whole-body-regional-quantification-active-human-brown-adipose-tissue

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

In endothermic animals, brown adipose tissue (BAT) is activated to produce heat for defending body temperature in response to cold. BAT&#39;s ability to ...

National Institutes of Health

Abdominal visceral fat, typically measured by computer tomography (CT) or magnetic resonance imaging (MRI), has been shown to correlate with cardiometabolic risks. The purpose of this study was to examine whether a newly developed and validated visceral fat measurement from dual-energy X-ray absorptiometry (DXA) provides added predictive value to the cross-sectional differences of cardiometabolic parameters beyond the traditional anthropometric and DXA adiposity parameters.

Does Visceral Fat Estimated by Dual-Energy X-ray Absorptiometry Independently Predict Cardiometabolic Risks in Adults?

Human brown adipose tissue (BAT) can be activated to increase glucose uptake and energy expenditure, making it a potential target for treating obesity and metabolic disease. Data on the functional and anatomic characteristics of BAT are limited, however. In 20 healthy young men [12 lean, mean body mass index (BMI) 23.2 ± 1.9 kg/m; 8 obese, BMI 34.8 ± 3.3 kg/m] after 5 h of tolerable cold exposure, we measured BAT volume and activity by F-labeled fluorodeoxyglucose positron emission tomography/computerized tomography (PET/CT). Obese men had less activated BAT than lean men (mean, 130 vs. 334 mL) but more fat in BAT-containing depots (mean, 1,646 vs. 855 mL) with a wide range (0.1-71%) in the ratio of activated BAT to inactive fat between individuals. Six anatomic regions had activated BAT-cervical, supraclavicular, axillary, mediastinal, paraspinal, and abdominal-with 67 ± 20% of all activated BAT concentrated in a continuous fascial layer comprising the first three depots in the upper torso. These nonsubcutaneous fat depots amounted to 1.5% of total body mass (4.3% of total fat mass), and up to 90% of each depot could be activated BAT. The amount and activity of BAT was significantly influenced by region of interest selection methods, PET threshold criteria, and PET resolutions. The present study suggests that active BAT can be found in specific adipose depots in adult humans, but less than one-half of the fat in these depots is stimulated by acute cold exposure, demonstrating a previously underappreciated thermogenic potential.

Mapping of human brown adipose tissue in lean and obese young men.

In Iceland, there is a large variation in daylight between summer and winter. The aim of the study was to identify how this large variation influences physical activity (PA) and sedentary behavior (SB). Free living PA was measured by a waist-worn accelerometer for one week during waking hours in 138 community-dwelling older adults (61.1% women, 80.3 ± 4.9 years) during summer and winter months. In general, SB occupied about 75% of the registered wear-time and was highly correlated with age (β = 0.36). Although the differences were small, more time was spent during the summer in all PA categories, except for the moderate-to-vigorous PA (MVPA), and SB was reduced. More lifestyle PA (LSPA) was accumulated in ≥5-min bouts during summer than winter, especially among highly active participants. This information could be important for policy makers and health professionals working with older adults. Accounting for seasonal difference is necessary in analyzing SB and PA data.

Comparison of Summer and Winter Objectively Measured Physical Activity and Sedentary Behavior in Older Adults: Age, Gene/Environment Susceptibility Reykjavik Study.

The aim of this study was to explore how physical activity (PA) and energy intake (EI) changes were related to weight loss and regain following "The Biggest Loser" competition.

Increased Physical Activity Associated with Less Weight Regain Six Years After "The Biggest Loser" Competition.

To adapt and refine a previously-developed youth-specific algorithm to identify bedrest for use in adults. The algorithm is based on using an automated decision tree (DT) analysis of accelerometry data.

Identifying bedrest using 24-h waist or wrist accelerometry in adults.

To date, human studies show that brown adipose tissue (BAT) contributes a small yet highly variable amount to overall energy expenditure. No studies have shown a decrease in body weight with cold-induced BAT activation, and existing pharmacological studies suggest that BAT activation via the sympathetic nervous system may result in increased heart rate and systolic blood pressure. Furthermore, even though the amount and/or activity of BAT have been shown to vary with seasons, such variation does not seem to be translated into weight changes. Collectively, these findings do not support the use of BAT activation for weight loss in humans; however, the potential role of BAT in counteracting the metabolic adaptation observed with weight loss is suggested. Although the role of BAT in weight control is currently unsubstantiated, BAT may play a role in improving insulin sensitivity in humans.

