scholarly journals Spectral Unmixing Imaging for Differentiating Brown Adipose Tissue Mass and Its Activation

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Jing Yang ◽  
Jian Yang ◽  
Chongzhao Ran
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Large Scale ◽  
Near Infrared ◽  
Clinical Analysis ◽  
Spectral Unmixing ◽  
Tissue Mass ◽  
Nirf Imaging ◽  
Obesity And Diabetes ◽  
Brown Adipose

Recent large-scale clinical analysis indicates that brown adipose tissue (BAT) mass levels inversely correlate with body-mass index (BMI), suggesting that BAT is associated with metabolic disorders such as obesity and diabetes. PET imaging with 18F-FDG is the most commonly used method for visualizing BAT. However, this method is not able to differentiate between BAT mass and BAT activation. This task, in fact, presents a tremendous challenge with no currently existing methods to separate BAT mass and BAT activation. Our previous results indicated that BAT could be successfully imaged in mice with near infrared fluorescent (NIRF) curcumin analogues. However, the results from conventional NIRF imaging could not reflect what portion of the NIRF signal from BAT activation contributed to the signal observed. To solve this problem, we used spectral unmixing to separate/unmix NIRF signal from oil droplets in BAT, which represents its mass and NIRF signal from blood, which represents BAT activation. In this report, results from our proof-of-concept investigation demonstrated that spectral unmixing could be used to separate NIRF signal from BAT mass and BAT activation.

scholarly journals Correlation of Plasma Amino Acid and Anthropometric Profiles with Brown Adipose Tissue Density in Humans

2021 ◽  
Vol 10 (11) ◽  
pp. 2339
Author(s):  
Miyuki Kuroiwa ◽  
Sayuri Hamaoka-Fuse ◽  
Masahiro Sugimoto ◽  
Yuko Kurosawa ◽  
Yasuko Aita ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Amino Acid ◽  
Brown Adipose Tissue ◽  
Near Infrared ◽  
Winter Season ◽  
Plasma Amino Acid ◽  
Anthropometric Parameters ◽  
Tissue Density ◽  
Brown Adipose ◽  
Branched Chain

This study examined the relationship between plasma amino acid (AA) concentrations, including branched-chain AAs, and brown adipose tissue density (BAT-d). One hundred and seventy-three subjects (69 men, 104 women) aged 22–68 years were recruited during the winter season. AAs were comprehensively quantified using liquid chromatography-time-of-flight-mass spectrometry. The total hemoglobin concentration in the supraclavicular region ([total-Hb]sup), an indicator of BAT-d, was assessed using near-infrared time-resolved spectroscopy. Anthropometric parameters, including age, percentage of body fat, and visceral fat, were evaluated. Factors associated with higher (≥74 µM) or lower (<74 µM) [total-Hb]sup were investigated by multiple logistic regression models that included AA concentrations alone (model 1) or AA concentrations and anthropometric parameters (model 2) as independent variables. When adjusted for the false discovery rate, [total-Hb]sup was positively correlated with glycine and asparagine levels in men and with the serine level in both men and women and was negatively correlated with the branched-chain AA concentration in men. Models 1 and 2 correlated with higher or lower BAT-d for men (r = 0.73, p = 0.015) and women (r = 0.58, p = 0.079) and for men (r = 0.82, p = 0.0070) and women (r = 0.70, p = 0.020), respectively. A combination of anthropometric parameters and plasma AA concentrations could be a reliable biomarker for higher and lower BAT-d.

