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Effects of Capsinoid Intake on Brown Adipose Tissue Vascular Density and Resting Energy Expenditure in Healthy, Middle-Aged Adults: A Randomized, Double-Blind, Placebo-Controlled Study.
Fuse, S, Endo, T, Tanaka, R, Kuroiwa, M, Ando, A, Kume, A, Yamamoto, A, Kuribayashi, K, Somekawa, S, Takeshita, M, et al
Nutrients. 2020;(9)
Abstract
Capsinoids are some of the most promising ingredients to increase energy expenditure (EE) due to brown adipose tissue (BAT) activation. However, there is limited information regarding the effect of prolonged capsinoid ingestion (CI) on BAT activity and resting EE (REE) in healthy, middle-aged, normal to overweight subjects (Subhealthy) with distinct BAT characteristics. We examined the changes in BAT density (BAT-d), using near-infrared time-resolved spectroscopy, and REE/kg induced by daily CI. Forty Subhealthy [age, 43.8 (mean) years; BMI, 25.4 kg/m2] received either capsinoid (9 mg/day) or a placebo daily for 6 weeks in a double-blind design. Total hemoglobin concentration in the supraclavicular region ([total-Hb]sup), an indicator of BAT-d, and REE/kg were measured. The changes in post-intervention [total-Hb]sup were greater in the capsinoid group (CA-G) than in the placebo group (PL-G) [5.8 µM (+12.4%) versus 1.0 µM (+2.1%); p = 0.017]. There was a significant relationship between BAT-d and REE/kg; however, post-supplementation REE/kg was not significantly different between the two groups (p = 0.228). In the overweight subgroup, changes in REE/kg were greater in the CA-G than in the PL-G [0.6 cal/kg/min (+4.3%) versus -0.3 cal/kg/min (-2.1%); p = 0.021]. CI enhanced [total-Hb]sup, a reflection of BAT-d, showing a good correlation with REE in Subhealthy.
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Relationship between the Daily Rhythm of Distal Skin Temperature and Brown Adipose Tissue 18F-FDG Uptake in Young Sedentary Adults.
Acosta, FM, Martinez-Tellez, B, Blondin, DP, Haman, F, Rensen, PCN, Llamas-Elvira, JM, Martinez-Nicolas, A, Ruiz, JR
Journal of biological rhythms. 2019;(5):533-550
Abstract
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.
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A new method of infrared thermography for quantification of brown adipose tissue activation in healthy adults (TACTICAL): a randomized trial.
Ang, QY, Goh, HJ, Cao, Y, Li, Y, Chan, SP, Swain, JL, Henry, CJ, Leow, MK
The journal of physiological sciences : JPS. 2017;(3):395-406
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Abstract
The ability to alter the amount and activity of brown adipose tissue (BAT) in human adults is a potential strategy to manage obesity and related metabolic disorders associated with food, drug, and environmental stimuli with BAT activating/recruiting capacity. Infrared thermography (IRT) provides a non-invasive and inexpensive alternative to the current methods (e.g. 18F-FDG PET) used to assess BAT. We have quantified BAT activation in the cervical-supraclavicular (C-SCV) region using IRT video imaging and a novel image computational algorithm by studying C-SCV heat production in healthy young men after cold stimulation and the ingestion of capsinoids in a prospective double-blind placebo-controlled randomized trial. Subjects were divided into low-BAT and high-BAT groups based on changes in IR emissions in the C-SCV region induced by cold. The high-BAT group showed significant increases in energy expenditure, fat oxidation, and heat output in the C-SCV region post-capsinoid ingestion compared to post-placebo ingestion, but the low-BAT group did not. Based on these results, we conclude that IRT is a promising tool for quantifying BAT activity.
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Tea catechin and caffeine activate brown adipose tissue and increase cold-induced thermogenic capacity in humans.
