Brown adipose tissue activity after a high-calorie meal in humans.

BACKGROUND: Studies in rodents have shown that brown adipose tissue (BAT) is activated on food intake, thereby reducing metabolic efficiency. OBJECTIVE: The current study investigated whether a single high-calorie, carbohydrate-rich meal activates BAT in lean human adults. DESIGN: BAT activity was studied in 11 lean adult men [age: 23.6 +/- 2.1 y; body mass index (BMI; in kg/m2): 22.4 +/- 2.1] after consumption of a high-calorie, carbohydrate-rich meal (1622 +/- 222 kcal; 78% carbohydrate, 12% P, 10% F). BAT activity during 2 h of mild cold exposure served as a positive control experiment. BAT activity was assessed by [18F]fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography. Energy expenditure was measured by indirect calorimetry. RESULTS: Postprandial [18F]FDG uptake was significantly higher in BAT [1.65 +/- 0.99 mean standard uptake value (SUVmean)] than in subcutaneous (0.35 +/- 0.15 SUVmean; P < 0.05) and visceral (0.49 +/- 0.24 SUVmean; P < 0.05) white adipose tissue and liver (0.95 +/- 0.28 SUVmean; P < 0.05). Postprandial BAT activity was lower than cold-induced BAT activity (7.19 +/- 2.09 SUVmean). However, postprandial BAT activity may have been underestimated because of high postprandial [18F]FDG uptake in skeletal muscle compared with cold (1.36 +/- 0.31 compared with 0.59 +/- 0.07 SUVmean, P < 0.05), which reduces [18F]FDG bioavailability for BAT and other tissues. No direct relation was found between BAT and diet-induced thermogenesis (DIT). CONCLUSIONS: Glucose uptake in BAT increases after a meal in humans, which indicates a role for BAT in reducing metabolic efficiency. However, the quantitative contribution of BAT to DIT relative to other tissues, such as skeletal muscle, remains to be investigated. This trial was registered at www.controlled-trials.com as ISRCTN21413505

Temporal and thermal variations in site-specific thermoregulatory sudomotor thresholds: precursor versus discharged sweat production

Temporal and thermal differences between the initiation of precursor, eccrine sweat and its surface discharge were investigated during passive heating. Sudomotor activity was evaluated using electrodermal (precursor) and ventilated sweat capsule measurements (dorsal fingers, dorsal hand, forehead, forearm). Passive heating significantly elevated auditory canal (0.5oC) and mean body temperatures (0.9oC). At each site, the precursor sudomotor thresholds occurred at a lower mean body temperature (P \u3c .05), with an average elevation of 0.35oC (SD 0.04). However, discharged thresholds were delayed until this temperature had risen 0.53oC (SD 0.04), producing significant phase delays across sites (mean: 4.1 min [SD 0.5]; P \u3c .05). It is concluded that precise sudomotor threshold determinations require methods that respond to sweat accumulating within the secretory coil, and not discharged secretions, reinforcing the importance of electrodermal techniques

Frequent Extreme Cold Exposure and Brown Fat and Cold-Induced Thermogenesis: A Study in a Monozygotic Twin

<div><p>Introduction</p><p>Mild cold acclimation is known to increase brown adipose tissue (BAT) activity and cold-induced thermogenesis (CIT) in humans. We here tested the effect of a lifestyle with frequent exposure to extreme cold on BAT and CIT in a Dutch man known as ‘the Iceman’, who has multiple world records in withstanding extreme cold challenges. Furthermore, his monozygotic twin brother who has a ‘normal’ sedentary lifestyle without extreme cold exposures was measured.</p><p>Methods</p><p>The Iceman (subject A) and his brother (subject B) were studied during mild cold (13°C) and thermoneutral conditions (31°C). Measurements included BAT activity and respiratory muscle activity by [¹⁸F]FDG-PET/CT imaging and energy expenditure through indirect calorimetry. In addition, body temperatures, cardiovascular parameters, skin perfusion, and thermal sensation and comfort were measured. Finally, we determined polymorphisms for uncoupling protein-1 and β3-adrenergic receptor.</p><p>Results</p><p>Subjects had comparable BAT activity (A: 1144 SUV_total and B: 1325 SUV_total), within the range previously observed in young adult men. They were genotyped with the polymorphism for uncoupling protein-1 (G/G). CIT was relatively high (A: 40.1% and B: 41.9%), but unlike during our previous cold exposure tests in young adult men, here both subjects practiced a g-Tummo like breathing technique, which involves vigorous respiratory muscle activity. This was confirmed by high [¹⁸F]FDG-uptake in respiratory muscle.</p><p>Conclusion</p><p>No significant differences were found between the two subjects, indicating that a lifestyle with frequent exposures to extreme cold does not seem to affect BAT activity and CIT. In both subjects, BAT was not higher compared to earlier observations, whereas CIT was very high, suggesting that g-Tummo like breathing during cold exposure may cause additional heat production by vigorous isometric respiratory muscle contraction. The results must be interpreted with caution given the low subject number and the fact that both participants practised the g-Tummo like breathing technique.</p></div

Study protocol.

