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


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.

Download full-text


Available from: Allison Goldfine, May 24, 2014
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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 11/2015; 418:17-26. DOI:10.1016/j.mce.2015.07.022 · 4.41 Impact Factor
  • Source
    • "BAT is found in relative abundance in small mammals, where it plays a key role in thermoregulatory thermogenesis (Cannon and Nedergaard, 2004). Recent studies have confirmed not only its presence but also its functionality in adult humans (Cypess et al., 2009; Virtanen et al., 2009; van Marken Lichtenbelt et al., 2009; Ouellet et al., 2012), which has driven a renewed interest for the role of BAT in energy balance regulation in relation with obesity. There currently is a therapeutic interest in targeting BAT thermogenesis to treat excess fat deposition and related metabolic disorders (Chechi et al., 2014). "
    [Show abstract] [Hide abstract]
    ABSTRACT: It has long been known, in large part from animal studies, that the control of brown adipose tissue (BAT) thermogenesis is insured by the central nervous system, which integrates several stimuli in order to control BAT activation through the sympathetic nervous system (SNS). SNS-mediated BAT activity is governed by diverse neurons found in brain structures involved in homeostatic regulations and whose activity is modulated by various factors including oscillations of energy fluxes. The characterization of these neurons has always represented a challenging issue. The available literature suggests that the neuronal circuits controlling BAT thermogenesis are largely part of an autonomic circuitry involving the hypothalamus, brainstem and the SNS efferent neurons. In the present review, we recapitulate the latest progresses in regards to the hypothalamic regulation of BAT metabolism. We briefly addressed the role of the thermoregulatory pathway and its interactions with the energy balance systems in the control of thermogenesis. We also reviewed the involvement of the brain melanocortin and endocannabinoid systems as well as the emerging role of steroidogenic factor 1 neurons in BAT thermogenesis. Finally, we examined the link existing between these systems and the homeostatic factors that modulate their activities.
    Frontiers in Systems Neuroscience 10/2015; 9. DOI:10.3389/fnsys.2015.00150
  • Source
    • "This infant interscapular BAT expresses genes that are characteristic of classical brown adipocytes (Lidell et al., 2013b). In adult humans, BAT depots are generally heterogeneous, containing multiple cell types, including UCP1-positive and -negative adipocytes (Cypess et al., 2009, 2013; Virtanen et al., 2009). At the molecular level, supraclavicular BAT possesses a molecular signature that closely resembles mouse beige adipocytes (Lee et al., 2014c; Sharp et al., 2012; Shinoda et al., 2015; Wu et al., 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Since brown adipose tissue (BAT) dissipates energy through UCP1, BAT has garnered attention as a therapeutic intervention for obesity and metabolic diseases including type 2 diabetes. As we better understand the physiological roles of classical brown and beige adipocytes, it is becoming clear that BAT is not simply a heat-generating organ. Increased beige fat mass in response to a variety of external/internal cues is associated with significant improvements in glucose and lipid homeostasis that may not be entirely mediated by UCP1. We aim to discuss recent insights regarding the developmental lineages, molecular regulation, and new functions for brown and beige adipocytes.
    Cell metabolism 10/2015; 22(4):546-559. DOI:10.1016/j.cmet.2015.09.007 · 17.57 Impact Factor
Show more

Similar Publications