Yoneshiro, T, Matsushita, M, Hibi, M, Tone, H, Takeshita, M, Yasunaga, K, Katsuragi, Y, Kameya, T, Sugie, H, Saito, M
The American journal of clinical nutrition. 2017;(4):873-881
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Abstract
Background: The thermogenic effects of green tea catechin have been repeatedly reported, but their mechanisms are poorly understood.Objective: The aim of this study was to investigate the acute and chronic effects of catechin on brown adipose tissue (BAT), a site specialized for nonshivering thermogenesis, in humans.Design: Fifteen healthy male volunteers underwent fluorodeoxyglucose-positron emission tomography to assess BAT activity. To examine the acute catechin effect, whole-body energy expenditure (EE) after a single oral ingestion of a beverage containing 615 mg catechin and 77 mg caffeine (catechin beverage) was measured. Next, to investigate the chronic catechin effects, 10 men with low BAT activity were enrolled. Before and after ingestion of the catechin beverage 2 times/d for 5 wk, cold-induced thermogenesis (CIT) after 2 h of cold exposure at 19°C, which is proportional to BAT activity, was examined. Both the acute and chronic trials were single-blinded, randomized, placebo-controlled, season-matched crossover studies.Results: A single ingestion of the catechin beverage increased EE in 9 subjects who had metabolically active BAT (mean ± SEM: +15.24 ± 1.48 kcal, P < 0.01) but not in 6 subjects who had negligible activities (mean ± SEM: +3.42 ± 2.68 kcal). The ingestion of a placebo beverage containing 82 mg caffeine produced a smaller and comparative EE response in the 2 subject groups. Multivariate regression analysis revealed a significant interaction between BAT and catechin on EE (β = 0.496, P = 0.003). Daily ingestion of the catechin beverage elevated mean ± SEM CIT (from 92.0 ± 26.5 to 197.9 ± 27.7 kcal/d; P = 0.009), whereas the placebo beverage did not change it.Conclusion: Orally ingested tea catechin with caffeine acutely increases EE associated with increased BAT activity and chronically elevates nonshivering CIT, probably because of the recruitment of BAT, in humans. These trials were registered at www.umin.ac.jp/ctr/ as UMIN000016361.
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Preparation methods prior to PET/CT scanning that decrease uptake of 18F-FDG by myocardium, brown adipose tissue, and skeletal muscle.
Shao, D, Tian, XW, Gao, Q, Liang, CH, Wang, SX
Acta radiologica (Stockholm, Sweden : 1987). 2017;(1):10-18
Abstract
BACKGROUND The hypermetabolic environment of the myocardium, brown adipose tissue (BAT), and muscle will have an effect on the diagnostic accuracy of 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT). A low carbohydrate, high fat, and protein-permitted diet before PET/CT scanning can reduce the degree of 18F-FDG uptake by the myocardium, brown adipose tissue, and skeletal muscle. PURPOSE To determine the effect of a low carbohydrate, high fat and protein-permitted diet on 18F-FDG uptake by myocardium, BAT, and muscle during PET/CT. MATERIAL AND METHODS A total of 126 patients who adhered to two meals before PET/CT scanning (that were prepared using a low carbohydrate, high fat, and protein-permitted diet), i.e. the diet group, were compared with 126 patients who fasted for at least 12 h prior to scanning (i.e. the fasting group). The degree of 18F-FDG uptake within the myocardium, BAT, and muscle were stratified into four grades (range, 0-3) with 0 for negligible uptake, and 3 for intense uptake. Correlations between the diet and fasting groups with respect to degree of 18F-FDG uptake within the myocardium, BAT, and muscle were analyzed. RESULTS The degree of 18F-FDG uptake within the myocardium, BAT, and muscle in the diet group was significantly lower compared with the 18F-FDG uptake within myocardium, BAT, and muscle in the fasting group (P < 0.001, P = 0.001, P < 0.001). CONCLUSION A low carbohydrate/high fat diet before 18F-FDG injection can suppress uptake of 18F-FDG within the myocardium, BAT, and skeletal muscle.
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Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance.
