Brown adipose tissue (BAT) burns fat to produce heat when the body is exposed to cold and plays a role in energy metabolism. Using fluorodeoxyglucose-positron emission tomography and computed tomography, we previously reported that BAT decreases with age and thereby accelerates age-related accumulation of body fat in humans. Thus, the recruitment of BAT may be effective for body fat reduction. In this study, we examined the effects of repeated stimulation by cold and capsinoids (nonpungent capsaicin analogs) in healthy human subjects with low BAT activity. Acute cold exposure at 19°C for 2 hours increased energy expenditure (EE). Cold-induced increments of EE (CIT) strongly correlated with BAT activity independently of age and fat-free mass. Daily 2-hour cold exposure at 17°C for 6 weeks resulted in a parallel increase in BAT activity and CIT and a concomitant decrease in body fat mass. Changes in BAT activity and body fat mass were negatively correlated. Similarly, daily ingestion of capsinoids for 6 weeks increased CIT. These results demonstrate that human BAT can be recruited even in individuals with decreased BAT activity, thereby contributing to body fat reduction.

Brown adipose tissue (BAT) can be identified by 18 F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) combined with X-ray computed tomography (CT) in adult humans. The objective of this study was to clarify the relationship between BAT and adiposity in healthy adult humans, particularly to test the idea that decreased BAT activity may be associated with body fat accumulation with age. One hundred and sixty-two healthy volunteers aged 20-73 years (103 males and 59 females) underwent FDG-PET/CT after 2-h cold exposure at 19 °C with light clothing. Cold-activated BAT was detected in 41% of the subjects (BAT-positive). Compared with the BAT-negative group, the BAT-positive group was younger (P < 0.01) and showed a lower BMI (P < 0.01), body fat content (P < 0.01), and abdominal fat (P < 0.01). The incidence of cold-activated BAT decreased with age (P < 0.01), being more than 50% in the twenties, but less than 10% in the fifties and sixties. The adiposity-related parameters showed some sex differences, but increased with age in the BAT-negative group (P < 0.01), while they remained unchanged from the twenties to forties in the BAT-positive group, in both sexes. These results suggest that decreased BAT activity may be associated with accumulation of body fat with age.

Brown adipose tissue (BAT) can be identified by 18F‐fluorodeoxyglucose (FDG)‐positron emission tomography (PET) in adult humans. Thirteen healthy male volunteers aged 20–28 years underwent FDG‐PET after 2‐h cold exposure at 19 °C with light‐clothing and intermittently putting their legs on an ice block. When exposed to cold, 6 out of the 13 subjects showed marked FDG uptake into adipose tissue of the supraclavicular and paraspinal regions (BAT‐positive group), whereas the remaining seven showed no detectable uptake (BAT‐negative group). The BMI and body fat content were similar in the two groups. Under warm conditions at 27 °C, the energy expenditure of the BAT‐positive group estimated by indirect calorimetry was 1,446 ± 97 kcal/day, being comparable with that of the BAT‐negative group (1,434 ± 246 kcal/day). After cold exposure, the energy expenditure increased markedly by 410 ± 293 (P < 0.05) and slightly by 42 ± 114 kcal/day (P = 0.37) in the BAT‐positive and ‐negative groups, respectively. A positive correlation (P < 0.05) was found between the cold‐induced rise in energy expenditure and the BAT activity quantified from FDG uptake. After cold exposure, the skin temperature in the supraclavicular region close to BAT deposits dropped by 0.14 °C in the BAT‐positive group, whereas it dropped more markedly (P < 0.01) by 0.60 °C in the BAT‐negative group. The skin temperature drop in other regions apart from BAT deposits was similar in the two groups. These results suggest that BAT is involved in cold‐induced increases in whole‐body energy expenditure, and, thereby, the control of body temperature and adiposity in adult humans.

BAT, independent of age, sex and body fatness, has a significant impact on glucose metabolism in adult healthy humans.

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.

