Article

Transcriptional control of brown adipocyte development and physiological function--of mice and men.

Dana-Farber Cancer Institute, Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Genes & development (Impact Factor: 12.64). 05/2009; 23(7):788-97. DOI: 10.1101/gad.1779209
Source: PubMed

ABSTRACT The last several years have seen an explosion of information relating to the transcriptional control of brown fat cell development. At the same time, new data have emerged that clearly demonstrate that adult humans do indeed have substantial amounts of functioning brown adipose tissue (BAT). Together, these advances are stimulating a reassessment of the role of brown adipose tissue in human physiology and pathophysiology. These data have also opened up exciting new opportunities for the development of entirely novel classes of therapeutics for metabolic diseases like obesity and type 2 diabetes.

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    ABSTRACT: Objective Augmented brown adipose tissue (BAT) mass and activity leads to higher basic metabolic rate which is beneficial against obesity. Our aim was to investigate whether habitual (i.e., usual weekly participation) physical activity is linked with BAT activity and mass in humans, in a group of patients undergoing 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scanning.DesignCross-sectional study.PatientsForty cancer patients [26 male; 14 female; age 52.7±17.5; body mass index (BMI) 26.4±4.5].MeasurementsPatients completed the “usual week” form of the International Physical Activity Questionnaire and underwent assessment of BAT activity/mass via 18F-fluorodeoxyglucose PET/CT.ResultsWe detected a significant association between habitual physical activity (METs-minute/week) and BAT activity [normalized by BW (τ=0.28, p=0.02), BSA (τ=0.29, p=0.02), and LBM (τ=0.38, p=0.002)]. We also found a significant negative relationship between BMI and BAT activity [normalized by BW (τ=-0.30, p=0.006), BSA (τ=-0.31, p=0.004), and LBM (τ=-0.45, p=0.001)] as well as a significant negative relationship between age and BAT activity [normalized by LBM (τ=-0.28, p=0.01)]. The results also indicate significant differences between low/moderate/high levels of habitual physical activity and BAT activity (P<0.05). Moreover, BAT activity was different across the BMI categories (normal/overweight/obese) in both sexes (P<0.05). Finally, BAT activity was greater in women than in men (P<0.05).Conclusions Increased participation in habitual physical activity is associated with higher BAT activity. Moreover, individuals with normal BMI demonstrate higher BAT activity compared to overweight and obese individuals. Finally, age is inversely linked with BAT activity, while women demonstrate higher BAT activity than men.This article is protected by copyright. All rights reserved.
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    ABSTRACT: In humans, two functionally different types of adipose tissue coexist, white adipose tissue (WAT) and brown adipose tissue (BAT). WAT is involved in energy storage while BAT is involved in energy expenditure. Increased amounts of WAT may contribute to the development of metabolic disorders, such as obesity-associated type 2 diabetes mellitus (T2DM) and cardiovascular diseases. In contrast, the thermogenic function of BAT allows high consumption of fatty acids due to the activity of uncoupling protein 1 (UCP1) in the internal mitochondrial membrane. Interestingly, obesity reduction and insulin sensitization have been achieved by BAT activation/regeneration in animal models.This review describes the origin, function and differentiation mechanisms of BAT in order to identify new therapeutic strategies for the treatment of metabolic disorders related to obesity. Based on animal studies, novel approaches for BAT regeneration combining stem cells from the adipose tissue with active components, such as melatonin, may have potential for the treatment of metabolic disorders in humans.
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