A comprehensive morphometric study of visceral and subcutaneous adipose tissue depots in mice, hamsters and rats / Un estudio morfométrico completo de los depósitos de tejido adiposo visceral y subcutáneo en ratones, hámsters y ratas

SUMMARY: Adipose tissue morphology of different fat tissue depots can be described using the number of adipocytes and cell surface of adipocytes. This study deals with characteristics and morphometric analysis of white and brown adipose tissue depots in healthy adult laboratory mice, hamsters and rats of both sexes. The number of unilocular adipocytes in white adipose tissue differs from one adipose tissue depot to another, with the largest number of adipocytes in mice and a similar number in hamsters and rats. The smallest surface area and the largest percentage of small unilocular adipocytes were found in mice. White adipose tissue in hamsters and rats was predominantly made out of a larger percentage of medium-sized adipocytes and a smaller percentage of small and medium-sized adipocytes. Uncoupling protein 1 positive multilocular adipocytes were found in classic brown adipose tissue depots with larger percentages in mice (93.20 %) and hamsters (91.30 %), while rats had a smaller percentage (78.10 %). In white and brown adipose tissue, significant differences between species and both sexes within the same species were found, indicating the influence of sexual dimorphism. The presented morphometric results could serve as a basis for further studies concerning experimental animal models of metabolic disorders and obesity.

RESUMEN: La morfología del tejido adiposo de diferentes depósitos de tejido graso se puede describir utilizando el número de adipocitos y la superficie celular de los adipocitos. Este estudio analiza las características y el análisis morfométrico de los depósitos de tejido adiposo blanco y marrón en ratones, hamsters y ratas de laboratorio, adultos sanos de ambos sexos. El número de adipocitos uniloculares en el tejido adiposo blanco difiere de un depósito de tejido adiposo a otro, con el mayor número de adipocitos en ratones y un número similar en hámsteres y ratas. La superficie más pequeña y el mayor porcentaje de adipocitos uniloculares pequeños se encontraron en ratones. El tejido adiposo blanco en hámsteres y ratas estaba compuesto predominantemente por un mayor porcentaje de adipocitos de tamaño mediano y un porcentaje menor de adipocitos de tamaño pequeño y mediano. Los adipocitos multiloculares positivos para la proteína desacopladora 1 se encontraron en depósitos de tejido adiposo marrón clásico con mayores porcentajes en ratones (93,20 %) y hámsters (91,30 %), mientras que las ratas tenían un porcentaje menor (78,10 %). En el tejido adiposo blanco y pardo se encontraron diferencias significativas entre especies y entre ambos sexos dentro de una misma especie, lo que indica la influencia del dimorfismo sexual. Los resultados morfométricos presentados podrían servir como base para futuros estudios sobre modelos animales experimentales de trastornos metabólicos y obesidad.

Mouse model of the adipose organ: the heterogeneous anatomical characteristics.

Adipose tissue plays a pivotal role in energy storage, hormone secretion, and temperature control. Mammalian adipose tissue is largely divided into white adipose tissue and brown adipose tissue, although recent studies have discovered the existence of beige adipocytes. Adipose tissues are widespread over the whole body and each location shows distinctive metabolic features. Mice are used as a representative experimental model system in metabolic studies due to their numerous advantages. Importantly, the adipose tissues of experimental animals and humans are not perfectly matched, and each adipose tissue exhibits both similar and specific characteristics. Nevertheless, the diversity and characteristics of mouse adipose tissue have not yet been comprehensively summarized. This review summarizes diverse information about the different types of adipose tissue being studied in mouse models. The types and characteristics of adipocytes were described, and each adipose tissue was classified by type, and features such as its distribution, origin, differences from humans, and metabolic characteristics were described. In particular, the distribution of widely studied adipose tissues was illustrated so that researchers can comprehensively grasp its location. Also, the adipose tissues misused or confusingly used among researchers were described. This review will provide researchers with comprehensive information and cautions needed to study adipose tissues in mouse models.

Associations Between Brain Gray Matter Volumes and Adipose Tissue Metabolism in Healthy Adults.