Hanssen, MJ, Wierts, R, Hoeks, J, Gemmink, A, Brans, B, Mottaghy, FM, Schrauwen, P, van Marken Lichtenbelt, WD
Diabetologia. 2015;(3):586-95
Abstract
AIMS/HYPOTHESIS Human brown adipose tissue (BAT) has recently emerged as a potential target in the treatment of type 2 diabetes, owing to its capacity to actively clear glucose from the circulation—at least upon cold exposure. The effects of insulin resistance on the capacity of human BAT to take up glucose are unknown. Prolonged fasting is known to induce insulin resistance in peripheral tissues in order to spare glucose for the brain. METHODS We studied the effect of fasting-induced insulin resistance on the capacity of BAT to take up glucose during cold exposure as well as on cold-stimulated thermogenesis. BAT glucose uptake was assessed by means of cold-stimulated dynamic 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography/computed tomography ([(18)F]FDG-PET/CT) imaging. RESULTS We show that a 54 h fasting period markedly decreases both cold-induced BAT glucose uptake and nonshivering thermogenesis (NST) during cold stimulation. In vivo molecular imaging and modelling revealed that the reduction of glucose uptake in BAT was due to impaired cellular glucose uptake and not due to decreased supply. Interestingly, decreased BAT glucose uptake upon fasting was related to a decrease in core temperature during cold exposure, pointing towards a role for BAT in maintaining normothermia in humans. CONCLUSIONS/INTERPRETATION Cold-stimulated glucose uptake in BAT is strongly reduced upon prolonged fasting. When cold-stimulated glucose uptake in BAT is also reduced under other insulin-resistant states, such as diabetes, cold-induced activation of BAT may not be a valid way to improve glucose clearance by BAT under such conditions. TRIAL REGISTRATION www.trialregister.nl NTR3523 FUNDING This work was supported by the EU FP7 project DIABAT (HEALTH-F2-2011-278373 to WDvML) and by the Netherlands Organization for Scientific Research (TOP 91209037 to WDvML).
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Activating brown adipose tissue through exercise (ACTIBATE) in young adults: Rationale, design and methodology.
Sanchez-Delgado, G, Martinez-Tellez, B, Olza, J, Aguilera, CM, Labayen, I, Ortega, FB, Chillon, P, Fernandez-Reguera, C, Alcantara, JMA, Martinez-Avila, WD, et al
Contemporary clinical trials. 2015;(Pt B):416-425
Abstract
AIMS: The energy expenditure capacity of brown adipose tissue (BAT) makes it an attractive target as a therapy against obesity and type 2 diabetes. BAT activators namely catecholamines, natriuretic peptides and certain myokines, are secreted in response to exercise. ACTIBATE will determine the effect of exercise on BAT activity and mass measured by positron emission tomography/computed tomography (PET/CT, primary outcome) in young adults. ACTIBATE will also investigate the physiological consequences of activating BAT (secondary outcomes). METHODS ACTIBATE will recruit 150 sedentary, healthy, young adults (50% women) aged 18-25 years. Eligible participants will be randomly assigned to a non-exercise group (n ≈ 50) or one of two exercise groups (n=50 each). Participants in the exercise groups will perform aerobic and strength training 3-4 days/week at a heart rate equivalent to 60% of heart rate reserve (HRres), and at 50% of 1 repetition maximum (RM) for the moderate-intensity group, and at 80% of HRres and 70% RM for the vigorous-intensity group. Laboratory measures completed at baseline and 6 months include BAT activity and mass, resting energy expenditure, meal and cold-induced thermogenesis, body temperature regulation and shivering threshold, body composition and cardiovascular disease risk factors. We will also obtain biopsies from abdominal subcutaneous white adipose tissue and skeletal muscle to analyse the expression of genes encoding proteins involved in the thermogenic machinery. DISCUSSION Findings from ACTIBATE will have significant implications for our understanding of exercise and its protective effects against the development of type 2 diabetes, obesity and related metabolic diseases. ClinicalTrials.gov ID: NCT02365129.
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Aged garlic extract with supplement is associated with increase in brown adipose, decrease in white adipose tissue and predict lack of progression in coronary atherosclerosis.
