PurposeBrown adipose tissue (BAT) is considered a potential target for combatting obesity, as it produces heat instead of ATP in cellular respiration due to uncoupling protein-1 (UCP-1) in mitochondria. However, BAT-specific thermogenic capacity, in comparison to whole-body thermogenesis during cold stimulus, is still controversial. In our present study, we aimed to determine human BAT oxygen consumption with [15O]O2 positron emission tomography (PET) imaging. Further, we explored whether BAT-specific energy expenditure (EE) is associated with BAT blood flow, non-esterified fatty acid (NEFA) uptake, and whole-body EE.MethodsSeven healthy study subjects were studied at two different scanning sessions, 1) at room temperature (RT) and 2) with acute cold exposure. Radiotracers [15O]O2, [15O]H2O, and [18F]FTHA were given for the measurements of BAT oxygen consumption, blood flow, and NEFA uptake, respectively, with PET-CT. Indirect calorimetry was performed to assess differences in whole-body EE between RT and cold.ResultsBAT-specific EE and oxygen consumption was higher during cold stimulus (approx. 50 %); similarly, whole-body EE was higher during cold stimulus (range 2–47 %). However, there was no association in BAT-specific EE and whole-body EE. BAT-specific EE was found to be a minor contributor in cold induced whole-body thermogenesis (almost 1 % of total whole-body elevation in EE). Certain deep muscles in the cervico-thoracic region made a major contribution to this cold-induced thermogenesis (CIT) without any visual signs or individual perception of shivering. Moreover, BAT-specific EE associated with BAT blood flow and NEFA uptake both at RT and during cold stimulus.ConclusionOur study suggests that BAT is a minor and deep muscles are a major contributor to CIT. In BAT, both in RT and during cold, cellular respiration is linked with circulatory NEFA uptake.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-016-3364-y) contains supplementary material, which is available to authorized users.
Correspondence mk@tum.de In BriefSecretin, a gut hormone secreted while eating a meal, stimulates brown fat thermogenesis and induction of satiation in mice and humans.
Human studies suggest that a meal elevates glucose uptake in brown adipose tissue (BAT). However, in postprandial state the thermogenic activity and the metabolism of non-esterified fatty acids (NEFAs) in BAT remain unclear. Using indirect calorimetry combined with positron emission tomography and computed tomography (PET/CT), we showed that whole-body and BAT thermogenesis (oxygen consumption) increases after the ingestion of a mixed carbohydrate-rich meal, to the same extent as in cold stress. Postprandial NEFA uptake into BAT is minimal, possibly due to elevated plasma insulin inhibiting lipolysis. However, the variation in postprandial NEFA uptake is linked to BAT thermogenesis. We identified several genes participating in lipid metabolism to be expressed at higher levels in BAT compared with white fat in postprandial state, and to be positively correlated with BAT UCP1 expression. These findings suggest that substrates preferred by BAT in postprandial state are glucose or LPL-released NEFAs due to insulin stimulation.
BAT radiodensity can be used as a marker of underlying tissue morphology. Active BAT can be identified using CT, exploiting tissue composition information. Moreover, BAT radiodensity provides an insight into whole-body systemic metabolic health.
Aims Little is known about the effects of exercise training on brown adipose tissue (BAT) metabolism in humans. We tested the hypothesis that high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) improve BAT insulin sensitivity. Materials and methods Healthy middle-aged men (n = 18, age 47 years [95% confidence interval {CI} 49, 43}, body mass index 25.3 kg/m2 [95% CI 24.1, 26.3], peak oxygen uptake (VO2peak) 34.8 mL/kg/min [95% CI 32.1, 37.4]) were recruited and randomized into six HIIT or MICT sessions within 2 weeks. Insulin-stimulated glucose uptake was measured using 2-[18F]fluoro-2-deoxy-D-glucose positron-emission tomography in BAT, skeletal muscle and abdominal and femoral subcutaneous and visceral white adipose tissue (WAT) depots before and after the training interventions. Results Training improved VO2peak (P=0.0005), insulin-stimulated glucose uptake into quadriceps femoris muscle (P=0.0009) and femoral subcutaneous white adipose tissue (P=0.02), but not into BAT, with no difference between the training modes. Using pre-intervention BAT glucose uptake, we next stratified subjects into high BAT (>2.9μmol/100g/min; n=6) or low BAT (<2.9 μmol/100g/min; n=12) groups. Interestingly, training decreased insulin-stimulated BAT glucose uptake in the high BAT group (4.0 [2.8, 5.5] vs. 2.5 [1.7, 3.6]) (training*BAT, P=0.02), whereas there was no effect of training in the low BAT group (1.5 [1.2, 1.9] vs. 1.6 [1.2, 2.0] μmol·100g·min−1). High BAT subjects had lower levels of inflammatory markers compared to low BAT subjects. Conclusions Subjects with functionally active BAT have an improved metabolic profile compared to subjects with low BAT activity. Short-term exercise training decreases insulin-stimulated BAT glucose uptake in subjects with active BAT, suggesting that training does not work as a potent stimulus for BAT activation.
A decrease in triglyceride content, coupled with the increased proportion of brown adipose tissue in the supraclavicular fat depot, may play a role in the improvement of whole-body insulin sensitivity observed in morbidly obese women after surgery-induced weight loss.
Activating brown adipose tissue (BAT) could provide a potential approach for the treatment of obesity and metabolic disease in humans. Obesity is associated with upregulation of the endocannabinoid system, and blocking the cannabinoid type 1 receptor (CB1R) has been shown to cause weight loss and to decrease cardiometabolic risk factors. These effects may be mediated partly via increased BAT metabolism, since there is evidence that CB1R antagonism activates BAT in rodents. To investigate the significance of CB1R in BAT function, we quantified the density of CB1R in human and rodent BAT using the positron emission tomography radioligand [F]FMPEP- and measured BAT activation in parallel with the glucose analog [F]fluorodeoxyglucose. Activation by cold exposure markedly increased CB1R density and glucose uptake in the BAT of lean men. Similarly, β3-receptor agonism increased CB1R density in the BAT of rats. In contrast, overweight men with reduced BAT activity exhibited decreased CB1R in BAT, reflecting impaired endocannabinoid regulation. Image-guided biopsies confirmed CB1R mRNA expression in human BAT. Furthermore, CB1R blockade increased glucose uptake and lipolysis of brown adipocytes. Our results highlight that CB1Rs are significant for human BAT activity, and the CB1Rs provide a novel therapeutic target for BAT activation in humans.
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