OBJECTIVE: Gray matter (GM) volume in different brain loci has been shown to vary in obesity and diabetes, and elevated fasting plasma nonesterified fatty acid (NEFA) levels have been suggested as one potential mechanism. The hypothesis presented in this study is that brown adipose tissue (BAT) activity may correlate with GM volume in areas negatively associated with obesity and diabetes. METHODS: A total of 36 healthy patients (M/F: 12/24, age 39.7 ± 9.4 years, BMI 27.5 ± 5.6 kg/m2 ) were imaged with positron emission tomography using fatty acid analog [18 F]FTHA to measure NEFA uptake and with [15 O]H2 O to measure perfusion during cold exposure, at room temperature during fasting, or during a postprandial state. A 2-hour hyperinsulinemic euglycemic clamp was performed to measure whole-body insulin sensitivity (M value, mean 7.6 ± 3.9 mg/kg/min). T1-weighted magnetic resonance imaging at 1.5 T was performed on all patients. RESULTS: BAT NEFA uptake was associated directly with GM volume in anterior cerebellum and occipital lobe (P ≤ 0.04) when adjusted for age, gender, and intra-abdominal fat volume and with anterior cerebellum, limbic lobe, and temporal lobe GM volumes when adjusted for M value. CONCLUSIONS: BAT NEFA metabolism may participate in protection from cognitive degeneration associated with cardiometabolic risk factors, such as central obesity and insulin resistance. Potential causal relationships between BAT activity and GM volumes remain to be examined.

Association between dietary factors and brown adipose tissue volume/18F-FDG uptake in young adults.

OBJECTIVE: To study the association between usual dietary factors (dietary energy density, nutrient intake, food group consumption, and dietary pattern) and brown adipose tissue (BAT) volume/18F-fluorodeoxyglucose (18F-FDG) uptake after personalized cold exposure in young healthy adults. METHODS: A total of 122 young adults (n = 82 women; 22.0 ± 2.1 years old; 24.8 ± 4.8 kg/m2) took part in this cross-sectional study. Dietary factors were measured via a food frequency questionnaire and three non-consecutive 24 h recalls. Dietary energy density (foods and caloric beverages included) and macronutrient intakes were subsequently estimated using EvalFINUT® software, food group consumption was estimated from the food frequency questionnaire, and different dietary patterns and quality indices were determined according to the reference methods. BAT volume, BAT 18F-FDG uptake, and skeletal muscle 18F-FDG uptake were assessed by static 18F-FDG positron-emission tomography and computed tomography (PET-CT) scans after a 2 h personalized exposure to cold. RESULTS: A direct association was detected between dietary energy density and BAT Standardized Uptake Value (SUV)mean (ß = 0.215; R2 = 0.044; P = 0.022), and between ethanol consumption and BAT volume (ß = 0.215; R2 = 0.044; P = 0.022). The a priori Mediterranean dietary pattern was inversely associated with BAT SUVmean and SUVpeak (ß = -0.273; R2 = 0.075; P = 0.003 and ß = -0.255; R2 = 0.066; P = 0.005 respectively). In addition, the diet quality index for a Mediterranean diet and a pro-inflammatory dietary pattern (as determined via the dietary inflammatory index) were directly associated with BAT SUVmean and SUVpeak (SUVmean: ß = 0.238; R2 = 0.053; P = 0.013 and ß = 0.256; R2 = 0.052; P = 0.012 respectively; SUVpeak: ß = 0.278; R2 = 0.073; P = 0.003 and ß = 0.248; R2 = 0.049; P = 0.016 respectively). After controlling for multiplicity and possible confounders (sex, the evaluation wave and BMI), all the detected associations persisted. CONCLUSION: Dietary factors are slightly associated with BAT volume and/or 18F-FDG uptake after a personalized cold exposure in young adults. Our results provide an overall picture of the potential relationships between dietary factors and BAT-related variables in humans.

Magnetic Resonance Imaging Techniques for Brown Adipose Tissue Detection.

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) methods can non-invasively assess brown adipose tissue (BAT) structure and function. Recently, MRI and MRS have been proposed as a means to differentiate BAT from white adipose tissue (WAT) and to extract morphological and functional information on BAT inaccessible by other means. Specifically, proton MR (1H) techniques, such as proton density fat fraction mapping, diffusion imaging, and intermolecular multiple quantum coherence imaging, have been employed to access BAT microstructure; MR thermometry, relaxometry, and MRI and MRS with 31P, 2H, 13C, and 129Xe have shown to provide complementary information on BAT function. The purpose of the present review is to provide a comprehensive overview of MR imaging and spectroscopy techniques used to detect BAT in rodents and in humans. The present work discusses common challenges of current methods and provides an outlook on possible future directions of using MRI and MRS in BAT studies.

Functional characterization of human brown adipose tissue metabolism.

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

Morphology of the Vasculature and Blood Supply of the Brown Adipose Tissue Examined in an Animal Model by Micro-CT.