Effects of fasting and food restriction on brown adipose tissue composition in normal and dystrophic hamsters

1986 ◽  
Vol 64 (7) ◽  
pp. 970-975 ◽  
Author(s):  
M. Desautels ◽  
R. A. Dulos ◽  
H. M. Yuen
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Food Deprivation ◽  
Food Restriction ◽  
Tissue Mass ◽  
Tissue Protein ◽  
Guanosine Diphosphate ◽  
Isolated Mitochondria ◽  
Daily Food ◽  
Brown Adipose

Fasting for 36–48 h or food restriction (30% reduction of daily food intake for 6 weeks) caused brown adipose tissue (BAT) atrophy in hamsters. Fasting-induced atrophy was characterized by reductions in tissue mass, DNA, protein, and thermogenin. By contrast, food restriction had no effect on tissue cellularity (DNA) but markedly reduced the tissue protein and thermogenin contents. The concentration of thermogenin in isolated mitochondria was unchanged by fasting or food restriction. Dystrophic hamsters had a reduced BAT mass when compared with weight-matched control hamsters. This resulted from a reduction in tissue cellularity since BAT DNA, protein and thermogenin contents were all reduced. The extent of binding of [3H]guanosine diphosphate to isolated mitochondria and their content of thermogenin were similar in normal and dystrophic hamsters. In response to cold exposure, as in normal hamsters, BAT of dystrophic hamsters grew and the tissue thermogenin increased, but the mitochondrial concentration of thermogenin did not change. In response to fasting, in contrast with normal hamsters, there was no significant reduction in BAT DNA in dystrophic animals and the loss of tissue protein was reduced. However, the relative changes in BAT composition during chronic food restriction were similar in normal and dystrophic animals. Thus, reduction in hamster BAT thermogenic capacity during food deprivation may occur by loss of cells and (or) reduction in the tissue protein and thermogenin contents. The extent of protein and (or) DNA loss may be dependent upon the original tissue mass and the severity of food deprivation.

scholarly journals Brown adipose tissue density measured by near-infrared time-resolved spectroscopy in Japanese, across a wide age range

2018 ◽  
Vol 23 (06) ◽  
pp. 1 ◽  
Author(s):  
Sayuri Fuse ◽  
Shinsuke Nirengi ◽  
Shiho Amagasa ◽  
Toshiyuki Homma ◽  
Ryotaro Kime ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Near Infrared ◽  
Time Resolved ◽  
Time Resolved Spectroscopy ◽  
Tissue Density ◽  
Brown Adipose ◽  
Age Range

Caloric Restriction Paradoxically Increases Adiposity in Mice With Genetically Reduced Insulin

Endocrinology ◽  
2016 ◽  
Vol 157 (7) ◽  
pp. 2724-2734 ◽  
Author(s):  
Derek A. Dionne ◽  
Søs Skovsø ◽  
Nicole M. Templeman ◽  
Susanne M. Clee ◽  
James D. Johnson
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Caloric Restriction ◽  
Gene Dosage ◽  
Tissue Growth ◽  
Tissue Mass ◽  
Brown Adipose ◽  
Paradoxical Effects ◽  
Plasma Insulin Levels ◽  
Ad Libitum

Antiadiposity effects of caloric restriction (CR) are associated with reduced insulin/IGF-1 signaling, but it is unclear whether the effects of CR would be additive to genetically reducing circulating insulin. To address this question, we examined female Ins1+/−:Ins2−/− mice and Ins1+/+:Ins2−/− littermate controls on either an ad libitum or 60% CR diet. Although Igf1 levels declined as expected, CR was unable to reduce plasma insulin levels in either genotype below their ad libitum-fed littermate controls. In fact, 53-week-old Ins1+/−:Ins2−/− mice exhibited a paradoxical increase in circulating insulin in the CR group compared with the ad libitum-fed Ins1+/−:Ins2−/− mice. Regardless of insulin gene dosage, CR mice had lower fasting glucose and improved glucose tolerance. Although body mass and lean mass predictably fell after CR initiation, we observed a significant and unexpected increase in fat mass in the CR Ins1+/−:Ins2−/− mice. Specifically, inguinal fat was significantly increased by CR at 66 weeks and 106 weeks. By 106 weeks, brown adipose tissue mass was also significantly increased by CR in both Ins1+/−:Ins2−/− and Ins1+/+:Ins2−/− mice. Interestingly, we observed a clear whitening of brown adipose tissue in the CR groups. Mice in the CR group had altered daily energy expenditure and respiratory exchange ratio circadian rhythms in both genotypes. Multiplexed analysis of circulating hormones revealed that CR was associated with increased fasting and fed levels of the obesogenic hormone, glucose-dependent insulinotropic polypeptide. Collectively these data demonstrate CR has paradoxical effects on adipose tissue growth in the context of genetically reduced insulin.

