT)) was determined by dual-energy X-ray absorptiometry, anthropometric parameters (weight, height, and waist circumference) were measured, and neck adipose tissue mass was quantified through computed tomography (CT) scanning. Cardiometabolic risk factors including fasting glucose and lipid metabolism markers, hepatic phosphatase and transaminases, and blood pressure were also assessed. Free triiodothyronine (FT3) concentration was positively associated with body mass index, LM, VAT, and waist circumference (all P ≤ 0.038). FT3 was also associated with glucose, insulin, HOMA-IR, fatty liver index, and blood pressure (all P < 0.024). All the associations were attenuated when adjusting for sex. In contrast, we found no associations of TSH or free thyroxine with any body composition parameter or cardiometabolic risk factors. In conclusion, FT3 is associated with central adiposity and cardiometabolic risk factors including insulin resistance, fatty liver index, and mean, systolic and diastolic blood pressure in young euthyroid adults. ClinicalTrials.gov identifier: NCT02365129. (AU)

Circulating concentrations of free triiodothyronine are associated with central adiposity and cardiometabolic risk factors in young euthyroid adults.

Thyroid dysfunction is associated with classic cardiometabolic risk factors in humans. However, this relationship remains unclear in young euthyroid adults. The present work examines the associations of circulating thyroid hormones (THs) and thyroid-stimulating hormone (TSH) concentrations with body composition and cardiometabolic risk factors in young euthyroid adults. A total of 106 sedentary, euthyroid adults (72 women; 22 ± 2 years old) participated in this cross-sectional study. THs and TSH serum concentrations were determined in fasting conditions (6 h). Body composition (fat mass (FM), lean mass (LM), and visceral adipose tissue (VAT)) was determined by dual-energy X-ray absorptiometry, anthropometric parameters (weight, height, and waist circumference) were measured, and neck adipose tissue mass was quantified through computed tomography (CT) scanning. Cardiometabolic risk factors including fasting glucose and lipid metabolism markers, hepatic phosphatase and transaminases, and blood pressure were also assessed. Free triiodothyronine (FT3) concentration was positively associated with body mass index, LM, VAT, and waist circumference (all P ≤ 0.038). FT3 was also associated with glucose, insulin, HOMA-IR, fatty liver index, and blood pressure (all P < 0.024). All the associations were attenuated when adjusting for sex. In contrast, we found no associations of TSH or free thyroxine with any body composition parameter or cardiometabolic risk factors. In conclusion, FT3 is associated with central adiposity and cardiometabolic risk factors including insulin resistance, fatty liver index, and mean, systolic and diastolic blood pressure in young euthyroid adults. ClinicalTrials.gov identifier: NCT02365129.

Diurnal variations of cold-induced thermogenesis in young, healthy adults: A randomized crossover trial.

BACKGROUND: Harnessing cold-induced thermogenesis (CIT) and brown adipose tissue (BAT) activity has been proposed as a means of counteracting a positive energy balance, and thus of combating obesity and its related comorbidities. However, it has remained unclear whether CIT and BAT activity show diurnal variation in humans - knowledge that might allow treatments based on these factors to be time-optimized. METHODS: A randomized crossover experiment was designed to examine whether CIT shows morning/evening variation in young, healthy adults (n = 14, 5 women). On the first experimental day, subjects' shivering thresholds were determined following a cooling protocol. After ≈96 h had elapsed, the subjects then returned on two further days (approx. 48 h apart) at 08:00 h or 18:00 in random order. On both the latter days, the resting energy expenditure (REE) was measured before the subjects underwent personalized cold exposure (i.e., according to their shivering threshold). CIT was then assessed for 60 min by indirect calorimetry. In an independent cross-sectional study (n = 133, 88 women), subjects came to the laboratory between 8:00 and 18:00 h and their BAT 18F-fluordeoxyglucose (18F-FDG) uptake was assessed after personalized cold stimulation. RESULTS: Both the REE and CIT were similar in the morning and evening (all P > 0.05). Indeed, 60 min of personalized-mild cold exposure in the morning or evening elicited a similar change in energy expenditure (16.8 ± 12.8 vs. 15.7 ± 15.1% increase above REE, P = 0.72). BAT 18F-FDG uptake was also similar in the morning, evening and afternoon (all P > 0.05). CONCLUSION: CIT does not appear to show morning/evening variation in young healthy adults, with the current study design and methodology. BAT 18F-FDG uptake appears not to change across the day either, although experiments with a within-subject study design are needed to confirm these findings. Registered under ClinicalTrials.gov Identifier no. NCT02365129.