We performed micro-CT imaging of the vascular blood supply in the interscapular area of the brown adipose tissue in three mice with the use of intravascular contrast agent Aurovist™. Resulting 3D data rendering was then adapted into 2D resolution with visualization using false color system and grayscale images. These were then studied for the automatic quantification of the blood vessel density within this area. We found the highest most occurring density within arterioles or venules representing smaller blood vessels whereas with the increase of the vessel diameters a lower percentage rate of their presence was observed in the sample. Our study shows that micro-CT scanning in combination with Aurovist™ contrast is suitable for anatomical studies of interscapular area of brown adipose tissue blood vessel supply.

Sex differences on adipose tissue remodeling: from molecular mechanisms to therapeutic interventions.

Sexual dimorphism greatly influences adipose tissue remodeling, which is characterized by changes in the activity, number, and/or size of adipocytes in response to distinct stimuli, including lifestyle and anti-obesity drugs. This sex dependence seems to be due to the anatomical and endocrine disparities between men and women. At the molecular level, sex hormones are believed to mediate such differences and involve estrogen and androgen receptor-induced gene expression. The signaling pathways that regulate adipose tissue metabolism and function include peroxisome proliferator-activated receptor gamma, uncoupling protein 1 (UCP1), 5' adenosine monophosphate-activated protein kinase (AMPK), and mitochondrial oxidative phosphorylation (OXPHOS), among other molecular players. Sex hormone-related pathways also interplay with adrenergic signaling, probably the most well-characterized molecular mechanism implicated in the remodeling of white adipose tissue. This review overviews and integrates the signaling pathways behind sexual dimorphism in adipose tissue remodeling, hoping to increase the knowledge on the pathogenesis of diseases, such as obesity and related comorbidities, and consequently, to drive future studies to investigate the regulation of this tissue homeostasis, either in men or women.

Electroacupuncture Regulates Inguinal White Adipose Tissue Browning by Promoting Sirtuin-1-Dependent PPARγ Deacetylation and Mitochondrial Biogenesis.

Background: Previous studies had suggested that electroacupuncture (EA) can promote white adipose tissue (WAT) browning to counter obesity. But the mechanism was still not very clear. Aim: In this study, we aim to study the effect of EA on promoting inguinal WAT (iWAT) browning and its possible mechanism. Method: Three-week-old rats were randomly divided into a normal diet (ND) group and a high-fat diet (HFD) group. After 10 weeks, the HFD rats were grouped into HFD + EA group and HFD control group. Rats in the EA group were electro-acupunctured for 4 weeks on Tianshu (ST25) acupoint under gas anesthesia with isoflurane, while the rats in HFD group were under gas anesthesia only. Body weight and cumulative food intake were monitored, and H&E staining was performed to assess adipocyte area. The effect of EA on WAT was assessed by qPCR, immunoblotting, immunoprecipitation and Co-immunoprecipitation. Mitochondria were isolated from IWAT to observe the expression of mitochondrial transcription factor A (TFAM). Results: The body weight, WAT/body weight ratio and cumulative food consumption obviously decreased (P < 0.05) in the EA group. The expressions of brown adipose tissue (BAT) markers were increased in the iWAT of EA rats. Nevertheless, the mRNA expressions of WAT genes were suppressed by 4-week EA treatment. Moreover, EA increased the protein expressions of SIRT-1, PPARγ, PGC-1α, UCP1 and PRDM16 which trigger the molecular conversion of iWAT browning. The decrease of PPARγ acetylation was also found in EA group, indicating EA could advance WAT-browning through SIRT-1 dependent PPARγ deacetylation pathway. Besides, we found that EA could activate AMPK to further regulate PGC-1α-TFAM-UCP1 pathway to induce mitochondrial biogenesis. Conclusion: In conclusion, EA can remodel WAT to BAT through inducing SIRT-1 dependent PPARγ deacetylation, and regulating PGC-1α-TFAM-UCP1 pathway to induce mitochondrial biogenesis. This may be one of the mechanisms by which EA affects weight loss.

Contribution of brown adipose tissue to human energy metabolism.

