High Incidence of Metabolically Active Brown Adipose Tissue in Healthy Adult Humans

Saito, Masayuki; Okamatsu‐Ogura, Yuko; Matsushita, M.; Watanabe, Kenta; Yoneshiro, Takeshi; Nio‐Kobayashi, Junko; Iwanaga, Toshihiko; Miyagawa, Masao; Kameya, Toshimitsu; Nakada, Kunihiro; Kawai, Yuko; Tsujisaki, Masayuki

doi:10.2337/db09-0530

Cited by 1,700 publications

(1,684 citation statements)

References 24 publications

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“…The amount of BAT in humans has been shown to vary with age, BMI, and gender, compounding the complexity of these studies. [11][12][13] Beige adipocytes are found interspersed within the WAT, [14][15][16] specifically the subcutaneous WAT (scWAT), in response to various stimuli including cold exposure and b-adrenergic stimulation. Beige cells come from a Myf5-lineage distinguishing them from BAT, but can, upon stimulation, express high levels of UCP1 and contribute to non-shivering thermogenesis.…”

Section: Adipose Tissuementioning

confidence: 99%

“…76 It is possible that the type of exercise, the ambient temperature in which the exercise occurs, the pre-training BMI, and the initial cardiorespiratory fitness levels of the subjects may all be important factors in determining if exercise training in humans induces a beiging of WAT. Another potential explanation is that similar to the variable effects of cold on BAT activity in humans, 11,13 some individuals may have a greater genetic propensity to increase beiging of scWAT in response to exercise training. Additional studies are needed to fully understand if beiging of scWAT is an important physiological response to exercise in human subjects, and in subjects that demonstrate beiging of scWAT, if there are metabolic consequences to this adaptation.…”

Section: Does Exercise Cause Beiging Of Wat In Humans?mentioning

confidence: 99%

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Exercise regulation of adipose tissue

2016

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Exercise training results in adaptations to numerous organ systems and offers protection against metabolic disorders including obesity and type 2 diabetes, and recent reports suggest that adipose tissue may play a role in these beneficial effects of exercise on overall health. Multiple studies have investigated the effects of exercise training on both white adipose tissue (WAT) and brown adipose tissue (BAT), as well as the induction of beige adipocytes. Studies from both rodents and humans show that there are exercise training-induced changes in WAT including decreased cell size and lipid content, and increased mitochondrial activity. In rodents, exercise training causes an increased beiging of WAT. Whether exercise training causes a beiging of human scWAT, as well as which factors contribute to the exercise-induced beiging of WAT are areas of current investigation. Studies investigating the effects of exercise training on BAT mass and function have yielded conflicting data, and hence, is another area of intensive investigation. This review will focus on studies aimed at elucidating the mechanisms regulating exercise training induced-adaptations to adipose tissue.

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Section: Adipose Tissuementioning

confidence: 99%

Section: Does Exercise Cause Beiging Of Wat In Humans?mentioning

confidence: 99%

Exercise regulation of adipose tissue

2016

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“…1 Obesity is defined by the expansion of white adipose tissue (WAT), but recent evidence suggests that the adult human body also contains functionally distinct, brown adipose tissue. [2][3][4][5][6][7][8] In contrast to WAT, which has a primary role in energy storage, brown adipose tissue specializes in energy dissipation as heat (Cannon and Nedergaard 9 ). This thermogenic property of brown fat results from its high content of mitochondria, cell organelles where energy dissipation occurs.…”

Section: Introductionmentioning

confidence: 99%

High-fat diet induces emergence of brown-like adipocytes in white adipose tissue of spontaneously hypertensive rats

et al. 2011

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Obesity has a profound adverse impact on health. In this study, we present evidence for high-fat diet (HFD)-induced emergence of brown-like adipocytes in white adipose tissue (WAT) of the spontaneously hypertensive rat (SHR). We studied adult males fed a HFD or normal diet (ND) for 12 weeks. At the end of the 12-week dietary intervention, HFD compared with ND rats showed significantly higher whole-body energy expenditure. HFD vs. ND rats also showed higher expression of genes involved in fatty acid oxidation, mitochondrial biogenesis and brown fat adipogenesis, as well as augmented mitochondrial mass in WAT but not in the liver or skeletal muscle. Consistent with the molecular changes, in HFD but not in ND rats, histological and immunohistochemistry-based analyses of WAT demonstrated the presence of small multilocular cells staining positively for uncoupling protein 1, indicating the emergence of brown-like adipocytes in WAT. Our results suggest that SHR may have the capacity to increase energy expenditure in response to a chronic HFD that may be linked to the emergence of brown-like adipocytes in WAT. Thus, the SHR may be an important genetic model to uncover novel mechanisms of resistance to dietary obesity.

