Brown Adipose Tissue - role in metabolic disorders

Brown adipose tissue, a thermogenic organ, previously thought to be present in only small mammals and children has recently been identified in adult humans. Located primarily in the supraclavicular and cervical area, it produces heat by uncoupling oxidative phosphorylation due to the unique presence of uncoupling protein 1 by a process called nonshivering thermogenesis. BAT activity depends on many factors including age, sex, adiposity and outdoor temperature. Positron-emission tomography using 18F-fluorodeoxyglucose and computed tomography (18F-FDG PET–CT), magnetic resonance imaging (MRI) and thermal imaging (IRT) are among several methods used to detect BAT in humans. The importance of BAT is due to its role in whole body energy expenditure and fuel metabolism. Thus it is postulated that it may be useful in the treatment of metabolic diseases. However, there are still many unanswered questions to the clinical usefulness of this novel tissue. IMC J Med Sci 2019; 13(1): 002

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Evaluation of Active Brown Adipose Tissue by the Use of Hyperpolarized [1-13C]Pyruvate MRI in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms19092597 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2597 ◽

Cited By ~ 5

Author(s):

Mette Riis-Vestergaard ◽

Peter Breining ◽

Steen Pedersen ◽

Christoffer Laustsen ◽

Hans Stødkilde-Jørgensen ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Cold Exposure ◽

Fdg Pet ◽

Metabolic Diseases ◽

Uncoupling Protein ◽

Protein Levels ◽

Positron Emission ◽

Brown Adipose

The capacity to increase energy expenditure makes brown adipose tissue (BAT) a putative target for treatment of metabolic diseases such as obesity. Presently, investigation of BAT in vivo is mainly performed by fluoro-d-glucose positron emission tomography (FDG PET)/CT. However, non-radioactive methods that add information on, for example, substrate metabolism are warranted. Thus, the aim of this study was to evaluate the potential of hyperpolarized [1-13C]pyruvate Magnetic Resonance Imaging (HP-MRI) to determine BAT activity in mice following chronic cold exposure. Cold (6 °C) and thermo-neutral (30 °C) acclimated mice were scanned with HP-MRI for assessment of the interscapular BAT (iBAT) activity. Comparable mice were scanned with the conventional method FDG PET/MRI. Finally, iBAT was evaluated for gene expression and protein levels of the specific thermogenic marker, uncoupling protein 1 (UCP1). Cold exposure increased the thermogenic capacity 3–4 fold (p < 0.05) as measured by UCP1 gene and protein analysis. Furthermore, cold exposure as compared with thermo-neutrality increased iBAT pyruvate metabolism by 5.5-fold determined by HP-MRI which is in good agreement with the 5-fold increment in FDG uptake (p < 0.05) measured by FDG PET/MRI. iBAT activity is detectable in mice using HP-MRI in which potential changes in intracellular metabolism may add useful information to the conventional FDG PET studies. HP-MRI may also be a promising radiation-free tool for repetitive BAT studies in humans.

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Imaging Metabolically Active Fat: A Literature Review and Mechanistic Insights

International Journal of Molecular Sciences ◽

10.3390/ijms20215509 ◽

2019 ◽

Vol 20 (21) ◽

pp. 5509

Author(s):

Joseph Frankl ◽

Amber Sherwood ◽

Deborah J. Clegg ◽

Philipp E. Scherer ◽

Orhan K. Öz

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Cancer Surveillance ◽

Mitochondrial Uncoupling ◽

Positron Emission ◽

Brown Adipose ◽

Pet Ct ◽

Brown Adipose Tissue Activity ◽

Magnetic Resonance Imaging Mri ◽

Fdg Pet Ct

Currently, obesity is one of the leading causes death in the world. Shortly before 2000, researchers began describing metabolically active adipose tissue on cancer-surveillance 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in adult humans. This tissue generates heat through mitochondrial uncoupling and functions similar to classical brown and beige adipose tissue in mice. Despite extensive research, human brown/beige fat’s role in resistance to obesity in humans has not yet been fully delineated. FDG uptake is the de facto gold standard imaging technique when studying brown adipose tissue, although it has not been rigorously compared to other techniques. We, therefore, present a concise review of established and emerging methods to image brown adipose tissue activity in humans. Reviewed modalities include anatomic imaging with CT and magnetic resonance imaging (MRI); molecular imaging with FDG, fatty acids, and acetate; and emerging techniques. FDG-PET/CT is the most commonly used modality because of its widespread use in cancer imaging, but there are mechanistic reasons to believe other radiotracers may be more sensitive and accurate at detecting brown adipose tissue activity. Radiation-free modalities may help the longitudinal study of brown adipose tissue activity in the future.