The present "obesogenic' environment has favored excessive energy intake resulting in the current obesity epidemic and its associated diseases. The epidemic has incentivized scientists to develop novel behavioral and pharmacological strategies that enhance energy expenditure to compensate for excessive energy intake. Although physical activity is effective to increase total energy expenditure, it is insufficient to induce negative energy balance and weight loss. With the discovery of brown adipose tissue (BAT) in adult humans, BAT activation soon emerged as a potential strategy for elevating energy expenditure. BAT is the only tissue that expresses uncoupling protein 1, conferring on this tissue high thermogenic capacity due to a low efficiency for mitochondrial ATP generation. Potential manipulation of BAT mass and activity has fueled the interest in altering whole-body energy balance through increased energy expenditure. Remarkable advances have been made in quantifying the amount and activity of BAT in humans. Many studies have concluded that the amount of active BAT appears insufficient to induce meaningful increases in energy expenditure. Thus, the majority of studies report that BAT activation does not influence body weight and metabolic control in humans. Strategies to increase BAT mass and/or to potentiate BAT activity seem necessary.

Applicability of Supraclavicular Oxygenated and Total Hemoglobin Evaluated by Near-Infrared Time-Resolved Spectroscopy as Indicators of Brown Adipose Tissue Density in Humans.

Brown adipose tissue (BAT) may potentially be used in strategies for preventing lifestyle-related diseases. We examine evidence that near-infrared time-resolved spectroscopy (NIRTRS) is capable of estimating human BAT density (BAT-d). The parameters examined in this study are total hemoglobin [total-Hb]sup, oxygenated Hb [oxy-Hb]sup, deoxygenated Hb [deoxy-Hb]sup, Hb O2 saturation (StO2sup), and the reduced scattering coefficient in the supraclavicular region (µs'sup), where BAT deposits can be located; corresponding parameters in the control deltoid region are obtained as controls. Among the NIRTRS parameters, [total-Hb]sup and [oxy-Hb]sup show region-specific increases in winter, compared to summer. Further, [total-Hb]sup and [oxy-Hb]sup are correlated with cold-induced thermogenesis in the supraclavicular region. We conclude that NIRTRS-determined [total-Hb]sup and [oxy-Hb]sup are useful parameters for evaluating BAT-d in a simple, rapid, non-invasive manner.

MRI characteristics of supraclavicular brown adipose tissue in relation to cold-induced thermogenesis in healthy human adults.

BACKGROUND: Brown adipose tissue (BAT) has been proposed as a target to treat obesity and metabolic disease. Currently, 18 F-Fluordeoxyglucose positron emission tomography (FDG-PET) is the standard for BAT-imaging. MRI might be a promising alternative, as it is not associated with ionizing radiation, offers a high resolution, and allows to discriminate different types of soft tissue. PURPOSE: We sought to evaluate whether supraclavicular BAT (scBAT) volume, fat-fraction (FF), and relaxation rate (R2*) determined by MRI can predict its metabolic activity, which was assessed by measurement of cold-induced thermogenesis (CIT). STUDY TYPE: Prospective cohort study. SUBJECTS: Twenty healthy volunteers (9 female, 11 male), aged 18-47 years, with a body mass index (BMI) of 18-30 kg/m2 . FIELD STRENGTH/SEQUENCE: Multiecho gradient MRI for water-fat separation was used on a 3T device to measure the FF and T2 * of BAT. ASSESSMENT: Prior to imaging, CIT was determined by measuring the difference in energy expenditure (EE) during warm conditions and after cold exposure. Volume, FF, and R2* of scBAT was assessed and compared with CIT. In 11 participants, two MRI sessions with and without cold exposure were performed and the dynamic changes in FF and R2* assessed. STATISTICAL TESTS: Linear regression was used to evaluate the relation of MRI measurements and CIT. P-values below 0.05 were considered significant; data are given as mean ± SD. RESULTS: R2* correlated positively with CIT (r = 0.64, R2 = 0.41 P = 0.0041). Volume and FF did not correlate significantly with CIT. After mild cold exposure EE increased significantly (P = 0.0002), with a mean CIT of 147 kcal/day. The mean volume of scBAT was 72.4 ± 38.4 ml, mean FF was 74.3 ± 5.8%, and the mean R2* (1/T2 *) was 33.5 ± 12.7 s-1 . DATA CONCLUSION: R2* of human scBAT can be used to estimate CIT. FF of scBAT was not associated with CIT. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1160-1168.

