Brown Adipose Tissue Uptake Research Articles

FDG Uptake in Brown Adipose Tissue Activated by a Long-Acting β2-Adrenergic Receptor Agonist Inhaler Prescribed for Bronchial Asthma.

We herein report a case of an elderly woman in whom brown adipose tissue (BAT) was visible on 18 F-FDG PET imaging performed in the summer. In this patient, none of the well-known factors that induce BAT activation in adults, including cold exposure, catecholamine-producing tumors, or β3-adrenergic receptor agonists administration, were present. Daily inhalation of a long-acting β2-adrenergic agonist for treatment of her bronchial asthma was considered the cause of her BAT visualization. This case suggests the need to consider β2-adrenergic receptor agonists as a cause of BAT visualization.

Iodine-131 Metaiodobenzylguanidine (MIBG) and NP-59 uptakes in the Rat Normal Tissues: Increase of Cholesterol uptake in Cold-Activated Brown Adipose Tissue

Objective Aim: NP-59 (I-131-6ß-iodomethyl-19-norcholesterol) and MIBG (I-131-metaiodobenzylguanidine) both are useful to detect tumors. There is a great need to understand their distributions in normal organs and tissues as well as ways to reduce normal uptakes in tumor imaging and/or treatment. Activated Brown Adipose tissue (BAT) has been promising for its role in optimal treatment of obesity and hypercholesterolemia. The study of cholesterol uptake in BAT may have a significant impact in managing hyperlipidemia and protecting from atherosclerosis. Materials and Methods: Male Sprague-Dawley rats weighing 250—300 g were used in the study. All animals received 25 µCi of I-131-MIBG or NP-59 by the tail vein and were killed (N = 4 - 6 each) 3, 24 or 48 hours afterwards. For cold stressed animals were kept at 6 – 8 C in a cold room overnight prior to receiving labeled MIBG or NP-59. The animal continued to stay in cold room as compared to room temperature controls. To study the effect of norepinephrine-blocking agent, reserpine (4 mg/kg, IP) was given to rats 4 hours prior to I-131-MIBG infusion. Organs were immediately dissected. Radioactivity was counted and tissue concentrations were expressed as percent kilogram (body weight) dose per gram of tissue (% Kg dose/g). Findings: Higher uptakes of I-131-MIBG were observed in organs rich in sympathetic innervation [BAT (brown adipose tissue), heart and spleen] as compared to liver and muscle. Reserpine reduced uptakes in BAT, heart, adrenals and spleen but not in liver in room temperature controls. BAT, but not in other organs, showed a paradoxical increase in reserpine-treated animal kept in cold room as compared to room temperature controls. NP-59 showed a near 6 folds increase in adrenals from 30 minutes to 48 hours and unchanged in cold stressed animals. The only tissue showed significant increases in NP-59 uptake under cold stress was BAT from 1.84 folds at 30 minutes to 1.44 folds at 48 hours (p<0.05 as compared to room temperature controls). Conclusions: The uptake of MIBG is reduced in organs rich in sympathetic innervation under cold stress, but this reduction is partially blocked by reserpine. Findings may help to improve the efficacy of MIBG as a theragnostic agent. A noteworthy finding is the significant increase in NP-59, a cholesterol analog, in cold-activated BAT. This novel observation could serve as a valuable tool for studying the role of activated BAT in the overall cholesterol metabolism in humans. Furthermore, it presents a potent therapeutic avenue for mitigating hyperlipidemia and providing protection against atherosclerosis.

An efficient AAV vector system of Rec2 serotype for intravenous injection to study metabolism in brown adipocytes in vivo

