Identification and Importance of Brown Adipose Tissue in Adult Humans

Research Division, Joslin Diabetes Center, Boston, MA 02215, USA.
New England Journal of Medicine (Impact Factor: 55.87). 05/2009; 360(15):1509-17. DOI: 10.1056/NEJMoa0810780
Source: PubMed

ABSTRACT Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans.
We analyzed 3640 consecutive (18)F-fluorodeoxyglucose ((18)F-FDG) positron-emission tomographic and computed tomographic (PET-CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of (18)F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from the neck and supraclavicular regions in patients undergoing surgery.
Substantial depots of brown adipose tissue were identified by PET-CT in a region extending from the anterior neck to the thorax. Tissue from this region had UCP1-immunopositive, multilocular adipocytes indicating brown adipose tissue. Positive scans were seen in 76 of 1013 women (7.5%) and 30 of 959 men (3.1%), corresponding to a female:male ratio greater than 2:1 (P<0.001). Women also had a greater mass of brown adipose tissue and higher (18)F-FDG uptake activity. The probability of the detection of brown adipose tissue was inversely correlated with years of age (P<0.001), outdoor temperature at the time of the scan (P=0.02), beta-blocker use (P<0.001), and among older patients, body-mass index (P=0.007).
Defined regions of functionally active brown adipose tissue are present in adult humans, are more frequent in women than in men, and may be quantified noninvasively with the use of (18)F-FDG PET-CT. Most important, the amount of brown adipose tissue is inversely correlated with body-mass index, especially in older people, suggesting a potential role of brown adipose tissue in adult human metabolism.

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Available from: Allison Goldfine, May 24, 2014
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    • "In the context of the global obesity epidemic, impacting energy balance in humans without altering either energy consumption or physical activity would be of significant clinical importance. The recent discovery of functional brown adipose tissue (BAT) in adult humans (Cypess et al., 2009; Nedergaard et al., 2007; Saito et al., 2009; van Marken Lichtenbelt et al., 2009; Virtanen et al., 2009) has renewed scientific interest in adipose tissue and its role in energy expenditure. While there is still debate as to whether this tissue is genuine brown adipose tissue (Shinoda et al., 2015; Sidossis and Kajimura, 2015; Wu et al., 2012, 2013), it is indisputable that it contains numerous mitochondria expressing uncoupling protein 1 (UCP1). "
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    ABSTRACT: Since the presence of brown adipose tissue (BAT) was confirmed in adult humans, BAT has become a therapeutic target for obesity and insulin resistance. We examined whether human subcutaneous white adipose tissue (sWAT) can adopt a BAT-like phenotype using a clinical model of prolonged and severe adrenergic stress. sWAT samples were collected from severely burned and healthy individuals. A subset of burn victims were prospectively followed during their acute hospitalization. Browning of sWAT was determined by the presence of multilocular adipocytes, uncoupling protein 1 (UCP1), and increased mitochondrial density and respiratory capacity. Multilocular UCP1-positive adipocytes were found in sWAT samples from burn patients. UCP1 mRNA, mitochondrial density, and leak respiratory capacity in sWAT increased after burn trauma. Our data demonstrate that human sWAT can transform from an energy-storing to an energy-dissipating tissue, which opens new research avenues in our quest to prevent and treat obesity and its metabolic complications. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cell metabolism 08/2015; 22(2):219-27. DOI:10.1016/j.cmet.2015.06.022 · 17.57 Impact Factor
    • "Effect of CDCA Supplementation on BAT Activity Recently, functional brown adipose tissue was discovered in adult humans (Cypess et al., 2009; van Marken Lichtenbelt et al., 2009; Virtanen et al., 2009). However, the role of BAT activation in the battle against the negative metabolic health effects of obesity still needs to be established. "
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    ABSTRACT: The interest in brown adipose tissue (BAT) as a target to combat metabolic disease has recently been renewed with the discovery of functional BAT in humans. In rodents, BAT can be activated by bile acids, which activate type 2 iodothyronine deiodinase (D2) in BAT via the G-coupled protein receptor TGR5, resulting in increased oxygen consumption and energy expenditure. Here we examined the effects of oral supplementation of the bile acid chenodeoxycholic acid (CDCA) on human BAT activity. Treatment of 12 healthy female subjects with CDCA for 2 days resulted in increased BAT activity. Whole-body energy expenditure was also increased upon CDCA treatment. In vitro treatment of primary human brown adipocytes derived with CDCA or specific TGR5 agonists increased mitochondrial uncoupling and D2 expression, an effect that was absent in human primary white adipocytes. These findings identify bile acids as a target to activate BAT in humans. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cell metabolism 07/2015; 22(3). DOI:10.1016/j.cmet.2015.07.002 · 17.57 Impact Factor
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    • "The aging process causes an increase in percent body fat, but the underlying mechanism remains unclear. Current data from rodent experiments have shown that aging is associated with defective differentiation of BAT, alongside morphologic abnormalities and thermogenic dysfunction in rodents (Sellayah and Sikder, 2014) and in humans (Cypess et al., 2009; Stefan et al., 2009; Saito et al., 2009). In fact, interscapular brown fat in aged mice is progressively populated by adipocytes bearing white morphologic characteristics (Sellayah and Sikder, 2014). "
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    ABSTRACT: Initially implicated in the regulation of feeding, orexins/hypocretins are now acknowledged to play a major role in the control of a wide variety of biological processes, such as sleep, energy expenditure, pain, cardiovascular function and neuroendocrine regulation, a feature that make them one of the most pleiotropic families of hypothalamic neuropeptides. While the orexigenic effect of orexins is well described, their central effects on energy expenditure and particularly on brown adipose tissue (BAT) thermogenesis are not totally unraveled. Better understanding of these actions and their possible interrelationship with other hypothalamic systems controlling thermogenesis, such as AMP-activated protein kinase (AMPK) and endoplasmic reticulum (ER) stress, will help to clarify the exact role and pathophysiological relevance of these neuropeptides have on energy balance. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Molecular and Cellular Endocrinology 07/2015; DOI:10.1016/j.mce.2015.07.022 · 4.41 Impact Factor
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