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

In endothermic animals, brown adipose tissue (BAT) is activated to produce heat for defending body temperature in response to cold. BAT's ability to expend energy has made it a potential target for novel therapies to ameliorate obesity and associated metabolic disorders in humans. Though this tissue has been well studied in small animals, BAT's thermogenic capacity in humans remains largely unknown due to the difficulties of measuring its volume, activity, and distribution. Identifying and quantifying active human BAT is commonly performed using 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography and computed tomography (PET/CT) scans following cold-exposure or pharmacological activation. Here we describe a detailed image-analysis approach to quantify total-body human BAT from 18F-FDG PET/CT scans using an open-source software. We demonstrate the drawing of user-specified regions of interest to identify metabolically active adipose tissue while avoiding common non-BAT tissues, to measure BAT volume and activity, and to further characterize its anatomical distribution. Although this rigorous approach is time-consuming, we believe it will ultimately provide a foundation to develop future automated BAT quantification algorithms.

Association of Objectively Measured Physical Activity With Brown Adipose Tissue Volume and Activity in Young Adults.

Purpose: Human brown adipose tissue (BAT) has gained considerable attention as a potential therapeutic target for obesity and type 2 diabetes; however, whether physical activity (PA) might be an efficient stimulus to activate and recruit BAT remains to be ascertained. We aimed to examine whether objectively measured PA levels were associated with BAT volume and activity in young sedentary adults. We additionally examined the association of PA levels with the skeletal muscles activity. Methods: A total of 130 young healthy and sedentary adults (67% women; age, 21.9 ± 2.1 years old; body mass index, 25 ± 4.8 kg/m2) participated in this cross-sectional study. PA was objectively measured with a wrist-worn accelerometer for 7 consecutive days. Age-specific cut points were applied to classify wrist accelerations into sedentary time and different PA intensities (i.e., light, moderate, vigorous, moderate-vigorous). The participants underwent 2 hours of a personalized cold exposure to determine the cold-induced BAT volume and activity and the skeletal muscles activity by means of an 18F-fluorodeoxyglucose positron emission tomography combined with a CT scan. Results: Objectively measured PA intensity levels were neither associated with BAT volume and activity nor with the skeletal muscles activity (all P > 0.05). The results remained after adjusting for sex, waking time, and environmental temperature. Conclusions: Although PA plays an important role in the prevention of obesity and related comorbidities, it seems that other physiological mechanisms rather than brown adipocyte activation or recruitment might moderate its beneficial metabolic effects in young sedentary adults.

Duration of a "Brown-Like" Phenotype of White Adipose Tissue Induced by the ß3 Agonist CL-316,243.

"Browning" i. e. the transformation of white adipose tissue into brown-like adipose tissue could induce efficient burning of excess fat reserves via induction of non-shivering thermogenesis. For example, activation of ß3 adrenergic receptors has been show to induce such changes, however, it is still not clear, how long after termination of such a treatment, beneficial effects might be maintained. To address this question, we treated rats s.c. for 2 weeks with the ß3 agonist CL-316,243 at 1 mg/kg and assessed interscapular brown fat and inguinal white fat pads weight, UCP-1 (a marker for the brown-like fat phenotype) using immunohistochemistry and H&E staining, at different intervals after treatment termination.One 1 day after the treatment cessation there was a decrease of inguinal white fat pad weight and increase of interscapular fat pad. This change vanished at 7 days for inguinal pad and at 14 days for interscapular pad. Histological analysis of interscapular pads showed increased UCP-1 staining and brown-like morphology in H&E staining slices at 1 day, but not other time points. In case of inguinal pad there were brown-like features in H&E slices at 1 day and less after 7 days, but absent at 14 days. UCP-1 staining was only detected 1 day after the treatment.In conclusion, the present results indicate that browning-like changes of white fat may be short lasting after treatment termination and could require maintenance treatment of inductor to achieve desired therapeutic effect. This might be a serious shortcoming of potential therapeutic use.

Near-Infrared Spatially Resolved Spectroscopy as an Indirect Technique to Assess Brown Adipose Tissue in Young Women.

PURPOSE: Near-infrared spectroscopy (NIRS) has recently been proposed as an indirect technique to assess brown adipose tissue (BAT) in young men. NIRS arises as a novel technique to avoid the limitations of the "gold-standard" 2-deoxy-2-[18F]fluoro-D-glucose ([18F]DG) positron emission tomography combined with X-ray computed tomography (PET/CT). The aim of this study was to examine the association between near-infrared spatially resolved spectroscopy (NIRSRS) parameters and BAT volume and activity estimated by [18F]DG-PET/CT in 18 young healthy women. PROCEDURES: NIRSRS parameters [tissue saturation index and concentrations of total haemoglobin, oxy-haemoglobin, and deoxy-haemoglobin] were continuously measured in the supraclavicular and forearm regions, in both warm and cold (2 h of personalised cold exposure) conditions. Then, the NIRSRS data were analysed as an average of 5 min in 4 different periods: (i) warm period as the baseline record, (ii) cold period I, (iii) cold period II, and (iv) cold period III. The data were then correlated with BAT volume and activity (SUVmean and SUVpeak) estimated by [18F]DG-PET/CT. RESULTS: There was no association between the NIRSRS parameters in the supraclavicular region in warm conditions (no previous cold exposure) and BAT volume and activity (P > 0.05). Similarly, the cold-induced changes of the NIRSRS parameters in the supraclavicular region were not associated with BAT volume and activity (P > 0.05). CONCLUSIONS: NIRSRS does not seem to be a valid technique to indirectly assess BAT in young healthy women. Further research is needed to validate this technique against other methods such as PET/CT using different radiotracers or magnetic resonance imaging.