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The Role of AMPK Signaling in Brown Adipose Tissue Activation

Cells ◽

10.3390/cells10051122 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1122

Author(s):

Jamie I. van der van der Vaart ◽

Mariëtte R. Boon ◽

Riekelt H. Houtkooper

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Whole Body ◽

Ampk Signaling ◽

Mitochondrial Homeostasis ◽

Brown Adipose ◽

Metabolic Stresses ◽

Amp Activated Protein Kinase ◽

Body Energy

Obesity is becoming a pandemic, and its prevalence is still increasing. Considering that obesity increases the risk of developing cardiometabolic diseases, research efforts are focusing on new ways to combat obesity. Brown adipose tissue (BAT) has emerged as a possible target to achieve this for its functional role in energy expenditure by means of increasing thermogenesis. An important metabolic sensor and regulator of whole-body energy balance is AMP-activated protein kinase (AMPK), and its role in energy metabolism is evident. This review highlights the mechanisms of BAT activation and investigates how AMPK can be used as a target for BAT activation. We review compounds and other factors that are able to activate AMPK and further discuss the therapeutic use of AMPK in BAT activation. Extensive research shows that AMPK can be activated by a number of different kinases, such as LKB1, CaMKK, but also small molecules, hormones, and metabolic stresses. AMPK is able to activate BAT by inducing adipogenesis, maintaining mitochondrial homeostasis and inducing browning in white adipose tissue. We conclude that, despite encouraging results, many uncertainties should be clarified before AMPK can be posed as a target for anti-obesity treatment via BAT activation.

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KCTD10 regulates brown adipose tissue thermogenesis and metabolic function via Notch Signaling

Journal of Endocrinology ◽

10.1530/joe-21-0016 ◽

2021 ◽

Author(s):

Mingsheng Ye ◽

Liping Luo ◽

Qi Guo ◽

Guanghua Lei ◽

Chao Zeng ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Notch Signaling ◽

Molecular Mechanisms ◽

Uncoupling Protein ◽

Notch Signaling Pathway ◽

Whole Body ◽

Brown Adipocyte ◽

Metabolic Function ◽

Brown Adipose

Brown adipose tissue (BAT) is emerging as a target to beat obesity through the dissipation of chemical energy to heat. However, the molecular mechanisms of brown adipocyte thermogenesis remain to be further elucidated. Here, we show that KCTD10, a member of the polymerase delta-interacting protein 1 (PDIP1) family, was reduced in BAT by cold stress and a β3 adrenoceptor agonist. Moreover, KCTD10 level increased in the BAT of obese mice, and KCTD10 overexpression attenuates uncoupling protein 1 (UCP1) expression in primary brown adipocytes. BAT-specific KCTD10 knockdown mice had increased thermogenesis and cold tolerance protecting from high fat diet (HFD)-induced obesity. Conversely, overexpression of KCTD10 in BAT caused reduced thermogenesis, cold intolerance, and obesity. Mechanistically, inhibiting Notch signaling restored the KCTD10 overexpression suppressed thermogenesis. Our study presents that KCTD10 serves as an upstream regulator of notch signaling pathway to regulate BAT thermogenesis and whole-body metabolic function.

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Assessment of the Aging of the Brown Adipose Tissue by 18F-FDG PET/CT Imaging in the Progeria Mouse Model Lmna−/−

Contrast Media & Molecular Imaging ◽

10.1155/2018/8327089 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Zhengjie Wang ◽