Is activation of human brown adipose tissue a viable target for weight management?

Accurate estimation of energy expenditure (EE) from accelerometer outputs remains a challenge in older adults. The aim of this study was to validate different ActiGraph (AG) equations for predicting EE in older adults. Forty older adults (age = 77.4 ± 8.1 yrs) completed a set of household/gardening activities in their residence, while wearing an AG at the hip (GT3X+) and a portable calorimeter (MetaMax 3B - criterion). Predicted EEs from AG were calculated using five equations (Freedson, refined Crouter, Sasaki and Santos-Lozano (vertical-axis, vectormagnitude)). Accuracy of equations was assessed using root-mean-square error (RMSE) and mean bias. The Sasaki equation showed the lowest RMSE for all activities (0.47 METs) and across physical activity intensities (PAIs) (range 0.18-0.48 METs). The Freedson and Santos-Lozano equations tended to overestimate EE for sedentary activities (range: 0.48 to 0.97 METs), while EEs for moderate-to-vigorous activities (MVPA) were underestimated (range: -1.02 to -0.64 METs). The refined Crouter and Sasaki equations showed no systematic bias, but they respectively overestimated and underestimated EE across PAIs. In conclusion, none of the equations was completely accurate for predicting EE across the range of PAIs. However, the refined Crouter and Sasaki equations showed better overall accuracy and precision when compared with the other methods.

Comparing ActiGraph equations for estimating energy expenditure in older adults.

β3-adrenergic receptor (AR) agonists are approved to treat only overactive bladder. However, rodent studies suggest that these drugs could have other beneficial effects on human metabolism. We performed tissue receptor profiling and showed that the human β3-AR mRNA is also highly expressed in gallbladder and brown adipose tissue (BAT). We next studied the clinical implications of this distribution in 12 healthy men given one-time randomized doses of placebo, the approved dose of 50 mg, and 200 mg of the β3-AR agonist mirabegron. There was a more-than-dose-proportional increase in BAT metabolic activity as measured by [F]-2-fluoro-D-2-deoxy-d-glucose positron emission tomography/computed tomography (medians 0.0 vs. 18.2 vs. 305.6 mL ⋅ mean standardized uptake value [SUV] ⋅ g/mL). Only the 200-mg dose elevated both nonesterified fatty acids (68%) and resting energy expenditure (5.8%). Previously undescribed increases in gallbladder size (35%) and reductions in conjugated bile acids were also discovered. Therefore, besides urinary bladder relaxation, the human β3-AR contributes to white adipose tissue lipolysis, BAT thermogenesis, gallbladder relaxation, and bile acid metabolism. This physiology should be considered in the development of more selective β3-AR agonists to treat obesity-related complications.

Regulation of Human Adipose Tissue Activation, Gallbladder Size, and Bile Acid Metabolism by a β3-Adrenergic Receptor Agonist.

Sedentary children have greater risk of developing abnormalities in glucose homeostasis. We investigated whether interrupting sedentary behavior (sitting) with very short periods of walking would improve glucose metabolism without affecting dietary intake in children with overweight or obesity. We hypothesized that interrupting sitting with short bouts of moderate-intensity walking would decrease insulin area under the curve (AUC) during an oral glucose tolerance test (OGTT) compared with uninterrupted sitting.

Effects of Interrupting Sedentary Behavior With Short Bouts of Moderate Physical Activity on Glucose Tolerance in Children With Overweight and Obesity: A Randomized Crossover Trial.

