The Remaining Mysteries about Brown Adipose Tissues

Brown adipose tissue (BAT), which is a thermogenic fat tissue originally discovered in small hibernating mammals, is believed to exert anti-obesity effects in humans. Although evidence has been accumulating to show the importance of BAT in metabolism regulation, there are a number of unanswered questions. In this review, we show the remaining mysteries about BATs. The distribution of BAT can be visualized by nuclear medicine examinations; however, the precise localization of human BAT is not yet completely understood. For example, studies of 18F-fluorodeoxyglucose PET/CT scans have shown that interscapular BAT (iBAT), the largest BAT in mice, exists only in the neonatal period or in early infancy in humans. However, an old anatomical study illustrated the presence of iBAT in adult humans, suggesting that there is a discrepancy between anatomical findings and imaging data. It is also known that BAT secretes various metabolism-improving factors, which are collectively called as BATokines. With small exceptions, however, their main producers are not BAT per se, raising the possibility that there are still more BATokines to be discovered. Although BAT is conceived as a favorable tissue from the standpoint of obesity prevention, it is also involved in the development of unhealthy conditions such as cancer cachexia. In addition, a correlation between browning of mammary gland and progression of breast cancers was shown in a xenotransplantation model. Therefore, the optimal condition should be carefully determined when BAT is considered as a measure the prevention of obesity and improvement of metabolism. Solving BAT mysteries will open a new door for health promotion via advanced understanding of metabolism regulation system.

Download Full-text

Brown adipose tissue: what have we learned since its recent identification in human adults

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/0004-2730000003492 ◽

2014 ◽

Vol 58 (9) ◽

pp. 889-899 ◽

Cited By ~ 13

Author(s):

Bruno Halpern ◽

Marcio Correa Mancini ◽

Alfredo Halpern

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Mitochondrial Uncoupling ◽

Positron Emission ◽

Brown Adipose ◽

Adult Humans ◽

Human Adults ◽

Real Importance ◽

Diet Induced Thermogenesis ◽

Fluorodeoxyglucose Pet

Brown adipose tissue, an essential organ for thermoregulation in small and hibernating mammals due to its mitochondrial uncoupling capacity, was until recently considered to be present in humans only in newborns. The identification of brown adipose tissue in adult humans since the development and use of positron emission tomography marked with 18-fluorodeoxyglucose (PET-FDG) has raised a series of doubts and questions about its real importance in our metabolism. In this review, we will discuss what we have learnt since its identification in humans as well as both new and old concepts, some of which have been marginalized for decades, such as diet-induced thermogenesis. Arq Bras Endocrinol Metab. 2014;58(9):889-99

Download Full-text

Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00482.2015 ◽

2016 ◽

Vol 311 (1) ◽

pp. E95-E104 ◽

Cited By ~ 43

Author(s):

Aliya Gifford ◽

Theodore F. Towse ◽

Ronald C. Walker ◽

Malcolm J. Avison ◽

E. Brian Welch

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Fdg Pet ◽

Whole Body ◽

Subcutaneous White Adipose Tissue ◽

Brown Adipose ◽

Pet Ct ◽

Adult Humans ◽

Mri Scans ◽

Whole Body Metabolism

Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [18F]fluorodeoxyglucose ([18F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [18F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means ± SD; 60.2 ± 7.6 vs. 62.4 ± 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; −69.4 ± 11.5 vs. −74.5 ± 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.

Download Full-text

A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00298.2010 ◽

2010 ◽

Vol 299 (4) ◽

pp. E601-E606 ◽

Cited By ~ 195

Author(s):