ObjectiveRecombinant adeno-associated virus (rAAV) vectors are powerful tools for the sustained expression of proteins in vivo and have been successfully used for mechanistic studies in mice. A major challenge associated with this method is to obtain tissue specificity and high expression levels without need of local virus administration. MethodsTo achieve this goal for brown adipose tissue (BAT), we developed a rAAV vector for intravenous bolus injection, which includes an expression cassette comprising an uncoupling protein-1 enhancer-promoter for transcription in brown adipocytes and miR122 target sequences for suppression of expression in the liver, combined with packaging in serotype Rec2 capsid protein. To test tissue specificity, we used a version of this vector expressing Cre recombinase to transduce mice with floxed alleles to knock out MLXIPL (ChREBP) or tdTomato-Cre reporter mice. ResultsWe demonstrated efficient Cre-dependent recombination in interscapular BAT and variable effects in minor BAT depots, but little or no efficacy in white adipose tissues, liver and other organs. Direct overexpression of glucose transporter SLC2A1 (GLUT1) using the rAAV vector in wild type mice resulted in increased glucose uptake and glucose-dependent gene expression in BAT, indicating usefulness of this vector to increase the function even of abundant proteins. ConclusionTaken together, we describe a novel brown adipocyte-specific rAAV method to express proteins for loss-of-function and gain-of-function metabolic studies. The approach will enable researchers to access brown fat swiftly, reduce animal breeding time and costs, as well as enable the creation of new transgenic mouse models combining multiple transgenes.

Monocarboxylate transporters facilitate succinate uptake into brown adipocytes.

Uptake of circulating succinate by brown adipose tissue (BAT) and beige fat elevates whole-body energy expenditure, counteracts obesity and antagonizes systemic tissue inflammation in mice. The plasma membrane transporters that facilitate succinate uptake in these adipocytes remain undefined. Here we elucidate a mechanism underlying succinate import into BAT via monocarboxylate transporters (MCTs). We show that succinate transport is strongly dependent on the proportion that is present in the monocarboxylate form. MCTs facilitate monocarboxylate succinate uptake, which is promoted by alkalinization of the cytosol driven by adrenoreceptor stimulation. In brown adipocytes, we show that MCT1 primarily facilitates succinate import. In male mice, we show that both acute pharmacological inhibition of MCT1 and congenital depletion of MCT1 decrease succinate uptake into BAT and consequent catabolism. In sum, we define a mechanism of succinate uptake in BAT that underlies its protective activity in mouse models of metabolic disease.

Incidence and Risk Factors for Brown Adipose Tissue Uptake in PET Imaging in Pediatric Patients.

Positron emission tomography (PET) scans are used in disease diagnosis and evaluation for pediatric oncology patients. Brown adipose tissue (BAT) 18 F-fluorodeoxyglucose-PET uptake is reported in 35% to 47% of pediatric patients. Several risk factors may be associated with BAT uptake. The aim was to determine the incidence and risk factors for BAT in pediatric patients using a consensus-based system and a novel grading scale. A total of 285 PET scans in 154 patients were retrospectively reviewed for the presence of BAT from September 2015 through December 2016. A consensus review was done by 2 radiologists, who graded BAT on a 0 to 3 scale and assessed its impact on PET interpretation. The presence of moderate to severe BAT occurred in 11% of PET scans, and 6% of PETs had limited interpretation. Hodgkin lymphoma (n=53) patients had a 3.62-fold increased odds of moderate or severe BAT and a 6.59-fold increased odds of limited interpretation on PET imaging. The incidence of BAT was low but impacted radiologic interpretation when present. Further studies with a larger group of Hodgkin lymphoma patients are needed to explore the risk factors associated with moderate or severe BAT.

Physiologic 18F-FDG Uptake in Brown Adipose Tissue and Lactating Breast in a Patient with Hodgkin Lymphoma.

We present the case of a young woman with Hodgkin lymphoma exhibiting physiologic 18F-FDG uptake in brown adipose tissue and lactating breast on consecutive 18F-FDG PET/CT scans. Both entities are common imaging interpretation pitfalls and should be recognized in oncologic 18F-FDG PET/CT practice. We review the imaging features and differential diagnosis of these 2 entities and discuss the radiation safety precautions during breastfeeding.

Changes in plasma endocannabinoids concentrations correlate with 18F-FDG PET/MR uptake in brown adipocytes in humans.