Elevated plasma succinate levels are linked to higher cardiovascular disease risk factors in young adults.

BACKGROUND: Succinate is produced by both host and microbiota, with a key role in the interplay of immunity and metabolism and an emerging role as a biomarker for inflammatory and metabolic disorders in middle-aged adults. The relationship between plasma succinate levels and cardiovascular disease (CVD) risk in young adults is unknown. METHODS: Cross-sectional study in 100 (65% women) individuals aged 18-25 years from the ACTIvating Brown Adipose Tissue through Exercise (ACTIBATE) study cohort. CVD risk factors, body composition, dietary intake, basal metabolic rate, and cardiorespiratory fitness were assessed by routine methods. Plasma succinate was measured with an enzyme-based assay. Brown adipose tissue (BAT) was evaluated by positron emission tomography, and circulating oxylipins were assessed by targeted metabolomics. Fecal microbiota composition was analyzed in a sub-sample. RESULTS: Individuals with higher succinate levels had higher levels of visceral adipose tissue (VAT) mass (+ 42.5%), triglycerides (+ 63.9%), C-reactive protein (+ 124.2%), diastolic blood pressure (+ 5.5%), and pro-inflammatory omega-6 oxylipins than individuals with lower succinate levels. Succinate levels were also higher in metabolically unhealthy individuals than in healthy overweight/obese peers. Succinate levels were not associated with BAT volume or activity or with fecal microbiota composition and diversity. CONCLUSIONS: Plasma succinate levels are linked to a specific pro-inflammatory omega-6 signature pattern and higher VAT levels, and seem to reflect the cardiovascular status of young adults.

Thyroid function is not associated with brown adipose tissue volume and 18F-fluorodeoxyglucose uptake in young euthyroid adults.

PURPOSE: Thyroid hormones (THs) are important mediators of brown adipose tissue (BAT) differentiation. However, the association of TH concentrations with human BAT is unclear. The present work examines the associations between circulating thyroid-stimulating hormone (TSH) and THs concentrations (i.e. free triiodothyronine, FT3, and free thyroxine, FT4), under thermoneutral (22-23°C) and cold-induced conditions, and BAT volume, 18F-fluorodeoxyglucose (18F-FDG) uptake and mean radiodensity. METHODS: A total of 106 young healthy, euthyroid adults (34 men/72 women; 22.0 ± 2.1 years old; 24.9 ± 4.6 kg/m2) participated in this cross-sectional study. BAT volume, 18F-FDG uptake and mean radiodensity were assessed after 2 h of personalized (i.e. contemplating each individual's shivering threshold) cold exposure via positron emission tomography/computed tomography (PET/CT) static scanning. TSH and THs levels were determined before (thermoneutral) and 1 h after the cold exposure. RESULTS: Cold exposure increased circulating FT4 (P = 0.038) and reduced TSH levels (P ≤ 0.001). Conversely, the FT3 serum concentration was not modified by cold exposure (P = 0.435). No associations were found between the TSH and THs thermoneutral (all P > 0.111) or cold-induced levels (all P > 0.067) and BAT volume, 18F-FDG uptake and mean radiodensity. These findings were independent of sex and BMI. CONCLUSIONS: Thyroid function is modulated by cold exposure, yet it is not associated with BAT volume or glucose metabolism assessed after 2 h of cold exposure in young healthy, euthyroid adults.

Brown Adipose Tissue Volume and Fat Content Are Positively Associated With Whole-Body Adiposity in Young Men-Not in Women.

Human brown adipose tissue (BAT) volume has consistently been claimed to be inversely associated with whole-body adiposity. However, recent advances in the assessment of human BAT suggest that previously reported associations may have been biased. The present cross-sectional study investigates the association of BAT volume, mean radiodensity, and 18F-fluorodeoxyglucose (18F-FDG) uptake (assessed via a static positron emission tomography [PET]-computed tomography [CT] scan after a 2-h personalized cold exposure) with whole-body adiposity (measured by DXA) in 126 young adults (42 men and 84 women; mean ± SD BMI 24.9 ± 4.7 kg/m2). BAT volume, but not 18F-FDG uptake, was positively associated with BMI, fat mass, and visceral adipose tissue (VAT) mass in men but not in women. These associations were independent of the date when the PET-CT was performed, insulin sensitivity, and body surface area. BAT mean radiodensity, an inverse proxy of BAT fat content, was negatively associated with BMI, fat mass, and VAT mass in men and in women. These results refute the widely held belief that human BAT volume is reduced in obese persons, at least in young adults, and suggest that it might even be the opposite in young men.