Paul Lee ◽

Jerry R. Greenfield ◽

Ken K. Y. Ho ◽

Michael J. Fulham

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Energy Homeostasis ◽

Fasting Glucose ◽

Apparent Prevalence ◽

Positron Emission ◽

Brown Adipose ◽

Pet Ct ◽

Adult Humans ◽

Average Probability

Brown adipose tissue (BAT) plays a major role in energy homeostasis in animals. Detection of BAT using positron emission tomography (PET)-CT in humans has challenged the view that BAT disappears after infancy. Several recent studies, based on analysis of single scans, have reported a low prevalence of only 5–10% in humans, casting doubt on its significance. We undertook a critical analysis of the sensitivity, reproducibility, and accuracy of PET-CT to deduce the prevalence of BAT and factors associated with its detection in adult humans. In a retrospective evaluation of PET-CT, using [18F]fluorodeoxyglucose, performed in 2,934 patients, BAT was identified in 250 patients, yielding an apparent prevalence of 8.5%. Among those patients with BAT, 145 were scanned more than once. The frequency of another scan being positive increased from 8 to 65% for one to more than four additional studies. The average probability of obtaining another positive scan among patients with BAT is 13%, from which the prevalence of BAT is estimated at 64%. BAT was more commonly detected in women, in younger (36 ± 1 vs. 52 ± 1 years, P < 0.001) and leaner (20.1 ± 0.9 vs. 24.9 ± 0.9 kg/m2, P < 0.01) individuals. Fasting glucose was lower in those with BAT than those without (4.9 ± 0.1 vs. 5.5 ± 0.1 mmol/l, P < 0.01). Among patients scanned more than once, BAT was detected when body weight and fasting glucose were lower (54.9 ± 0.5 vs. 58.2 ± 0.8 kg, P < 0.001 and 4.9 ± 0.3 vs. 5.5 ± 0.3 mmol/l, P = 0.03). We conclude that BAT is present in the majority of adult humans. Presence of BAT correlates negatively with body mass index and glucose concentration. BAT may play an important role in energy homeostasis in adults.

Download Full-text

Faculty Opinions recommendation of Identification and importance of brown adipose tissue in adult humans.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1158818.626120 ◽

2009 ◽

Author(s):

Harold Bays

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Brown Adipose ◽

Adult Humans

Download Full-text

Faculty Opinions recommendation of Identification and importance of brown adipose tissue in adult humans.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1158818.622481 ◽

2009 ◽

Author(s):

Chantal Chenu

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Brown Adipose ◽

Adult Humans

Download Full-text

[18F]-florbetaben PET/CT Imaging in the Alzheimer’s Disease Mouse Model APPswe/PS1dE9

Current Alzheimer Research ◽

10.2174/1567205015666181022095904 ◽

2018 ◽

Vol 16 (1) ◽

pp. 49-55 ◽

Cited By ~ 1

Author(s):

J. Stenzel ◽

C. Rühlmann ◽

T. Lindner ◽

S. Polei ◽

S. Teipel ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

New Drugs ◽

Imaging Data ◽

Wild Type ◽

Preclinical Research ◽

Standardized Uptake Values ◽

Pet Ct

Background: Positron-emission-tomography (PET) using 18F labeled florbetaben allows noninvasive in vivo-assessment of amyloid-beta (Aβ), a pathological hallmark of Alzheimer’s disease (AD). In preclinical research, [18F]-florbetaben-PET has already been used to test the amyloid-lowering potential of new drugs, both in humans and in transgenic models of cerebral amyloidosis. The aim of this study was to characterize the spatial pattern of cerebral uptake of [18F]-florbetaben in the APPswe/ PS1dE9 mouse model of AD in comparison to histologically determined number and size of cerebral Aβ plaques. Methods: Both, APPswe/PS1dE9 and wild type mice at an age of 12 months were investigated by smallanimal PET/CT after intravenous injection of [18F]-florbetaben. High-resolution magnetic resonance imaging data were used for quantification of the PET data by volume of interest analysis. The standardized uptake values (SUVs) of [18F]-florbetaben in vivo as well as post mortem cerebral Aβ plaque load in cortex, hippocampus and cerebellum were analyzed. Results: Visual inspection and SUVs revealed an increased cerebral uptake of [18F]-florbetaben in APPswe/ PS1dE9 mice compared with wild type mice especially in the cortex, the hippocampus and the cerebellum. However, SUV ratios (SUVRs) relative to cerebellum revealed only significant differences in the hippocampus between the APPswe/PS1dE9 and wild type mice but not in cortex; this differential effect may reflect the lower plaque area in the cortex than in the hippocampus as found in the histological analysis. Conclusion: The findings suggest that histopathological characteristics of Aβ plaque size and spatial distribution can be depicted in vivo using [18F]-florbetaben in the APPswe/PS1dE9 mouse model.

Download Full-text

THU0319 DEVELOPMENT AND OUTCOME OF AORTIC COMPLICATIONS DURING TOCILIZUMAB TREATMENT OF GCA AND HISTOPATHOLOGIC EVIDENCE OF RESIDUAL INFLAMMATION-A CASE SERIES.

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4660 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 388.2-389

Author(s):

A. Rubbert-Roth ◽

P. K. Bode ◽

T. Langenegger ◽

C. Pfofe ◽

T. Neumann ◽

...