Introduction: Recent data suggest a possible role of endocannabinoids in the regulation of brown adipose tissue (BAT) activity. Those findings indicate potential treatment options for obesity. The aim of this study was to evaluate the relationship between plasma endocannabinoids concentrations and the presence of BAT in humans. Methods: The study group consisted of 25 subjects divided into two groups: BAT positive BAT(+), (n = 17, median age = 25years) and BAT negative BAT(-), (n = 8, median age = 28years). BAT was estimated using 18F-FDG PET/MR after 2h of cold exposure. The level of plasma endocannabinoids was assessed at baseline, 60min and 120min of cold exposure. Results: In both groups, BAT(+) and BAT(-), during the cooling, we observed a decrease of the same endocannabinoids: arachidonoylethanolamide (AEA), eicosapentaenoyl ethanolamide (EPEA) and oleoyl ethanolamide (OEA) with a much more profound decline in BAT(+) subjects. Statistically significant fall of PEA (palmitoylethanolamide) and SEA (stearoylethanolamide) concentrations after 60min (FC = 0.7, p = 0.007 and FC = 0.8, p = 0.03, respectively) and 120min (FC = 0.81, p = 0.004, and FC = 0.9, p = 0.01, respectively) of cooling was observed only in individuals with BAT. Conclusion: We noticed the profound decline of endocannabinoids concentrations in subjects with increased 18F-FDG PET/MR uptake in BAT. Identification of a new molecules related to BAT activity may create a new target for obesity treatment.

MiR-143 targets SYK to regulate NEFA uptake and contribute to thermogenesis in male mice.

Excessive energy intake is the main cause of obesity, and stimulation of brown adipose tissue (BAT) and white adipose tissue (WAT) thermogenesis has emerged as an attractive tool for anti-obesity. Although miR-143 has been reported to be associated with BAT thermogenesis, its role remains unclear. Here, we found that miR-143 was highest expression in adipose tissue, especially in BAT. During short-term cold exposure or CL316,243 injected, miR-143 was markedly down-regulated in BAT and subcutaneous WAT (scWAT). Moreover, knockout of miR-143 (KO) increases the body temperature of mice upon cold exposure, which may be due to the increased thermogenesis of BAT and scWAT. More importantly, supplement of miR-143 in BAT of KO mice can inhibit the increase of body temperature in KO mice. Mechanistically, spleen tyrosine kinase (SYK) was revealed for the first time as a new target of miR-143, and deletion of miR-143 facilitates fatty acid uptake in BAT. In addition, we found that brown adipocytes can promote fat mobilization of white adipocytes, and miR-143 may participate in this process. Meanwhile, we demonstrate that inactivation of AC9 in BAT inhibits thermogenesis through AC9-PKA-AMPK-CREB-UCP1 signaling pathway. Overall, our results reveal a novel function of miR-143 on thermogenesis, and a new functional link of the BAT and WAT.

18F]FDG and [11C]PK11195 PET imaging in the evaluation of brown adipose tissue - effects of cold and pharmacological stimuli and their association with crotamine intake in a male mouse model

This study aimed to evaluate the role of positron emission tomography (PET) with [11C]PK11195 and [18F]FDG in the characterization of brown adipose tissue (BAT). MethodsMale C57BL/6 mice were studied with the glucose analogue [18F]FDG (n = 21) and the TSPO mitochondrial tracer [11C]PK11195 (n = 28), without stimulus and after cold (6–9 °C) or beta-agonist (CL316243) stimuli. PET studies were performed at baseline and after 21 days of daily treatment with crotamine, which is a peptide described to induce adipocyte tissue browning and to increase BAT metabolism. Tracer uptake (SUVmax) was measured in the interscapular BAT and translocator protein 18 kDa (TSPO) expression was evaluated by immunohistochemistry. ResultsThe cold stimulus increased [18F]FDG uptake compared to no-stimulus (5.21 ± 1.05 vs. 2.03 ± 0.21, p < 0.0001) and to beta-agonist stimulus (2.65 ± 0.39, p = 0.0003). After 21 days of treatment with crotamine, there was no significant difference in the [18F]FDG uptake compared to the baseline in the no-stimulus group and in the cold-stimulus group, with a significant increase in uptake after CL stimulus (baseline: 2.65 ± 0.39; 21 days crotamine: 4.77 ± 0.81, p = 0.0003). Evaluation of [11C]PK11195 at baseline shows that CL stimulus increases the BAT uptake compared to no-stimulus (4.47 ± 0.66 vs. 3.36 ± 0.68, p = 0.014). After 21 days of treatment with crotamine, there was no significant difference in the [11C]PK11195 uptake compared to the baseline in the no-stimulus group (2.94 ± 0.58, p = 0.7864) and also after CL stimulus (3.55 ± 0.79, p = 0.085). TSPO expression correlated with [11C]PK11195 uptake (r = 0.83, p = 0.018) but not with [18F]FDG uptake (r = 0.40, p = 0.516). Conclusions[11C]PK11195 allowed the identification of BAT under thermoneutral conditions or after beta3-adrenergic stimulation in a direct correlation with TSPO expression. The beta-adrenergic stimulus, despite presenting a lower intensity of glycolytic activation compared to cold at baseline, allowed the observation of an increase in BAT uptake of [18F]FDG after 21 days of crotamine administration. Although some limitations were observed for the metabolic changes induced by crotamine, this study reinforced the potential of using [11C]PK11195 and/or [18F]FDG-PET to monitor the activation of BAT.