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“…Three manuscripts published in the same issue of the New England Journal of Medicine, from the USA (Cypess et al 2009), Finland (Virtanen et al 2009), and the Netherlands (van Marken Lichtenbelt et al 2009), and followed shortly by a manuscript from Japan (Saito et al 2009), clearly indicated that BAT was present in a significant number of adults and that its presence and activity (measured by proxy as 18 F FDG uptake by PET scanning) correlated with indices of healthy metabolism. Conversely, obesity, diabetes and age inversely correlated with BAT activity (Pfannenberg et al 2010).…”

Section: Implications Of the Rediscovery Of Bat In Adult Humansmentioning

confidence: 99%

Human Brown Adipose Tissue Plasticity: Hormonal and Environmental Manipulation

Celi

2017

Research and Perspectives in Endocrine Interactions

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Brown adipose tissue (BAT), brown-in-white ("brite") and "beige" adipocytes share the unique ability of converting chemical energy into heat and play a critical role in the adaptive thermogenesis response promoting nonshivering thermogenesis. Uncoupling Protein-1 (UCP1), which allows the uncoupling of substrate oxidation from phosphorylation of ADP, represents the molecular signature of BAT and beige adipocytes. Until recently, the physiologic role of BAT and beige adipocytes depots was thought to be limited to small mammalians and newborns.The discovery of BAT in adult humans and the demonstration of the presence of inducible BAT activity in white adipose tissue by beige adipocytes have generated enthusiasm as potential targets for treatment of obesity and other disorders due to sustained positive energy balance. These findings are particularly important since in vitro studies have demonstrated that preadipocytes can be directed toward a common brown phenotype by multiple pathways that, in turn, may be exploited for therapeutic interventions. In adult humans, BAT activity is more evident in deep neck fat depots and, to a lesser degree, in subcutaneous adipose tissue, with a transcriptome signature resembling the rodent beige fat. This observation supports the hypothesis that human BAT activity and capacity can be modulated. To this end, we have directed our translational research program toward the characterization of beige fat in humans and on the effects of hormonal and environmental drivers in the adaptive thermogenesis response. Mild cold exposure, within the temperature range commonly employed in climate-controlled buildings, is sufficient to generate a significant increase in non-shivering thermogenesis driven by BAT and beige adipocyte activation. In turn, adaptive thermogenesis generates a specific hormonal signature and promotes glucose disposal. Chronic exposure to mild cold induces expansion of BAT mass and activity, whereas exposure to warm climate abrogates them. Additionally, the metabolic effects of BAT mass expansion are evident only upon stimulation of BAT activity, indicating that both F. S. Celi (*) Division of Endocrinology Diabetes and Metabolism, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA e-mail: Francesco.celi@vchuhealth.org 2 expansion and activation of BAT are necessary and complementary strategies to pursue. From an experimental standpoint, human preadipocytes represent a viable experimental platform to mechanistically interrogate different pathways that are able to expand and activate browning. Our laboratory has focused on studying FGF-21, and FNDC5/irisin in their capacity to promote the browning process. Compared to a white differentiation medium, the addition of either FGF-21 or FNDC5 results in a reprogramming toward a brown phenotype, as indicated by the display of brown transcriptome signature and, functionally, by the increase in oxygen consumption following catecholamine treatment, indicating an increase in substrate utilizat...

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High Incidence of Metabolically Active Brown Adipose Tissue in Healthy Adult Humans

Cited by 1,700 publications

References 24 publications

Exercise regulation of adipose tissue

Exercise regulation of adipose tissue

High-fat diet induces emergence of brown-like adipocytes in white adipose tissue of spontaneously hypertensive rats

Human Brown Adipose Tissue Plasticity: Hormonal and Environmental Manipulation

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