Keyword(s):

Structural Changes ◽

Case Series ◽

Aortic Aneurysms ◽

Imaging Data ◽

Limited Data ◽

Retrospective Case ◽

Pet Ct ◽

Fdg Pet Ct ◽

Pet Ct Scan

Background:Giant cell arteritis (GCA) may affect the aorta and the large aortic branches and lead to dissections and aortic aneurysms. Tocilizumab (TCZ) treatment has the capacity to control aortic inflammation as has been demonstrated by CRP normalization and imaging data. However, limited data are available on the histopathological findings obtained from patients who underwent surgery because of aortic complications during TCZ treatment.Objectives:We report on 5 patients with aortitis who were treated with TCZ and developed aortic complications.Methods:We describe a retrospective case series of patients with GCA treated with TCZ, who presented in our clinic between 2011 and 2019. Three patients underwent surgery. Histopathologic examination was performed in specimen from all of them.Results:Five female patients were diagnosed with GCA (4/5) or Takaysu arteritis (1/5) involving the aorta, all them diagnosed by MR angiography and/or FDG PET CT scan. Three patients (one with aortic aneurysm, one with dissection) underwent surgery after having been treated with TCZ for seven weeks, nine months and four years, respectively. Imaging before surgery showed remission on MRI and/or PET-CT in all cases. At the time of surgery, all patients showed normalized CRP and ESR values. Histopathological evaluation of the aortic wall revealed infiltrates, consisting predominantly of CD3+CD4+ T cells. Enlargement of pre-existing aneuryms was observed in the other two patients 10 weeks and 4 months after discontinuation of TCZ, respectively. Both patients were not eligible for surgical intervention and died during follow-up.Conclusion:Our case series suggests that during treatment with TCZ, regular imaging is necessary in this patient population to detect development of structural changes such as aneurysms or dissections. Despite treatment, residual inflammation might persist which could contribute to eventual aortic complications.Disclosure of Interests:Andrea Rubbert-Roth Consultant of: Abbvie, BMS, Chugai, Pfizer, Roche, Janssen, Lilly, Sanofi, Amgen, Novartis, Peter Karl Bode: None declared, Thomas Langenegger: None declared, Claudia Pfofe: None declared, Thomas Neumann: None declared, Olaf Chan-Hi Kim: None declared, Johannes von Kempis Consultant of: Roche

Download Full-text

18 F-FDG PET/CT findings in a patient with paraganglioma: Brown adipose tissue activation due to adrenergic stimulation

Revista Española de Medicina Nuclear e Imagen Molecular (English Edition) ◽

10.1016/j.remnie.2017.10.022 ◽

2018 ◽

Vol 37 (4) ◽

pp. 255-256

Author(s):

Elif Özdemir ◽

Zuhal Kandemir ◽

Mutlay Keskin ◽

Nilufer Yildirim ◽

Didem Özdemir ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Fdg Pet ◽

Adrenergic Stimulation ◽

Ct Findings ◽

Brown Adipose ◽

Pet Ct ◽

Fdg Pet Ct

Download Full-text

3D carotid reconstructions: imaging, pathology, algorithms and pipelines

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2015.170 ◽

2015 ◽

Vol 42 (S1) ◽

pp. S37-S37

Author(s):

AR Khan ◽

M Cocker ◽

JD Spence ◽

M Alturkustani ◽

C Currie ◽

...

Keyword(s):

Ex Vivo ◽

Imaging Data ◽

Spatial Reference ◽

Standard Data ◽

Tissue Sections ◽

Saturation Intensity ◽

Plaque Pathology ◽

Pet Ct ◽

Atherosclerosis Imaging ◽

Ct And Mri

Background: Whole-slide scanning of tissue sections spatially informed by imaging studies offers the opportunity to reconstruct specimens for co-registration to 3D imaging data. Digital image analysis algorithms can be designed to analyze and reconstruct such specimens via electronic “pipelines”. Methods: A goal of the Canadian Atherosclerosis Imaging Network (CAIN) is to improve the assessment of carotid atheromatous disease through studies that inform clinical imaging with gold-standard data (plaque pathology). To achieve this, sectioned atheromas are manually annotated and analyzed by electronic algorithm for pathological features of interest. Resulting images are then reassembled in 3D for registration to ultrasound, CT, PET-CT and MRI studies. Results: Carotid endarterectomy specimens were sub-serially sectioned, stained, digitized and annotated manually and by electronic algorithms. Resulting 2D images were successfully rendered, reassembled and analyzed in 3D using ex-vivo micro-CT as a spatial reference. Furthermore, histology quantification using colour deconvolution was found to be preferred over hue-saturation-intensity methods 94.7-100% of the time in a blinded multiple rater study. Conclusion: Automated “pipelines” greatly facilitate 3D reconstruction in comparison to traditional slice-by-slice methods. Transformations spatially guided by pre-existing imaging data is not only faster, but has superior objectivity and fidelity. With embedded annotations, 3D pathology maps become a rich, micron-level, permanent digital pathological database for correlative studies.

Download Full-text