Loss of transketolase promotes the anti-diabetic role of brown adipose tissues.

Transketolase (TKT), an enzyme in the non-oxidative branch of the pentose phosphate pathway (PPP), bi-directionally regulates the carbon flux between the PPP and glycolysis. Loss of TKT in adipose tissues decreased glycolysis and increased lipolysis and uncoupling protein-1 (UCP1) expression, protecting mice from high-fat diet-induced obesity. However, the role of TKT in brown adipose tissue (BAT)-dependent glucose homeostasis under normal chow diet remains to be elucidated. We found that TKT ablation increased levels of glucose transporter 4 (GLUT4), promoting glucose uptake and glycogen accumulation in BAT. Using the streptozotocin (STZ)-induced diabetic mouse model, we discovered that enhanced glucose uptake due to TKT deficiency in BAT contributed to decreasing blood glucose and weight loss, protecting mice from STZ-induced diabetes. Mechanistically, TKT deficiency decreased the level of thioredoxin-interacting protein, a known inhibitor for GLUT4, by decreasing NADPH and glutathione levels and inducing oxidative stress in BAT. Therefore, our data reveal a new role of TKT in regulating the anti-diabetic function of BAT as well as glucose homeostasis.

Secretin modulates appetite via brown adipose tissue-brain axis

PurposeSecretin activates brown adipose tissue (BAT) and induces satiation in both mice and humans. However, the exact brain mechanism of this satiety inducing, secretin-mediated gut-BAT-brain axis is largely unknown.Methods and resultsIn this placebo-controlled, single-blinded neuroimaging study, firstly using [18F]-fluorodeoxyglucose (FDG) PET measures (n = 15), we established that secretin modulated brain glucose consumption through the BAT-brain axis. Predominantly, we found that BAT and caudate glucose uptake levels were negatively correlated (r = -0.54, p = 0.037) during secretin but not placebo condition. Then, using functional magnetic resonance imaging (fMRI; n = 14), we found that secretin improved inhibitory control and downregulated the brain response to appetizing food images. Finally, in a PET-fMRI fusion analysis (n = 10), we disclosed the patterned correspondence between caudate glucose uptake and neuroactivity to reward and inhibition, showing that the secretin-induced neurometabolic coupling patterns promoted satiation.ConclusionThese findings suggest that secretin may modulate the BAT-brain metabolic crosstalk and subsequently the neurometabolic coupling to induce satiation. The study advances our understanding of the secretin signaling in motivated eating behavior and highlights the potential role of secretin in treating eating disorders and obesity.Trial registrationEudraCT no. 2016-002373-35, registered 2 June 2016; Clinical Trials no. NCT03290846, registered 25 September 2017.