scholarly journals Dopamine receptor D1- and D2-agonists do not spark brown adipose tissue thermogenesis in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Francesca-Maria Raffaelli ◽  
Julia Resch ◽  
Rebecca Oelkrug ◽  
K. Alexander Iwen ◽  
Jens Mittag
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Dopamine Receptor ◽  
Ex Vivo ◽  
Potential Target ◽  
D2 Agonist ◽  
Obesity And Diabetes ◽  
Brown Adipose

AbstractBrown adipose tissue (BAT) thermogenesis is considered a potential target for treatment of obesity and diabetes. In vitro data suggest dopamine receptor signaling as a promising approach; however, the biological relevance of dopamine receptors in the direct activation of BAT thermogenesis in vivo remains unclear. We investigated BAT thermogenesis in vivo in mice using peripheral administration of D1-agonist SKF38393 or D2-agonist Sumanirole, infrared thermography, and in-depth molecular analyses of potential target tissues; and ex vivo in BAT explants to identify direct effects on key thermogenic markers. Acute in vivo treatment with the D1- or D2-agonist caused a short spike or brief decrease in BAT temperature, respectively. However, repeated daily administration did not induce lasting effects on BAT thermogenesis. Likewise, neither agonist directly affected Ucp1 or Dio2 mRNA expression in BAT explants. Taken together, the investigated agonists do not seem to exert lasting and physiologically relevant effects on BAT thermogenesis after peripheral administration, demonstrating that D1- and D2-receptors in iBAT are unlikely to constitute targets for obesity treatment via BAT activation.

scholarly journals Multimodal Imaging for the Detection of Brown Adipose Tissue Activation in Women: A Pilot Study Using NIRS and Infrared Thermography

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Valentina Hartwig ◽  
Letizia Guiducci ◽  
Martina Marinelli ◽  
Laura Pistoia ◽  
Tommaso Minutoli Tegrimi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Pilot Study ◽  
Brown Adipose Tissue ◽  
Infrared Thermography ◽  
Pharmacological Intervention ◽  
Oral Glucose ◽  
Cold Stimulation ◽  
Standard Clinical Practice ◽  
Obesity And Diabetes ◽  
Brown Adipose

Purpose. A clear link between obesity and brown adipose tissue (BAT) dysfunction has been recently demonstrated. The purpose of this pilot study is to determine if near-infrared spectroscopy (NIRS) 2D imaging together with infrared thermography (IRT) is capable of identifying thermal and vascular response in the supraclavicular (SCV) areas after the ingestion of an oral glucose load as a thermogenic stimulation. Method. We studied two groups of women (obese versus lean) for discerning their different responses. NIRS and IRT images were acquired on the neck in the left SCV region during a 3 h oral glucose tolerance test (OGTT) and immediately after a cold stimulation. Results. We detected a significant thermal response of BAT in SCV fossa in both groups. Both during OGTT and after cold stimulation, skin temperature was persistently higher in lean versus obese. This response was not coupled with changes in oxygen saturation of subcutaneous tissue in that area. Discussion and Conclusion. The results show that NIRS/IRT may be a novel, noninvasive, radiation-free, easy to use, and low-cost method for monitoring, during the standard clinical practice, the diet and pharmacological intervention which aims to stimulate BAT as a potential therapeutic target against obesity and diabetes.

scholarly journals Synthesis-free PET imaging of brown adipose tissue and TSPO via Combination of Disulfiram and 64CuCl2

2017 ◽  
Author(s):  
Jing Yang ◽  
Jian Yang ◽  
Lu Wang ◽  
Anna Moore ◽  
Steven H. Liang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Pet Imaging ◽  
Imaging Biomarker ◽  
Imaging Method ◽  
Steroid Synthesis ◽  
Pet Tracer ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
First Time