Higher Physical Activity Is Related to Lower Neck Adiposity in Young Men, but to Higher Neck Adiposity in Young Women: An Exploratory Study.

The role of lifestyle behaviors on neck adipose tissue (NAT), a fat depot that appears to be involved in the pathogenesis of different cardiometabolic diseases and in inflammatory status, is unknown. In this cross-sectional and exploratory study, the authors examined the relationship between sedentary time and physical activity (PA) with neck adiposity in young adults. A total of 134 subjects (69% women, 23 ± 2 years) were enrolled. The time spent in sedentary behavior and PA of different intensity were objectively measured for 7 consecutive days (24 hr/day), using a wrist (nondominant)-worn accelerometer. The NAT volume was assessed using computed tomography, and the compartmental (subcutaneous, intermuscular, and perivertebral) and total NAT volumes were determined at the level of vertebra C5. Anthropometric indicators and body composition (by dual-energy X-ray absorptiometry) were determined. The time spent in light physical activity and moderate physical activity (MPA) and the overall PA were inversely associated with the intermuscular NAT volume in men, as were the MPA and overall PA with total NAT volume (all ps ≤ .04). Sedentary time was directly related to the total NAT volume (p = .04). An opposite trend was observed in women, finding a direct relationship of MPA with the subcutaneous NAT; of light physical activity, MPA, and overall PA with the perivertebral NAT; and of light physical activity with total NAT volumes (all ps ≤ .05). The observed associations were weak, and after adjusting for multiplicity, the results became nonsignificant (p > .05). These findings suggest that the specific characteristics of PA (time and intensity) might have sex-dependent implications in the accumulation of NAT.

Association between dietary factors and brown adipose tissue volume/18F-FDG uptake in young adults.

OBJECTIVE: To study the association between usual dietary factors (dietary energy density, nutrient intake, food group consumption, and dietary pattern) and brown adipose tissue (BAT) volume/18F-fluorodeoxyglucose (18F-FDG) uptake after personalized cold exposure in young healthy adults. METHODS: A total of 122 young adults (n = 82 women; 22.0 ± 2.1 years old; 24.8 ± 4.8 kg/m2) took part in this cross-sectional study. Dietary factors were measured via a food frequency questionnaire and three non-consecutive 24 h recalls. Dietary energy density (foods and caloric beverages included) and macronutrient intakes were subsequently estimated using EvalFINUT® software, food group consumption was estimated from the food frequency questionnaire, and different dietary patterns and quality indices were determined according to the reference methods. BAT volume, BAT 18F-FDG uptake, and skeletal muscle 18F-FDG uptake were assessed by static 18F-FDG positron-emission tomography and computed tomography (PET-CT) scans after a 2 h personalized exposure to cold. RESULTS: A direct association was detected between dietary energy density and BAT Standardized Uptake Value (SUV)mean (ß = 0.215; R2 = 0.044; P = 0.022), and between ethanol consumption and BAT volume (ß = 0.215; R2 = 0.044; P = 0.022). The a priori Mediterranean dietary pattern was inversely associated with BAT SUVmean and SUVpeak (ß = -0.273; R2 = 0.075; P = 0.003 and ß = -0.255; R2 = 0.066; P = 0.005 respectively). In addition, the diet quality index for a Mediterranean diet and a pro-inflammatory dietary pattern (as determined via the dietary inflammatory index) were directly associated with BAT SUVmean and SUVpeak (SUVmean: ß = 0.238; R2 = 0.053; P = 0.013 and ß = 0.256; R2 = 0.052; P = 0.012 respectively; SUVpeak: ß = 0.278; R2 = 0.073; P = 0.003 and ß = 0.248; R2 = 0.049; P = 0.016 respectively). After controlling for multiplicity and possible confounders (sex, the evaluation wave and BMI), all the detected associations persisted. CONCLUSION: Dietary factors are slightly associated with BAT volume and/or 18F-FDG uptake after a personalized cold exposure in young adults. Our results provide an overall picture of the potential relationships between dietary factors and BAT-related variables in humans.