VLDL-VLDLR axis facilitates brown fat thermogenesis through replenishment of lipid fuels and PPARβ/δ activation

In mammals, brown adipose tissue (BAT) is specialized to conduct non-shivering thermogenesis for survival under cold acclimation. Although emerging evidence suggests that lipid metabolites are essential for heat generation in cold-activated BAT, the underlying mechanisms of lipid uptake in BAT have not been thoroughly understood. Here, we show that very-low-density lipoprotein (VLDL) uptaken by VLDL receptor (VLDLR) plays important roles in thermogenic execution in BAT. Compared with wild-type mice, VLDLR knockout mice exhibit impaired thermogenic features. Mechanistically, VLDLR-mediated VLDL uptake provides energy sources for mitochondrial oxidation via lysosomal processing, subsequently enhancing thermogenic activity in brown adipocytes. Moreover, the VLDL-VLDLR axis potentiates peroxisome proliferator activated receptor (PPAR)β/δ activity with thermogenic gene expression in BAT. Accordingly, VLDL-induced thermogenic capacity is attenuated in brown-adipocyte-specific PPARβ/δ knockout mice. Collectively, these data suggest that the VLDL-VLDLR axis in brown adipocytes is a key factor for thermogenic execution during cold exposure.

NanoSPECT imaging reveals the uptake of 123I-labelled oxidized low-density lipoprotein in the brown adipose tissue of mice via CD36.

The liver is the major organ shown to remove oxidized low-density lipoprotein (oxLDL) from the circulation. Given increased evidence that thermogenic adipose tissue has anti-effects, we used 123I-labelled oxLDL as a tracer to reveal oxLDL accumulation in the brown adipose tissue (BAT) of mice. We also explored the mechanisms of oxLDL accumulation in BAT. We used high-resolution nanoSPECT/CT to investigate the tissue distribution of 123I-oxLDL and 123I-LDL (control) following intravenous injection into conscious mice. 123I-oxLDL distribution was discovered in BAT at an intensity equivalent to that in the liver, whereas 123I-LDL was detected mostly in the liver. Consistent with the function of BAT related to sympathetic nerve activity, administering anaesthesia in mice almost completely eliminated the accumulation of 123I-oxLDL in BAT, and this effect was reversed by administering β3-agonist. Furthermore, exposing mice to cold stress at 4°C enhanced 123I-oxLDL accumulation in BAT. Because in 123I-oxLDL, the protein of oxLDL was labelled, we performed additional experiments with DiI-oxLDL in which the lipid phase of oxLDL was fluorescently labelled and observed similar results, suggesting that the whole oxLDL particle was taken up by BAT. To identify the receptor responsible for oxLDL uptake in BAT, we analysed the expression of known oxLDL receptors (e.g. SR-A, CD36, and LOX-1) in cultured brown adipocyte cell line and primary brown adipocytes and found that CD36 was the major receptor expressed. Treatment of cells with CD36 siRNA or CD36 neutralizing antibody significantly inhibited DiI-oxLDL uptake. Finally, CD36 deletion in mice abolished the accumulation of 123I-oxLDL and DiI-oxLDL in BAT, indicating that CD36 is the major receptor for oxLDL in BAT. We show novel evidence for the CD36-mediated accumulation of oxLDL in BAT, suggesting that BAT may exert its anti-atherogenic effects by removing atherogenic LDL from the circulation.

Fecal microbiota composition is related to brown adipose tissue 18F-fluorodeoxyglucose uptake in young adults

ObjectiveHuman brown adipose tissue (BAT) has gained considerable attention as a potential therapeutic target for obesity and its related cardiometabolic diseases; however, whether the gut microbiota might be an efficient stimulus to activate BAT metabolism remains to be ascertained. We aimed to investigate the association of fecal microbiota composition with BAT volume and activity and mean radiodensity in young adults.Methods82 young adults (58 women, 21.8 ± 2.2 years old) participated in this cross-sectional study. DNA was extracted from fecal samples and 16S rRNA sequencing was performed to analyse the fecal microbiota composition. BAT was determined via a static 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography scan (PET/CT) after a 2 h personalized cooling protocol. 18F-FDG uptake was also quantified in white adipose tissue (WAT) and skeletal muscles.ResultsThe relative abundance of Akkermansia, Lachnospiraceae sp. and Ruminococcus genera was negatively correlated with BAT volume, BAT SUVmean and BAT SUVpeak (all rho ≤ − 0.232, P ≤ 0.027), whereas the relative abundance of Bifidobacterium genus was positively correlated with BAT SUVmean and BAT SUVpeak (all rho ≥ 0.262, P ≤ 0.012). On the other hand, the relative abundance of Sutterellaceae and Bifidobacteriaceae families was positively correlated with 18F-FDG uptake by WAT and skeletal muscles (all rho ≥ 0.213, P ≤ 0.042). All the analyses were adjusted for the PET/CT scan date as a proxy of seasonality.ConclusionOur results suggest that fecal microbiota composition is involved in the regulation of BAT and glucose uptake by other tissues in young adults. Further studies are needed to confirm these findings.Clinical trial informationClinicalTrials.gov no. NCT02365129 (registered 18 February 2015).