AbstractPET imaging is a widely applicable but a very expensive technology. Strategies that can significantly reduce the high cost of PET imaging are highly desirable both for research and commercialization. On-site synthesis is one important contributor to the high cost. In this report, we demonstrated the feasibility of a synthesis-free method for PET imaging of brown adipose tissue (BAT) and translocator protein 18kDa (TSPO) via a combination of Disulfiram, an FDA approved drug for alcoholism, and 64CuCl2 (termed 64Cu-Dis). Our blocking studies, Western blot, and tissue histological imaging suggested that the observed BAT contrast was due to 64Cu-Dis binding to TSPO, which was further confirmed as a specific biomarker for BAT imaging using [18F]-F-DPA, a TSPO-specific PET tracer. Our studies, for the first time, demonstrated that TSPO could serve as a potential imaging biomarker for BAT. Furthermore, since imaging contrast obtained with both 64Cu-Dis and [18F]-F-DPA was not dependent on BAT activation, these agents could be used for reliably imaging BAT mass. Additional value of our synthesis-free approach could be applied to imaging TSPO in other tissues as it is an established biomarker of neuro-inflammation in activated microglia and plays a role in immune response, steroid synthesis, and apoptosis. Although here we applied 64Cu-Dis for a synthesis-free PET imaging of BAT, we believe that our strategy could be extended to other targets while significantly reducing the cost of PET imaging.SignificanceBrown adipose tissue (BAT) has been considered as “good fat,” and large-scale analysis has undoubtedly validated its clinical significance. BAT tightly correlates with body-mass index (BMI), suggesting that BAT bears clear significance for metabolic disorders such as obesity and diabetes. BAT imaging with [18F]-FDG, the most used method for visualizing BAT, primarily reflects BAT activation, but not BAT mass. A convenient imaging method that can consistently reflect BAT mass is still lacking. In this report, we demonstrated that BAT mass can be reliably imaged with a synthesis-free method using the combination of Disulfiram and 64CuCl2 (64Cu-Dis) via TSPO binding. We further demonstrated for the first time that TSPO is a specific imaging biomarker for BAT.

scholarly journals ACE2 Pathway Regulates Thermogenesis and Energy Metabolism

2021 ◽  
Author(s):  
Xi Cao ◽  
Tingting Shi ◽  
Chuanhai Zhang ◽  
Wanzhu Jin ◽  
Lini Song ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Knockout Mice ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Cold Stimulation ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
Pka Pathway

Identification of key regulators of energy homeostasis holds important therapeutic promise for metabolic disorders, such as obesity and diabetes. ACE2 cleaves angiotensin II (Ang II) to generate Ang-(1-7) which acts mainly through the Mas receptor. Here, we identify ACE2 pathway as a critical regulator in the maintenance of thermogenesis and energy expenditure. We found that ACE2 is highly expressed in brown adipose tissue (BAT) and that cold stimulation increases ACE2 and Ang-(1-7) levels in BAT and serum. ACE2 knockout mice (ACE2-/y), Mas knockout mice (Mas-/-), and the mice transplanted with brown adipose tissue from Mas-/- mice displayed impaired thermogenesis. In contrast, impaired thermogenesis of db/db obese diabetic mice and high-fat diet-induced obese mice were ameliorated by overexpression of ACE2 or continuous infusion of Ang-(1-7). Activation of ACE2 pathway was associated with improvement of metabolic parameters, including blood glucose, lipids and energy expenditure in multiple animal models. Consistently, ACE2 pathway remarkably enhanced the browning of white adipose tissue. Mechanistically, we showed that ACE2 pathway activated Akt/FoxO1 and PKA pathway, leading to induction of UCP1 and activation of mitochondrial function. Our data propose that adaptive thermogenesis requires regulation of ACE2 pathway and highlight novel therapeutic targets for the treatment of metabolic disorders.

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