Using positron-emission tomography (PET), we found that cold-induced glucose uptake was increased by a factor of 15 in paracervical and supraclavicular adipose tissue in five healthy subjects. We obtained biopsy specimens of this tissue from the first three consecutive subjects and documented messenger RNA (mRNA) and protein levels of the brown-adipocyte marker, uncoupling protein 1 (UCP1). Together with morphologic assessment, which showed numerous multilocular, intracellular lipid droplets, and with the results of biochemical analysis, these findings document the presence of substantial amounts of metabolically active brown adipose tissue in healthy adult humans.

We investigated the metabolism of human brown adipose tissue (BAT) in healthy subjects by determining its cold-induced and insulin-stimulated glucose uptake and blood flow (perfusion) using positron emission tomography (PET) combined with computed tomography (CT). Second, we assessed gene expression in human BAT and white adipose tissue (WAT). Glucose uptake was induced 12-fold in BAT by cold, accompanied by doubling of perfusion. We found a positive association between whole-body energy expenditure and BAT perfusion. Insulin enhanced glucose uptake 5-fold in BAT independently of its perfusion, while the effect on WAT was weaker. The gene expression level of insulin-sensitive glucose transporter GLUT4 was also higher in BAT as compared to WAT. In conclusion, BAT appears to be differently activated by insulin and cold; in response to insulin, BAT displays high glucose uptake without increased perfusion, but when activated by cold, it dissipates energy in a perfusion-dependent manner.

Objective: Inactive brown adipose tissue (BAT) may predispose to weight gain. This study was designed to measure metabolism in the BAT of obese humans, and to compare it to that in lean subjects. The impact of weight loss on BAT and the association of detectable BAT with various metabolic characteristics were also assessed. Design and Methods: Using positron emission tomography (PET), cold-and insulin-stimulated glucose uptake and blood flow in the BAT of obese and lean humans were quantified. Further, cold-induced glucose uptake was measured in obese subjects before and after a 5-month conventional weight loss. Results: Mean responses in BAT glucose uptake rate to both cold and insulin stimulation were twice as large in lean as in obese subjects. Blood flow in BAT was also lower in obese subjects under cold conditions. The increase in cold-induced BAT glucose uptake rate after weight loss was not statistically significant. Subjects with cold-activated detectable BAT were leaner and had higher whole-body insulin sensitivity than BAT-negative subjects, irrespective of age and gender. Conclusions: The effects of cold and insulin on BAT activity are severely blunted in obesity, and the presence of detectable BAT may contribute to a metabolically healthy status.

Hyperthyroidism increases GU in BAT independently of BAT perfusion. Hyperthyroid patients are characterized by increased skeletal muscle metabolism and lipid oxidation rates.

The aim of the present study was to determine whether single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) can non-invasively assess triglyceride content in both supraclavicular fat depots and subcutaneous white adipose tissue (WAT) to determine whether these measurements correlate to metabolic variables. A total of 25 healthy volunteers were studied using (18)F-fluorodeoxyglucose positron emission tomography (PET) and (15)O-H2O PET perfusion during cold exposure, and (1)H-MRS at ambient temperature. Image-guided biopsies were collected from nine volunteers. The supraclavicular triglyceride content determined by (1)H-MRS varied between 60 and 91% [mean ± standard deviation (s.d.) 77 ± 10%]. It correlated positively with body mass index, waist circumference, subcutaneous and visceral fat masses and 8-year diabetes risk based on the Framingham risk score and inversely with HDL cholesterol and insulin sensitivity (M-value; euglycaemic-hyperinsulinaemic clamp). Subcutaneous WAT had a significantly higher triglyceride content, 76-95% (mean ± s.d. 87 ± 5%; p = 0.0002). In conclusion, the triglyceride content in supraclavicular fat deposits measured by (1)H-MRS may be an independent marker of whole-body insulin sensitivity, independent of brown adipose tissue metabolic activation.