<p>The thermoneutral experiment started in the morning on day one. After one hour a blood sample was taken and subsequently the [¹⁸F]FDG tracer was injected followed by the PET-CT scan one hour later. In the afternoon of day one, the shivering experiment was conducted, which started with a baseline period of 45 minutes during 31°C followed by 90 minutes of mild cold exposure (31°C) to determine the ambient temperature at which shivering occurred. The mild cold experiment on day two consisted of 45 minutes baseline (31°C) followed by 150 minutes of cold exposure. Blood samples were taken at the end of the baseline period and 90 and 150 minutes after the onset of cold exposure. The [¹⁸F]FDG tracer was injected 90 minutes after the onset of cold exposure, followed by the PET-CT scan one hour later.</p

Subject characteristics.

<p>*<i>WI  =  work index, SI  =  sport index, LI  =  leisure time index</i>,</p

Brown adipose tissue and respiratory muscle activity during the thermoneutral and cold exposure experiment. A, D

<p>) PET images during thermoneutral (left) and cold (right) conditions showing [¹⁸F]FDG-uptake e in brown adipose tissue (BAT; red arrows) and respiratory muscles (RM; white arrows). <b>B, E</b>) Transaxial slices of subject A (5 mm thick) of thoracic area (upper) and supraclavicular area (lower) demonstrating BAT activity (red arrows) and RM activity (white arrows). <b>C, F</b>) [¹⁸F]FDG-uptake (SUV_mean) in BAT, white adipose tissue (WAT), skeletal muscle (SM), and respiratory muscles (RM) during thermoneutral and cold conditions.</p

Metabolic, cardiovascular and thermoregulatory parameters during mild-cold experiment.

<p>Metabolic, cardiovascular and thermoregulatory parameters during mild-cold experiment.</p

LysoPC-acyl C16:0 is associated with brown adipose tissue activity in men

INTRODUCTION: Brown adipose tissue (BAT) recently emerged as a potential therapeutic target in the treatment of obesity and associated disorders due to its fat-burning capacity. The current gold standard in assessing BAT activity is [(18)F]FDG PET-CT scan, which has severe limitations including radiation exposure, being expensive, and being labor-intensive. Therefore, indirect markers are needed of human BAT activity and volume. OBJECTIVE: We aimed to identify metabolites in serum that are associated with BAT volume and activity in men. METHODS: We assessed 163 metabolites in fasted serum of a cohort of twenty-two healthy lean men (age 24.1 (21.7–26.6) years, BMI 22.1 (20.5–23.4) kg/m(2)) who subsequently underwent a cold-induced [(18)F]FDG PET-CT scan to assess BAT volume and activity. In addition, we included three replication cohorts consisting of in total thirty-seven healthy lean men that were similar with respect to age and BMI compared to the discovery cohort. RESULTS: After correction for multiple testing, fasting concentrations of lysophosphatidylcholine-acyl (LysoPC-acyl) C16:1, LysoPC-acyl C16:0 and phosphatidylcholine-diacyl C32:1 showed strong positive correlations with BAT volume (β= 116 (85–148) mL, R(2) = 0.81, p = 4.6 × 10(−7) (;) β = 79 (93–119) mL, R(2) = 0.57, p = 5.9 × 10(−4) and β= 91 (40–141) mL, R(2) = 0.52, p = 1.0 × 10(−3), respectively) as well as with BAT activity (β= 0.20 (0.11–0.29) g/mL, R(2) = 0.59, p = 1.9 × 10(−4); β = 0.15 (0.06–0.23) g/mL, R(2) = 0.47, p = 2.0 × 10(−3) and β= 0.13 (0.01–0.25) g/mL, R(2) = 0.28, p = 0.04, respectively). When tested in three independent replication cohorts (total n = 37), the association remained significant between LysoPC-acyl C16:0 and BAT activity in a pooled analysis (β= 0.15 (0.07–0.23) g/mL, R(2) = 0.08, p = 4.2 × 10(−4)). CONCLUSIONS: LysoPC-acyl C16:0 is associated with BAT activity in men. Since BAT is regarded as a promising tool in the battle against obesity and related disorders, the identification of such a noninvasive marker is highly relevant. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-017-1185-z) contains supplementary material, which is available to authorized users