Altered stress response theoretically contributes to the etiology of cardiometabolic disease. Mindfulness may be a protective buffer against the effects of stress on health outcomes by altering how individuals evaluate and respond to stress. We engaged adolescent girls at risk for developing Type 2 diabetes in a cold-pressor test in order to determine the relationship of dispositional mindfulness to cortisol response and subjective stress, including perceived pain and unpleasantness during the stressor, and negative affect following the stressor. We also evaluated mindfulness as a moderator of psychological distress (depressive/anxiety symptoms) and stress response. Participants were 119 girls age 12-17 years with overweight/obesity, family history of diabetes, and mild-to-moderate depressive symptoms. Greater mindfulness was associated with less perceived pain and negative affect, but was unrelated to cortisol response to the stressor. Regardless of mindfulness, greater depressive/anxiety symptoms related to a more blunted cortisol response. Mindfulness might promote better distress tolerance in adolescents at risk for diabetes by altering how youth perceive and relate to acute stress, rather than through altering the physiological stress response. At all levels of mindfulness, depressive/anxiety symptoms relate to greater blunting of cortisol response. Findings contribute to emerging literature on the role of mindfulness in promoting the mental and physical health and well-being of individuals at risk for Type 2 diabetes.

Relationship of Mindfulness to Distress and Cortisol Response in Adolescent Girls At-Risk for Type 2 Diabetes.

PIK3CA-related overgrowth spectrum (PROS) encompasses a range of debilitating conditions defined by asymmetric overgrowth caused by mosaic activating PIK3CA variants. PIK3CA encodes the p110α catalytic subunit of phosphatidylinositol-3-kinase (PI3K), a critical transducer of growth factor signaling. As mTOR mediates the growth-promoting actions of PI3K, we hypothesized that the mTOR inhibitor sirolimus would slow pathological overgrowth.

Safety and efficacy of low-dose sirolimus in the PIK3CA-related overgrowth spectrum.

Self-reported short sleep duration is associated with greater risk for metabolic syndrome (MetS), obesity, and higher energy intake (EI). However, studies of these associations in children using objective methods are sparse.

Associations of sleep patterns with metabolic syndrome indices, body composition, and energy intake in children and adolescents.

Low-grade inflammation is believed to contribute to the metabolic dysregulation of obesity. Colchicine can reduce inflammation by inhibiting microtubule propagation and inflammasome assembly. We evaluated efficacy and safety of colchicine for improving metabolic and inflammatory outcomes in people with obesity and metabolic syndrome (MetS).

Article	Year
Does Visceral Fat Estimated by Dual-Energy X-ray Absorptiometry Independently Predict Cardiometabolic Risks in Adults? Journal of diabetes science and technology\| PubMed ID: 25802470	2015
Mapping of human brown adipose tissue in lean and obese young men. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 28739898	2017
Comparison of Summer and Winter Objectively Measured Physical Activity and Sedentary Behavior in Older Adults: Age, Gene/Environment Susceptibility Reykjavik Study. International journal of environmental research and public health\| PubMed ID: 29065475	2017
Increased Physical Activity Associated with Less Weight Regain Six Years After "The Biggest Loser" Competition. Obesity (Silver Spring, Md.)\| PubMed ID: 29086499	2017
Identifying bedrest using 24-h waist or wrist accelerometry in adults. PloS one\| PubMed ID: 29570740	2018
Is activation of human brown adipose tissue a viable target for weight management? American journal of physiology. Regulatory, integrative and comparative physiology\| PubMed ID: 29741929	2018
Comparing ActiGraph equations for estimating energy expenditure in older adults. Journal of sports sciences\| PubMed ID: 29912666	2018
Regulation of Human Adipose Tissue Activation, Gallbladder Size, and Bile Acid Metabolism by a β3-Adrenergic Receptor Agonist. Diabetes\| PubMed ID: 29980535	2018
Effects of Interrupting Sedentary Behavior With Short Bouts of Moderate Physical Activity on Glucose Tolerance in Children With Overweight and Obesity: A Randomized Crossover Trial. Diabetes care\| PubMed ID: 30082324	2018
Relationship of Mindfulness to Distress and Cortisol Response in Adolescent Girls At-Risk for Type 2 Diabetes. Journal of child and family studies\| PubMed ID: 30100695	2018
Safety and efficacy of low-dose sirolimus in the PIK3CA-related overgrowth spectrum. Genetics in medicine : official journal of the American College of Medical Genetics\| PubMed ID: 30270358	2018
Associations of sleep patterns with metabolic syndrome indices, body composition, and energy intake in children and adolescents. Pediatric obesity\| PubMed ID: 30702801	2019
Effects of Colchicine in Adults with Metabolic Syndrome: A Pilot Randomized Controlled Trial. Diabetes, obesity & metabolism\| PubMed ID: 30869182	2019

Kong Y. Chen

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