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Sapporo, Japan

Saeki K.,National Health Research Institute | Nishio M.,National Health Research Institute | Yoneshiro T.,Hokkaido University | Nakahara M.,National Health Research Institute | And 10 more authors.
Cell Metabolism | Year: 2012

Brown adipose tissue is attracting much attention due to its antiobestic effects; however, its development and involvement in metabolic improvement remain elusive. Here we established a method for a high-efficiency (>90%) differentiation of human pluripotent stem cells (hPSCs) into functional classical brown adipocytes (BAs) using specific hemopoietin cocktail (HC) without exogenous gene transfer. BAs were not generated without HC, and lack of a component of HC induced white adipocyte (WA) marker expressions. hPSC-derived BA (hPSCdBA) showed respiratory and thermogenic activation by β-adrenergic receptor (AdrRβ) stimuli and augmented lipid and glucose tolerance, whereas human multipotent stromal cell-derived WA (hMSCdWA) improved lipid but inhibited glucose metabolism. Cotransplantation of hPSCdBA normalized hMSCdWA-induced glucose intolerance. Surprisingly, hPSCdBAs expressed various hemopoietin genes, serving as stroma for myeloid progenitors. Moreover, AdrRβ stimuli enhanced recovery from chemotherapy-induced myelosuppression. Our study enhances our understanding of BA, identifying roles in metabolic and hemogenic regulation. © 2012 Elsevier Inc. Source


Yoneshiro T.,Hokkaido University | Aita S.,Tenshi College | Kawai Y.,LSI Sapporo Clinic | Iwanaga T.,Hokkaido University | Saito M.,Tenshi College
American Journal of Clinical Nutrition | Year: 2012

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. © 2012 American Society for Nutrition. Source


Matsushita M.,Tenshi College | Yoneshiro T.,Hokkaido University | Aita S.,Hakodate Junior College | Kameya T.,LSI Sapporo Clinic | And 2 more authors.
International Journal of Obesity | Year: 2014

Background: Brown adipose tissue (BAT) is involved in the regulation of whole-body energy expenditure and adiposity. Some clinical studies have reported an association between BAT and blood glucose in humans. Objective: To examine the impact of BAT on glucose metabolism, independent of that of body fatness, age and sex in healthy adult humans. Methods: Two hundred and sixty healthy volunteers (184 males and 76 females, 20-72 years old) underwent fluorodeoxyglucose-positron emission tomography and computed tomography after 2 h of cold exposure to assess maximal BAT activity. Blood parameters including glucose, HbA1c and low-density lipoprotein (LDL)/high-density lipoprotein-cholesterol were measured by conventional methods, and body fatness was estimated from body mass index (BMI), body fat mass and abdominal fat area. The impact of BAT on body fatness and blood parameters was determined by logistic regression with the use of univariate and multivariate models. Results: Cold-activated BAT was detected in 125 (48%) out of 260 subjects. When compared with subjects without detectable BAT, those with detectable BAT were younger and showed lower adiposity-related parameters such as the BMI, body fat mass and abdominal fat area. Although blood parameters were within the normal range in the two subject groups, HbA1c, total cholesterol and LDL-cholesterol were significantly lower in the BAT-positive group. Blood glucose also tended to be lower in the BAT-positive group. Logistic regression demonstrated that BAT, in addition to age and sex, was independently associated with BMI, body fat mass, and abdominal visceral and subcutaneous fat areas. For blood parameters, multivariate analysis after adjustment for age, sex and body fatness revealed that BAT was a significantly independent determinant of glucose and HbA1c. Conclusion: BAT, independent of age, sex and body fatness, has a significant impact on glucose metabolism in adult healthy humans. © 2014 Macmillan Publishers Limited All rights reserved. Source


Matsushita M.,Tenshi College | Yoneshiro T.,Hokkaido University | Aita S.,Hakodate Junior College | Kamiya T.,Toyo Shinyaku Co. | And 6 more authors.
Journal of Nutritional Science and Vitaminology | Year: 2015

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. © 2015, Center for Academic Publications Japan. All rights reserved. Source


Yoneshiro T.,Hokkaido University | Ogawa T.,Wakunaga Pharmaceutical Co. | Okamoto N.,Wakunaga Pharmaceutical Co. | Matsushita M.,Tenshi College | And 6 more authors.
International Journal of Obesity | Year: 2013

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 β3-adrenergic receptor (β3AR), 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 -3826 A/G polymorphism of the UCP1 gene and 64 Trp/Arg mutation of the β3AR gene. Results: BAT was detected in 88 subjects out of 199 (44%), more in younger (≤30 y.o., 55%) than older subjects (>40 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 β3AR 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%, P<0.05). Visceral fat area of the 2-4 allele group was higher than that of the 0-1 allele group (P<0.05) in older subjects, but not in younger subjects. Conclusion: UCP1 -3826 A/G and β3AR 64 Trp/Arg substitutions accelerate age-related decrease in BAT activity, and thereby may associate with visceral fat accumulation with age. © 2013 Macmillan Publishers Limited. Source

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