Neck adipose tissue accumulation is associated with higher overall and central adiposity, a higher cardiometabolic risk, and a pro-inflammatory profile in young adults.

OBJECTIVES: Neck adipose tissue (NAT) volume increases with general adiposity, with fat accumulating in different neck tissue compartments. In patients with certain malignant/benign tumours, the accumulation of NAT, and certain NAT distributions, have been associated with cardiometabolic risk (CMR). However, it is unknown whether the same relationships exist in healthy people, and whether NAT accumulation and distribution are related to the inflammatory status. METHODS: In this cross-sectional study, 139 young healthy adults (68% women) underwent a computed tomography scan to quantify the volume of compartmental (i.e., subcutaneous, intermuscular and perivertebral) and total NAT at the height of vertebra C5. Anthropometric indicators were measured, and body composition determined using dual energy X-ray absorptiometry. Information on CMR factors (i.e., blood glycaemic and lipid markers, blood pressure and physical fitness) was also gathered, and a CMR score calculated. Several plasma cytokines and serum components of the innate immune system were measured to determine the inflammatory status. RESULTS: Compartmental and total NAT volumes were directly related to body mass index (BMI), and lean, fat, and visceral adipose tissue (VAT) masses (all, P ≤ 0.05). Larger compartmental (especially intermuscular) and total NAT volumes were directly associated with the CMR score, several CMR factors (i.e., glycaemic and lipid markers and blood pressure), and the C3, C4 and leptin concentrations. They were, however, inversely correlated with the CMR factors high density lipoprotein-cholesterol (HDL-C) and physical fitness, and with the adiponectin concentration (all P ≤ 0.05). Several of these associations remained statistically significant (P ≤ 0.05) after adjustment for BMI, body fat percentage or VAT mass. Overall, results did not change after applying false discovery rate correction. CONCLUSIONS: NAT volume and its distribution among different tissue compartments is associated with the CMR and inflammatory profile of young healthy adults. Total NAT volume appears to be as valuable as VAT mass in terms of predicting CMR and inflammatory status.

Distribution of Brown Adipose Tissue Radiodensity in Young Adults: Implications for Cold [18F]FDG-PET/CT Analyses.

PURPOSE: Nowadays, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET)/X-ray computed tomography (CT) is considered the best available technique to in vivo determination of human BAT volume. The most used Hounsfield unit (HU) threshold for BAT quantification is from - 250 to - 50 HU. Therefore, the main objective of the present study is (i) to examine the influence of SUV and HU thresholds on BAT quantification by [18F]FDG-PET/CT scan, (ii) to identify the proportion of BAT which is not detected by [18F]FDG-PET/CT scan when limiting the range between - 10 and - 50 HU, and (iii) to describe the distribution of BAT radiodensity by weight status and sex in young healthy individuals. PROCEDURES: We measured 125 individuals after a personalized cooling protocol with a static [18F]FDG-PET/CT scan. We quantified BAT using different combination of threshold in every single HU for all participants. RESULTS: We observed that the SUV threshold influences BAT quantification by [18F]FDG-PET/CT scans more than the HU range. We found that the range from - 50 to - 10 HU had the highest proportion of total BAT volume (43.2 %), which represents 41.4 % of the total BAT metabolic activity in our cohort. We also observed that BAT volume was not different between categories of body mass index, as well as BAT activity (SUVmean). In addition, BAT was less dense in women than in men, although the BAT activity (SUVmean) was higher in all ranges of HU. We also observed that the radiodensity of BAT located in the cervical area was mainly in the range from - 50 to - 10 HU. CONCLUSION: Therefore, all future human studies using static [18F]FDG-PET/CT scans should include BAT in the radiodensity range from - 50 to - 10 HU.

Brown adipose tissue volume and 18F-fluorodeoxyglucose uptake are not associated with energy intake in young human adults.

