Brown fat-associated postprandial thermogenesis in humans: Different effects of isocaloric meals rich in carbohydrate, fat, and protein.

The increase of whole-body energy expenditure seen after a single meal ingestion, referred to as diet-induced thermogenesis (DIT), substantially varies depending on the meal's macronutrient composition. Brown adipose tissue (BAT), a site of non-shivering thermogenesis, was reported to be involved in DIT. To examine the effects of meal composition on BAT-associated DIT in humans, healthy male participants underwent fluorodeoxyglucose-positron emission tomography to assess BAT activity, and respiratory gas analysis for 2 h after ingestion of a carbohydrate-, protein-, or fat-rich meal (C-meal, P-meal, and F-meal, respectively). The calculated DIT at 2 h was 6.44 ± 2.01%, 3.49 ± 2.00%, and 2.32 ± 0.90% of the ingested energy after the P-meal, C-meal, and F-meal, respectively. The DIT after C-meal ingestion correlated positively with BAT activity (P = 0.011), and was approximately twice greater in the group with high-BAT activity than in the group with low-BAT activity (4.35 ± 1.74% vs. 2.12 ± 1.76%, P < 0.035). Conversely, the DIT after F-meal or P-meal ingestion did not correlate with BAT activity, with no difference between the two groups. Thus, BAT has a significant role in DIT after ingestion of a carbohydrate-rich meal, but hardly after ingestion either protein- or fat-rich meal.

Prolonged Treatment with Grains of Paradise (Aframomum melegueta) Extract Recruits Adaptive Thermogenesis and Reduces Body Fat in Humans with Low Brown Fat Activity.

Increasing adaptive thermogenesis through the activation of brown adipose tissue (BAT) is a promising practical strategy for preventing obesity and related disorders. Ingestion of a single dose of 40 mg of an extract of Grains of Paradise (GP), a ginger family species, reportedly triggers BAT thermogenesis in individuals with high but not in those with low BAT activity. We hypothesized that prolonged treatment with GP might revive BAT in individuals who have lost active BAT. In the present study, we recruited 9 healthy young male volunteers with reduced BAT that was assessed by fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) following 2-h cold exposure at 19ºC. The subjects ingested GP extract (40 mg/d) or placebo every day for 5 wk. Before and after the treatment with either GP or placebo, their body composition and BAT-dependent cold-induced thermogenesis (CIT)-a non-invasive index of BAT-were measured in a single-blinded, randomized, placebo-controlled cross-over design. Their whole-body resting energy expenditure at a thermoneutral condition remained unchanged following GP treatment. However, CIT after treatment was significantly higher in GP-treated individuals than in placebo-treated individuals. Body weight and fat-free mass did not change significantly following GP or placebo treatment. Notably, body fat percentage slightly but significantly decreased after GP treatment but not after placebo treatment. These results suggest that repeated ingestion of GP elevates adaptive thermogenesis through the re-activation of BAT, thereby reducing body fat in individuals with low BAT activity.

Evaluation of Brown Adipose Tissue Using Near-Infrared Time-Resolved Spectroscopy.

Human brown adipose tissue (BAT) activity (SUVmax) has been typically evaluated by 18F-fluorodeoxy glucose (FDG)-positron emission tomography (PET) combined with computed tomography (CT). In this study, the objective was to detect human BAT by near-infrared time-resolved spectroscopy (NIRTRS), a noninvasive and simple method for measuring total hemoglobin concentration [total-Hb] and reduced scattering coefficient (µs') in the tissue. The [total-Hb] in the supraclavicular region of the BAT (+) (SUVmax≥2.0) group was 95.0±28.2 µM (mean+/-SD), which was significantly higher than that of the BAT (-) (SUVmax<2.0) group (52.0±14.8 µM), but not in other regions apart from the BAT deposits. The µs' in the supraclavicular region of the BAT (+) group was 8.4±1.7 cm(-1), which was significantly higher than that of BAT (-) group (4.3±1.0 cm(-1)), but not in other regions. The area under the receiver operating characteristic curve closest to (0, 1) for [total-Hb] and µs' to discriminate BAT (+) from BAT (-) was 72.5 µM and 6.3 cm(-1), respectively. The sensitivity, specificity, and accuracy for both parameters were 87.5, 100, and 93.3%, respectively. Our novel NIRTRS method is noninvasive, simple, and inexpensive compared with FDG-PET/CT, and is reliable for detecting human BAT.

Kaempferia parviflora extract increases whole-body energy expenditure in humans: roles of brown adipose tissue.

Kaempferia parviflora 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 significantly, showing a maximal increase of 229±69 kJ/d at 60 min, while it did not change after placebo ingestion. To evaluate BAT activity, the subjects underwent fluorodeoxyglucose-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 (351±50 kJ/d at 60 min), but not in the low activity group. Placebo ingestion did not cause any significant 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.

Recruited brown adipose tissue as an antiobesity agent in humans.

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.

Grains of paradise (Aframomum melegueta) extract activates brown adipose tissue and increases whole-body energy expenditure in men.

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 19°C 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 27°C before and after oral ingestion of GP extract (40 mg) in a single-blind, randomised, placebo-controlled, 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 whole-body EE through the activation of BAT in human subjects.

Nonpungent capsaicin analogs (capsinoids) increase energy expenditure through the activation of brown adipose tissue in humans.

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.

Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans.

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, whole-body energy expenditure, and thermogenesis in healthy adult men.

Brown adipose tissue (BAT) can be identified by (18)F-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.

Polymorphism, heteroplasmy, mitochondrial fusion and diabetes.

Mitochondrial DNA (mtDNA) is highly susceptible to mutations that result in polymorphisms and diseases including diabetes. We analyzed heteroplasmy, polymorphisms related to diabetes, and complementation by fusogenic proteins. Cytoplast fusion and microinjection allow, defects in mutated mtDNA inside a heteroplasmic cell to be complemented by fusing two mitochondria via human fusogenic proteins. We characterized three hfzos as well as two OPAls that prevent apoptosis. Two coiled coil domains and GTPase domains in these fusogenic proteins regulate membrane fusion. The hfzo genes were expressed mainly in the brain and in muscle that are postmitotic, but not in the pancreas. Under the influence of polymorphisms of mtDNA and nDNA, the vicious circle of reactive oxygen species and mutations in cell can be alleviated by mitochondrial fusion.