Objective: Brown adipose tissue (BAT) activity correlates negatively with obesity and insulin resistance, and BAT has been suggested to act as a protective factor against atherogenesis. We aimed to examine subclinical atherosclerosis and risk factor levels in a group of individuals who had 5 years earlier participated in positron-emission tomography studies with measurements of BAT activity. Approach and Results: Study cohort (males/females=5/26, baseline age 41.4±7.9 years; body mass index, 26.8±6.3 kg/m 2 ) underwent positron-emission tomography imaging at baseline with [ 18 F] FDG (glucose uptake) and [ 15 O] H 2 O (perfusion) to measure BAT activity during cold exposure. At 5-year follow-up, ultrasound was performed to measure carotid intima-media thickness, carotid distensibility (a marker of arterial elasticity), and brachial flow-mediated dilation (an estimate of endothelial function). Fasting plasma lipids and hemoglobin A1c were measured from venous samples at baseline and at follow-up. Median values were used as cut points for high cold-induced BAT activity (BAT glucose uptake >2.40 μmoL/100 g per minute and perfusion >8.4 mL/100 g per minute). Baseline cold-induced BAT glucose uptake and perfusion correlated directly with carotid distensibility and inversely with mean bulbus intima-media thickness and maximum intima-media thickness ( P always ≤0.02). Baseline body mass index, plasma triglycerides, and HbA1c correlated negatively with BAT glucose uptake and perfusion in cold ( P always ≤0.048). Correlations between cold-induced BAT activity, cardiovascular risk factors, and atherosclerosis were attenuated with corrections for multiple comparisons. Conclusions: Cold-induced BAT activity at baseline seems to correlate with lower levels of conventional cardiovascular risk factors at baseline and with lower carotid intima-media thickness and higher carotid elasticity at 5-year follow-up.

Brown adipose tissue (BAT) is able to generate heat and dissipate energy in response to cold exposure in mammals. It has recently been acknowledged that adult humans also have functional BAT, whose metabolic activity is reduced in obesity. In healthy humans, the cerebral mechanisms that putatively control BAT function are unclear. By using positron emission tomography (PET), we showed that cold-induced BAT activation is associated with glucose metabolism in the cerebellum, thalamus, and cingulate, temporoparietal, lateral frontal, and occipital cortices in lean participants, whereas no such associations were found under warm control conditions. The cold-induced increase in cerebral glucose metabolism was more robust in lean than obese participants. Cerebral glucose metabolism was not associated with skeletal muscle or white adipose tissue glucose uptake under warm or cold conditions. In conclusion, BAT metabolism was accompanied by the activation of specific cerebral regions, and this shows an uncharacterized role that the brain plays in the regulation of BAT function. In obese participants, the cold-induced response in cerebral activity was attenuated that provides a clue for obesity-induced impairment in BAT metabolism.

Background Sympathetic activity causes changes in electrocardiogram (ECG) during cold exposure and the changes have been studied mostly during hypothermia and less during mild acute nonshivering cold exposure. Cold‐induced sympathetic activity also activates brown adipose tissue (BAT) and increases arterial blood pressure (BP) and plasma catecholamine levels. We examined changes in ECG parameters during acute nonshivering cold exposure and their associations with markers of sympathetic activity during cold exposure: brachial blood pressure (BP), plasma catecholamine levels, and BAT activity measured by positron emission tomography (PET). Methods and results Healthy subjects (M/F = 13/24, aged 20–55 years) were imaged with [15O]H2O (perfusion, N = 37) and [18F]FTHA to measure plasma nonesterified fatty acid uptake (NEFA uptake, N = 37) during 2‐h nonshivering cold exposure. 12‐lead ECG (N = 37), plasma catecholamine levels (N = 17), and brachial BP (N = 31) were measured at rest in room temperature (RT) and re‐measured after a 2‐h nonshivering cold exposure. There were significant differences between RT and cold exposure in P axis (35.6 ± 26.4 vs. 50.8 ± 22.7 degrees, p = 0.005), PR interval (177.7 ± 24.6 ms vs.163.0 ± 28.7 ms, p = 0.001), QRS axis (42.1 ± 31.3 vs. 56.9 ± 24.1, p = 0.003), and QT (411.7 ± 25.5 ms vs. 434.5 ± 39.3 ms, p = 0.001). There was no significant change in HR, QRS duration, QTc, JTc, and T axis during cold exposure. Systolic BP (127.2 ± 15.7 vs. 131.8 ± 17.9 mmHg, p = 0.008), diastolic BP (81.7 ± 12.0 vs. 85.4 ± 13.0 mmHg, p = 0.02), and plasma noradrenaline level increased during cold exposure (1.97 ± 0.61 vs. 5.07 ± 1.32 µmol/L, p = 0.001). Cold‐induced changes in ECG parameters did not correlate with changes in BAT activity, brachial BP, plasma catecholamines, or skin temperature. Conclusions During short‐term nonshivering cold exposure, there were increases in P axis, PR interval, QRS axis, and QT compared to RT in healthy adults. Cold‐induced changes in ECG parameters did not correlate with BAT activity, brachial BP, or plasma catecholamine levels which were used as markers of cold‐induced sympathetic activity.