Ahmadi, N, Nabavi, V, Hajsadeghi, F, Zeb, I, Flores, F, Ebrahimi, R, Budoff, M
International journal of cardiology. 2013;(3):2310-4
Abstract
BACKGROUND Aged garlic extract with supplement (AGE-S) significantly reduces coronary artery calcium (CAC). We evaluated the effects of AGE-S on change in white (wEAT) and brown (bEAT) epicardial adipose tissue, homocysteine and CAC. METHODS Sixty subjects, randomized to a daily capsule of placebo vs. AGE-S inclusive of aged garlic-extract (250 mg) plus vitamin-B12 (100 μg), folic-acid (300 μg), vitamin-B6 (12.5mg) and L-arginine (100mg) underwent CAC, wEAT and bEAT measurements at baseline and 12 months. The postcuff deflation temperature-rebound index of vascular function was assessed using a reactive-hyperemia procedure. Vascular dysfunction was defined according to the tertiles of temperature-rebound at 1 year of follow-up. CAC progression was defined as an annual-increase in CAC>15%. RESULTS From baseline to 12 months, there was a strong correlation between increase in wEAT and CAC (r(2)=0.54, p=0.0001). At 1 year, the risks of CAC progression and increased wEAT and homocysteine were significantly lower in AGE-S to placebo (p<0.05). Similarly, bEAT and temperature-rebound were significantly higher in AGE-S as compared to placebo (p<0.05). Strong association between increase in temperature-rebound and bEAT/wEAT ratio (r(2)=0.80, p=0.001) was noted, which was more robust in AGE-S. Maximum beneficial effect of AGE-S was noted with increase in bEAT/wEAT ratio, temperature-rebound, and lack of progression of homocysteine and CAC. CONCLUSIONS AGE-S is associated with increase in bEAT/wEAT ratio, reduction of homocysteine and lack of progression of CAC. Increases in bEAT/wEAT ratio correlated strongly with increases in vascular function measured by temperature-rebound and predicted a lack of CAC progression and plaque stabilization in response to AGE-S.
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Nonpungent capsaicin analogs (capsinoids) increase energy expenditure through the activation of brown adipose tissue in humans.
Yoneshiro, T, Aita, S, Kawai, Y, Iwanaga, T, Saito, M
The American journal of clinical nutrition. 2012;(4):845-50
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BACKGROUND Capsinoids-nonpungent capsaicin analogs-are known to activate brown adipose tissue (BAT) thermogenesis and whole-body energy expenditure (EE) in small rodents. BAT activity can be assessed by [¹⁸F]fluorodeoxyglucose-positron emission tomography (FDG-PET) in humans. OBJECTIVES The aims of the current study were to examine the acute effects of capsinoid ingestion on EE and to analyze its relation to BAT activity in humans. DESIGN Eighteen healthy men aged 20-32 y underwent FDG-PET after 2 h of cold exposure (19°C) while wearing light clothing. Whole-body EE and skin temperature, after oral ingestion of capsinoids (9 mg), were measured for 2 h under warm conditions (27°C) in a single-blind, randomized, placebo-controlled, crossover design. RESULTS When exposed to cold, 10 subjects showed marked FDG uptake into adipose tissue of the supraclavicular and paraspinal regions (BAT-positive group), whereas the remaining 8 subjects (BAT-negative group) showed no detectable uptake. Under warm conditions (27°C), the mean (±SEM) resting EE was 6114 ± 226 kJ/d in the BAT-positive group and 6307 ± 156 kJ/d in the BAT-negative group (NS). EE increased by 15.2 ± 2.6 kJ/h in 1 h in the BAT-positive group and by 1.7 ± 3.8 kJ/h in the BAT-negative group after oral ingestion of capsinoids (P < 0.01). Placebo ingestion produced no significant change in either group. Neither capsinoids nor placebo changed the skin temperature in various regions, including regions close to BAT deposits. CONCLUSION Capsinoid ingestion increases EE through the activation of BAT in humans. This trial was registered at http://www.umin.ac.jp/ctr/ as UMIN 000006073.