BACKGROUND: Several studies have explored the role of human brown adipose tissue (BAT) in energy expenditure. However, the link between BAT and appetite regulation needs to be more rigorously examined. OBJECTIVES: We aimed to investigate the associations of BAT volume and 18F-fluordeoxyglucose (18F-FDG) uptake after a personalized cold exposure with energy intake and appetite-related sensations in young healthy humans. METHODS: A total of 102 young adults (65 women; age: 22.08 ± 2.17 y; BMI: 25.05 ± 4.93 kg/m 2) took part in this cross-sectional study. BAT volume, BAT 18F-FDG uptake, and skeletal muscle 18F-FDG uptake were assessed by means of static 18F-FDG positron-emission tomography and computed tomography scans after a 2-h personalized exposure to cold. Energy intake was estimated via an objectively measured ad libitum meal and three nonconsecutive 24-h dietary recalls. Appetite-related sensations (i.e., hunger and fullness) were recorded by visual analog scales before and after a standardized breakfast (energy content = 50% of basal metabolic rate) and the ad libitum meal. Body composition was assessed by a whole-body DXA scan. RESULTS: BAT volume and 18F-FDG uptake were not associated with quantified ad libitum energy intake (all P > 0.088), nor with habitual energy intake estimated from the 24-h dietary recalls (all P  > 0.683). Lean mass was positively associated with both the energy intake from the ad libitum meal (ß: 17.612, R2 = 0.213; P < 0.001) and the habitual energy intake (ß: 16.052, R2 = 0.123; P = 0.001). Neither the interaction BAT volume × time elapsed after meal consumption nor that of BAT 18F-FDG uptake × time elapsed after meal consumption had any significant influence on appetite-related sensations after breakfast or after meal consumption (all P > 0.3). CONCLUSIONS: Neither BAT volume, nor BAT 18F-FDG uptake after cold stimulation, are related to appetite regulation in young adults. These results suggest BAT plays no important role in the regulation of energy intake in humans.This trial was registered at clinicaltrials.gov as NCT02365129.

Sleep duration and quality are not associated with brown adipose tissue volume or activity-as determined by 18F-FDG uptake, in young, sedentary adults.

STUDY OBJECTIVES: Short sleep duration and sleep disturbances have been related to obesity and metabolic disruption. However, the behavioral and physiological mechanisms linking sleep and alterations in energy balance and metabolism are incompletely understood. In rodents, sleep regulation is closely related to appropriate brown adipose tissue (BAT) thermogenic activity, but whether the same is true in humans has remained unknown. The present work examines whether sleep duration and quality are related to BAT volume and activity (measured by 18F-FDG) and BAT radiodensity in humans. METHODS: A total of 118 healthy adults (69% women, 21.9 ± 2.2 years, body mass index: 24.9 ± 4.7 kg/m2) participated in this cross-sectional study. Sleep duration and other sleep variables were measured using a wrist-worn accelerometer for seven consecutive days for 24 hours per day. The Pittsburgh Sleep Quality Index was used to assess sleep quality. All participants then underwent a personalized cold exposure to determine their BAT volume, activity, and radiodensity (a proxy of the intracellular triglyceride content), using static positron emission tomography combined with computed tomography (PET/CI) scan. RESULTS: Neither sleep duration nor quality was associated with BAT volume or activity (the latter represented by the mean and peak standardized 18F-FDG uptake values) or radiodensity (all p > .1). The lack of association remained after adjusting the analyses for sex, date of PET/CT, and body composition. CONCLUSIONS: Although experiments in rodent models indicate a strong relationship to exist between sleep regulation and BAT function, it seems that sleep duration and quality may not be directly related to the BAT variables examined in the present work. CLINICAL TRIAL REGISTRATION: NCT02365129 (ClinicalTrials.gov).

Relationship between the Daily Rhythm of Distal Skin Temperature and Brown Adipose Tissue 18F-FDG Uptake in Young Sedentary Adults.