Brown adipose tissue (BAT) is responsible for cold-and diet-induced thermogenesis, and thereby contributes to the control of whole-body energy expenditure (EE) and body fat content. BAT activity can be assessed by fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET) in human subjects. Grains of paradise (GP, Aframomum melegueta), a species of the ginger family, contain pungent, aromatic ketones such as 6-paradol, 6-gingerol and 6-shogaol. An alcohol extract of GP seeds and 6-paradol are known to activate BAT thermogenesis in small rodents. The present study aimed to examine the effects of the GP extract on whole-body EE and to analyse its relation to BAT activity in men. A total of nineteen healthy male volunteers aged 20-32 years underwent FDG-PET after 2 h of exposure to cold at 198C with light clothing. A total of twelve subjects showed marked FDG uptake into the adipose tissue of the supraclavicular and paraspinal regions (BAT positive). The remaining seven showed no detectable uptake (BAT negative). Within 4 weeks after the FDG-PET examination, whole-body EE was measured at 278C before and after oral ingestion of GP extract (40 mg) in a single-blind, randomised, placebocontrolled, crossover design. The resting EE of the BAT-positive group did not differ from that of the BAT-negative group. After GP extract ingestion, the EE of the BAT-positive group increased within 2 h to a significantly greater (P,0·01) level than that of the BAT-negative group. Placebo ingestion produced no significant change in EE. These results suggest that oral ingestion of GP extract increases wholebody EE through the activation of BAT in human subjects.Key words: Grains of paradise: 6-Paradol: Brown adipose tissue: Energy expenditure Brown adipose tissue (BAT) is the major site for sympathetically activated thermogenesis during cold exposure and spontaneous overfeeding, at least in small rodents (1) . Recent studies using fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET) combined with computed tomography (CT) have revealed the existence of metabolically active BAT in adult human subjects (2 -4) . It is now established that, in healthy adults, BAT is activated by acute cold exposure and significantly contributes to cold-induced thermogenesis (2 -5) . It has also been demonstrated that the prevalence and activity of BAT are lower in subjects with higher adiposity, being negatively correlated with BMI, body fat content and visceral fat (2,3) . Moreover we found that the prevalence of BAT decreased with age, being more than 50 % in the twenties, but less than 10 % in the fifties and sixties, and that decreased BAT activity is associated with age-related accumulation of body fat (6) . It is thus likely that BAT, based on its thermogenic activity, contributes to the control of whole-body energy expenditure (EE) and body fat metabolism in human subjects, as established in small rodents, and thereby is a promising target for interventions to prevent and treat obesity. A number of food ingredients have been p...

BACKGROUND: Brown adipose tissue (BAT) is involved in the regulation of whole-body energy expenditure and adiposity. The activity and prevalence of BAT decrease with age in humans. OBJECTIVE: To examine the effects of single nucleotide polymorphisms of the genes for uncoupling protein 1 (UCP1) and b3-adrenergic receptor (b3AR), key molecules of BAT thermogenesis, on age-related decline of BAT activity and accumulation of body fat in humans. METHODS: One hundred ninety-nine healthy volunteers (20-72 years old (y.o.)) underwent fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) after 2-h cold exposure to assess BAT activity. The visceral and subcutaneous fat areas at the abdominal level were estimated from the CT images. They were genotyped for À 3826 A/G polymorphism of the UCP1 gene and 64 Trp/Arg mutation of the b3AR gene. RESULTS: BAT was detected in 88 subjects out of 199 (44%), more in younger (p30 y.o., 55%) than older subjects (440 y.o., 15%). BAT prevalence of older subjects tended to be lower in the UCP1 G/G group than the A allele group (A/A and A/G), and also in the b3AR Arg allele group (Trp/Arg and Arg/Arg) than the Trp/Trp group. When compared subjects who had two or more base substitutions on the two genes (the 2-4 allele group) with those who had less than two base substitutions (the 0-1 allele group), BAT prevalence was comparable in younger subjects (62% vs 50%) but lower in older subjects (0% vs 24%, Po0.05). Visceral fat area of the 2-4 allele group was higher than that of the 0-1 allele group (Po0.05) in older subjects, but not in younger subjects. CONCLUSION: UCP1 À 3826 A/G and b3AR 64 Trp/Arg substitutions accelerate age-related decrease in BAT activity, and thereby may associate with visceral fat accumulation with age.

Summary Kaempferia parvifl ora extract (KP) has been reported to have a preventive effect on obesity in mice, probably by increasing energy expenditure (EE). The aims of the current study were to examine the acute effects of KP ingestion on whole-body EE in humans and to analyze its relation to the activity of brown adipose tissue (BAT), a site of non-shivering thermogenesis. After an oral ingestion of an ethanol extract of KP, EE increased signifi cantly, showing a maximal increase of 229Ϯ69 kJ/d at 60 min, while it did not change after placebo ingestion. To evaluate BAT activity, the subjects underwent fl uorodeoxyglucose-positron emission tomography, and divided into two groups with high-and low-BAT activities. A similar and greater response of EE to KP ingestion was observed in the high-BAT group (351Ϯ50 kJ/d at 60 min), but not in the low activity group. Placebo ingestion did not cause any signifi cant EE change in either group. These results indicate that a single oral ingestion of the KP extract can potentially increase whole-body EE probably through the activation of BAT in healthy men, and may be useful as an anti-obesity regimen.