Xiaolong Xu ◽

Yi Liu ◽

Yongheng Gao ◽

Fei Kang ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Fdg Pet ◽

Uncoupling Protein ◽

Ct Imaging ◽

Terminal Deoxynucleotidyl Transferase ◽

Expression Levels ◽

Brown Adipose ◽

Pet Ct ◽

Fdg Pet Ct

Brown adipose tissue (BAT) is an important energy metabolic organ that is highly implicated in obesity, type 2 diabetes, and atherosclerosis. Aging is one of the most important determinants of BAT activity. In this study, we used 18F-FDG PET/CT imaging to assess BAT aging in Lmna−/− mice. The maximum standardized uptake value (SUVMax) of the BAT was measured, and the target/nontarget (T/NT) values of BAT were calculated. The transcription and the protein expression levels of the uncoupling protein 1 (UCP1), beta3-adrenergic receptor (β3-AR), and the PR domain-containing 16 (PRDM16) were measured by quantitative real-time polymerase chain reaction (RT-PCR) and Western blotting or immunohistochemical analysis. Apoptosis and cell senescence rates in the BAT of WT and Lmna−/− mice were determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and by CDKN2A/p16INK4a immunohistochemical staining, respectively. At 14 weeks of age, the BAT SUVMax and the expression levels of UCP1, β3-AR, and PRDM16 in Lmna−/− mice were significantly reduced relative to WT mice. At the same time, the number of p16INK4a and TUNEL positively stained cells (%) increased in Lmna−/− mice. Collectively, our results indicate that the aging characteristics and the aging regulatory mechanism in the BAT of Lmna−/− mice can mimic the normal BAT aging process.

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Front cover: Cyanidin-3-glucoside increases whole body energy metabolism by upregulating brown adipose tissue mitochondrial function

Molecular Nutrition & Food Research ◽

10.1002/mnfr.201770111 ◽

2017 ◽

Vol 61 (11) ◽

pp. 1770111

Author(s):

Yilin You ◽

Xiaoxue Yuan ◽

Xiaomeng Liu ◽

Chen Liang ◽

Minghui Meng ◽

...

Keyword(s):

Adipose Tissue ◽

Energy Metabolism ◽

Brown Adipose Tissue ◽

Mitochondrial Function ◽

Whole Body ◽

Front Cover ◽

Brown Adipose ◽

Body Energy

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Whole Body and Regional Quantification of Active Human Brown Adipose Tissue Using 18F-FDG PET/CT

Journal of Visualized Experiments ◽

10.3791/58469 ◽

2019 ◽

Cited By ~ 1

Author(s):

Katherine Kim ◽

Shan Huang ◽

Laura A. Fletcher ◽

Alana E. O'Mara ◽

Ilan Tal ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Fdg Pet ◽

Whole Body ◽

Brown Adipose ◽

Pet Ct ◽

Fdg Pet Ct

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Leucine Potentiates Glucose-mediated 18F-FDG Uptake in Brown Adipose Tissue via β-Adrenergic Activation

Biomedicines ◽

10.3390/biomedicines8060159 ◽

2020 ◽

Vol 8 (6) ◽

pp. 159

Author(s):

Brenda Huska ◽

Sarah Niccoli ◽

Christopher P. Phenix ◽

Simon J. Lees

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Whole Body ◽

Fdg Uptake ◽

Standardized Uptake Values ◽

Positron Emission ◽

Brown Adipose ◽

18F Fdg ◽

Adrenergic Activation

Significant depots of brown adipose tissue (BAT) have been identified in many adult humans through positron emission tomography (PET), with the amount of BAT being inversely correlated with obesity. As dietary activation of BAT has implications for whole body glucose metabolism, leucine was used in the present study to determine its ability to promote BAT activation resulting in increased glucose uptake. In order to assess this, 2-deoxy-2-(fluorine-18)fluoro-d-glucose (18F-FDG) uptake was measured in C57BL/6 mice using microPET after treatment with leucine, glucose, or both in interscapular BAT (IBAT). Pretreatment with propranolol (PRP) was used to determine the role of β-adrenergic activation in glucose and leucine-mediated 18F-FDG uptake. Analysis of maximum standardized uptake values (SUVMAX) determined that glucose administration increased 18F-FDG uptake in IBAT by 25.3%. While leucine did not promote 18F-FDG uptake alone, it did potentiate glucose-mediated 18F-FDG uptake, increasing 18F-FDG uptake in IBAT by 22.5%, compared to glucose alone. Pretreatment with PRP prevented the increase in IBAT 18F-FDG uptake following the combination of glucose and leucine administration. These data suggest that leucine is effective in promoting BAT 18F-FDG uptake through β-adrenergic activation in combination with glucose.

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