The present study examines whether the daily rhythm of distal skin temperature (DST) is associated with brown adipose tissue (BAT) metabolism as determined by 18F-fluorodeoxyglucose (18F-FDG) uptake in young adults. Using a wireless thermometer (iButton) worn on the nondominant wrist, DST was measured in 77 subjects (26% male; age 22 ± 2 years; body mass index 25.2 ± 4.8 kg/m2) for 7 consecutive days. The temperatures to which they were habitually exposed over the day were also recorded. The interday stability of DST was calculated from the collected data, along with the intraday variability and relative amplitude; the mean temperature of the 5 and 10 consecutive hours with the maximum and minimum DST values, respectively; and when these hours occurred. Following exposure to cold, BAT volume and mean and peak standardized 18F-FDG uptake (SUVmean and SUVpeak) were determined for each subject via static 18F-FDG positron emission tomography/computed tomography scanning. Relative amplitude and the time at which the 10 consecutive hours of minimum DST values occurred were positively associated with BAT volume, SUVmean, and SUVpeak (p ≤ 0.02), whereas the mean DST of that period was inversely associated with the latter BAT variables (p ≤ 0.01). The interday stability and intraday variability of the DST were also associated (directly and inversely, respectively) with BAT SUVpeak (p ≤ 0.02 for both). All of these associations disappeared, however, when the analyses were adjusted for the ambient temperature to which the subjects were habitually exposed. Thus, the relationship between the daily rhythm of DST and BAT activity estimated by 18F-FDG uptake is masked by environmental and likely behavioral factors. Of note is that those participants exposed to the lowest ambient temperature showed 3 to 5 times more BAT volume and activity compared with subjects who were exposed to a warmer ambient temperature.

Supraclavicular skin temperature measured by iButtons and 18F-fluorodeoxyglucose uptake by brown adipose tissue in adults.

Currently, 18 [F]-Fluorodeoxyglucose (18F-FDG) in combination with a positron emission tomography/computed tomography (PET/CT) scan analysis is the most commonly used method to quantify human BAT volume and activity. However, this technique presents several drawbacks which negatively affect participant's health. The aim of the present work is to determine whether supraclavicular skin temperature can be used as an indirect marker of cold-induced BAT and skeletal muscle 18F-FDG uptake in adults, while taking into account body composition. We performed a personalized cooling protocol just before an 18F-FDG-PET/CT scan, and we measured supraclavicular skin temperature before (in warm conditions) and after the cooling protocol in 88 adults (n = 57 women, mean age: 21.9 ±â€¯2.1 years old, body mass index: 24.5 ±â€¯4.3 km/m2). We found that supraclavicular skin temperature at the warm and cold periods was weakly and positively associated with BAT activity (SUVmean and SUVpeak: ß = 3.000; R2 = 0.072; P = 0.022 and ß = 2.448; R2 = 0.060; P = 0.021), but not with skeletal muscle 18F-FDG uptake, after controlling for body composition. We performed further analyses and the positive associations persisted only in the group of women. In conclusion, supraclavicular skin temperature in warm and cold conditions seems to be related with cold-induced 18F-FDG uptake by BAT only in women, although the low explained variance of these associations means that there are other factors involved in the supraclavicular skin temperature.

Concurrent validity of supraclavicular skin temperature measured with iButtons and infrared thermography as a surrogate marker of brown adipose tissue.

Brown adipose tissue (BAT) thermogenic activity is commonly assessed with a positron emission tomography with computed tomography scan (PET/CT). This technique has several limitations and alternative techniques are needed. Supraclavicular skin temperature measured with iButtons and infrared thermography (IRT) has been proposed as an indirect marker of BAT activity. We studied the concurrent validity of skin temperature measured with iButtons vs. IRT and the association of supraclavicular skin temperature measured with iButtons and IRT with BAT. We measured skin temperature upon a shivering threshold test with iButtons and IRT in 6 different regions in 12 participants (n = 2 men). On a separate day, we determined supraclavicular skin temperature with an iButton and IRT after 2 h of a personalized cooling protocol. Thereafter, we quantified BAT volume and activity by PET/CT. We observed that the absolute differences between the devices were statistically different from 0 (all P < 0.05) after the shivering threshold test. Moreover, we did not find any association between supraclavicular skin temperature measured with iButtons or IRT and BAT 18F-FDG activity (r = -0.213; P = 0.530 and r = -0.079; P = 0.817). However, we observed a negative association of supraclavicular skin temperature measured by IRT with BAT 18F-FDG volume (r = -0.764; P = 0.006), but not with supraclavicular skin temperature measured with iButtons (r = -0.546; P = 0.082). In light of these results, we concluded that the measurement of skin temperature obtained by iButtons and IRT are not comparable. Furthermore, it seems that supraclavicular skin temperature is not associated with BAT 18F-FDG activity, but it appears to be negatively associated with BAT 18F-FDG volume in the case of IRT.