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

F18-fluorodeoxyglucose (FDG)-positron emission tomography (PET) along with computed tomography (CT) is a standard method for assessing brown adipose tissue (BAT) activity. We tested the usefulness of near-infrared time-resolved spectroscopy (NIRTRS) as a simple and noninvasive method for evaluating BAT density (BAT-d) by examining the effects of some factors known to influence BAT activity. The total hemoglobin concentration as a parameter of BAT-d was evaluated using NIRTRS in the supraclavicular region in 413 Japanese individuals. The associations were analyzed between BAT-d and sex, age, the percentages of body fat (%BF), visceral fat (VF), and the seasonal ambient temperature (AmT) fluctuations. Age was associated with decreased BAT-d (P < 0.05). There was no sex difference in the BAT-d, except for those in their twenties. Multivariate analyses revealed that %BF and VF were correlated with BAT-d, and the lower AmT (around 4°C or 5°C) for 4 and 6 weeks prior to the measurement day was associated with an increase in the BAT-d. Our NIRTRS results were analogous to those reported with FDG18-PET / CT, indicating the usefulness of NIRTRS. BAT-d might increase during the 4 and 6 weeks after the AmT decreases to lower than 4°C or 5°C.

Recent advances in the detection of brown adipose tissue in adult humans: a review.

The activation of brown adipose tissue (BAT) is associated with reductions in circulating lipids and glucose in rodents and contributes to energy expenditure in humans indicating the potential therapeutic importance of targetting this tissue for the treatment of a variety of metabolic disorders. In order to evaluate the therapeutic potential of human BAT, a variety of methodologies for assessing the volume and metabolic activity of BAT are utilized. Cold exposure is often utilized to increase BAT activity but inconsistencies in the characteristics of the exposure protocols make it challenging to compare findings. The metabolic activity of BAT in response to cold exposure has most commonly been measured by static positron emission tomography of 18F-fluorodeoxyglucose in combination with computed tomography (18F-FDG PET-CT) imaging, but recent studies suggest that under some conditions this may not always reflect BAT thermogenic activity. Therefore, recent studies have used alternative positron emission tomography and computed tomography (PET-CT) imaging strategies and radiotracers that may offer important insights. In addition to PET-CT, there are numerous emerging techniques that may have utility for assessing BAT metabolic activity including magnetic resonance imaging (MRI), skin temperature measurements, near-infrared spectroscopy (NIRS) and contrast ultrasound (CU). In this review, we discuss and critically evaluate the various methodologies used to measure BAT metabolic activity in humans and provide a contemporary assessment of protocols which may be useful in interpreting research findings and guiding the development of future studies.

An Adipose Tissue Atlas: An Image-Guided Identification of Human-like BAT and Beige Depots in Rodents.

[18F]Fluorodeoxyglucose-PET/CT (18F-FDG-PET/CT) imaging has been invaluable for visualizing metabolically active adipose tissues in humans with potential anti-diabetic and anti-obesity effects. To explore whether mice display human-like fat depots in anatomically comparable regions, we mapped fat depots using glucose or fatty acid imaging tracers, such as 18F-FDG through PET/CT or [123/125I]-ß-methyl-p-iodophenyl-pentadecanoic acid with SPECT/CT imaging, to analogous depots in mice. Using this type of image analysis with both probes, we define a large number of additional areas of high metabolic activity corresponding to novel fat pads. Histological and gene expression analyses validate these regions as bona fide fat pads. Our findings indicate that fat depots of rodents show a high degree of topological similarity to those of humans. Studies involving both glucose and lipid tracers indicate differential preferences for these substrates in different depots and also suggest that fatty acid-based visualized approaches may reveal additional brown adipose tissue and beige depots in humans.