Increased 68Ga-DOTATATE Uptake in Supraclavicular Brown Adipose Tissue.

Characterization of brown adipose tissue (BAT) 18F-FDG uptake has been well reported; however, 68Ga-DOTA-conjugated somatostatin receptor targeting peptides uptake in BAT is rarely documented. Herein, we report an interesting case of increased 68Ga-DOTATATE uptake in supraclavicular BAT in a young boy with paroxysmal hypertension. The low body mass index and increased perfusion of BAT in response to cold may be significant influencing factors.

Different Protein Sources Enhance 18FDG-PET/MR Uptake of Brown Adipocytes in Male Subjects.

Background: The unique ability of brown adipocytes to increase metabolic rate suggests that they could be targeted as an obesity treatment. Objective: The objective of the study was to search for new dietary factors that may enhance brown adipose tissue (BAT) activity. Methods: The study group comprised 28 healthy non-smoking males, aged 21–42 years old. All volunteers underwent a physical examination and a 75 g oral glucose tolerance test (75g-OGTT). Serum atrial and brain natriuretic peptide (ANP, BNP), PRD1-BF1-RIZ1 homologous domain containing 16 (PRDM16) and eukaryotic translation initiation factor 4E (eIF4E) measurements were taken, and 3-day food intake diaries were completed. Body composition measurements were assessed using dual-energy X-ray absorptiometry (DXA) scanning and bioimpedance methods. An fluorodeoxyglucose-18 (FDG-18) uptake in BAT was assessed by positron emission tomography/magnetic resonance (PET/MR) in all participants after 2 h cold exposure. The results were adjusted for age, daily energy intake, and DXA lean mass. Results: Subjects with detectable BAT (BAT(+)) were characterized by a higher percentage of energy obtained from dietary protein and fat and higher muscle mass (p = 0.01, p = 0.02 and p = 0.04, respectively). In the BAT(+) group, animal protein intake was positively associated (p= 0.04), whereas the plant protein intake negatively correlated with BAT activity (p = 0.03). Additionally, the presence of BAT was inversely associated with BNP concentration in the 2 h of cold exposure (p = 0.002). Conclusion: The outcomes of our study suggest that different macronutrient consumption may be a new way to modulate BAT activity leading to weight reduction.

18F-FDG Uptake in Brown Adipose Tissue After Exposure to the Cold: From Possible Pitfall in Early PET Scans to Metabolic Biomarker.

There are 3 types of fat in the human body: white, brown, and beige ([1][1]). White adipocytes deposit extra energy into triglycerides, whereas beige and brown adipocytes have the unique ability to convert mitochondrial energy into heat (rather than adenosine triphosphate) via uncoupling protein 1.

18F-Fluorodeoksiglukoz positron emisyon tomografi/bilgisayarlı tomografi’de kahverengi yağ dokusu aktivitesi ve kanser durumunun korelasyonu

Aim: In this study, we aimed to compare brown adipose tissue (BAT) activity on 18F-Flourodeoxyglucose Positron Emission Tomography (PET)/Computed Tomography(CT) in patients with and without active cancer. &#x0D; Material and Methods: Results of the patients who underwent 18F-FDG PET/CT between January 2014 and February 2018 in Nuclear Medicine Department were evaluated retrospectively. Age, gender, body mass index (BMI), serum levels of glucose, bilirubin, total cholesterol (T-chol), low-density lipoprotein (LDL) and triglyceride (TG) of the patients were noted from the hospital database. Mean outdoor temperature of the day during PET/CT imaging was searched from National Weather Service archives. Diagnosis and disease activity status on PET/CT imaging were evaluated retrospectively. Standardized uptake value (SUV) and brown adipose tissue volume (BAV) were calculated on PET/CT images. Additionally, hepatic attenuation index and subcutaneous adipose tissue thickness (SCATT) were calculated from CT images. Difference between median SUV and BAV among groups with and without active cancer was analyzed. &#x0D; Results: Totally 78 (54 F; 24 M; mean age 34.415.6) patients who underwent 18F-FDG PET/CT for different oncological indications were included in the analysis. All the patients had different degrees of BAT uptake on PET/CT images. Median (min-max) values for SUV, BAV and SCATT were found as 8.0 (2.7-37.0), 26.9 (2.1- 116.0) cm3 and 15.0 (3.0- 46.0) mm, respectively. Hepatic attenuation index was 0-5%, 6-30% and &gt;30% in 56 (71%), 20 (26%) and 2 (3%) patients, respectively. Active disease was observed in 26 (33%) patients during PET/CT imaging. In the evaluation of the distribution of the adipose tissue parameters, median SUV (p=0.008) and BAV (p=0.008) of groups with and without active cancer were found statistically significant. &#x0D; Conclusion: BAT activity in patients with active cancer seems to be higher than that in patients without active disease, supporting the possible role of adipose tissue activation on cancer development and progression.

Brown adipose tissue is the key depot for glucose clearance in microbiota depleted mice

Gut microbiota deficient mice demonstrate accelerated glucose clearance. However, which tissues are responsible for the upregulated glucose uptake remains unresolved, with different studies suggesting that browning of white adipose tissue, or modulated hepatic gluconeogenesis, may be related to enhanced glucose clearance when the gut microbiota is absent. Here, we investigate glucose uptake in 22 different tissues in 3 different mouse models. We find that gut microbiota depletion via treatment with antibiotic cocktails (ABX) promotes glucose uptake in brown adipose tissue (BAT) and cecum. Nevertheless, the adaptive thermogenesis and the expression of uncoupling protein 1 (UCP1) are dispensable for the increased glucose uptake and clearance. Deletion of Ucp1 expressing cells blunts the improvement of glucose clearance in ABX-treated mice. Our results indicate that BAT and cecum, but not white adipose tissue (WAT) or liver, contribute to the glucose uptake in the gut microbiota depleted mouse model and this response is dissociated from adaptive thermogenesis.

Perspectives on Brown Adipose Tissue Imaging: Insights from Preclinical and Clinical Observations from the Last and Current Century.

Brown adipose tissue (BAT) was first described in the 16th century, but until late last century had mainly been considered a tissue with the function of nonshivering thermogenesis, maintaining body temperature in key organs in newborns who have high body surface areas relative to their weight and thus marked radiative heat loss. BAT was believed to have substantially disappeared by adulthood. Molecular imaging with 18F-FDG PET and PET combined with CT, as well as imaging with 131I-metaiodobenzylguanidine (MIBG) beginning late last century have shown BAT to be present and active well into adulthood. This review highlights key aspects of BAT biology, early empiric observations misidentifying BAT, pitfalls in image interpretation, and methods to intentionally reduce BAT uptake, and outlines multiple imaging methods used to identify BAT invivo. The therapeutic potential of increasing the amount or activity of BAT for weight loss and improvement of glucose and lipid profiles is highlighted as a major opportunity. Molecular imaging can help dissect the physiology of this complex dynamic tissue and offers the potential for addressing challenges separating "active BAT" from "total BAT." Research in BAT has grown extensively, and 18F-FDG PET is the key imaging procedure against which all other BAT imaging methods must be compared. Given the multiple functions of BAT, it is reasonable to consider it a previously unrecognized endocrine tissue and thus an appropriate topic for review in this supplement to The Journal of Nuclear Medicine.