“…Outliers were identify using the Interquartile Range Method. One outlier (white square) was detected and replaced by the mean of this group and a previous study 42 .…”
Pharmacological stimulation of human brown adipose tissue (BAT) has been hindered by either ineffective activation or undesirable off-target secondary effects. Oral administration of the maximal allowable dose of mirabegron (200 mg), a β3-adrenergic receptor (β3-AR) agonist, has been effective in stimulating BAT thermogenesis and whole-body energy expenditure. However, this too has been accompanied by undesirable cardiovascular effects. Combining mirabegron with a cardio-selective β1-AR antagonist could not only suppress these unwanted effects, but potentially increase the sensitivity of the β3-AR and β2-AR in WAT and BAT. Here we report that co-ingesting a high dose of the β1-AR antagonist bisoprolol with mirabegron suppresses the increase in heart rate, systolic blood pressure and myocardial oxygen consumption. However, it also blunted the mirabegron-stimulated increase in BAT lipolysis, thermogenesis and glucose uptake. Whether the attenuation in BAT blood flow induced by the large dose of bisoprolol limited BAT thermogenesis remains to be determined. Clinical Trial Registration ID #:NCT04823442
“…Outliers were identify using the Interquartile Range Method. One outlier (white square) was detected and replaced by the mean of this group and a previous study 42 .…”
Pharmacological stimulation of human brown adipose tissue (BAT) has been hindered by either ineffective activation or undesirable off-target secondary effects. Oral administration of the maximal allowable dose of mirabegron (200 mg), a β3-adrenergic receptor (β3-AR) agonist, has been effective in stimulating BAT thermogenesis and whole-body energy expenditure. However, this too has been accompanied by undesirable cardiovascular effects. Combining mirabegron with a cardio-selective β1-AR antagonist could not only suppress these unwanted effects, but potentially increase the sensitivity of the β3-AR and β2-AR in WAT and BAT. Here we report that co-ingesting a high dose of the β1-AR antagonist bisoprolol with mirabegron suppresses the increase in heart rate, systolic blood pressure and myocardial oxygen consumption. However, it also blunted the mirabegron-stimulated increase in BAT lipolysis, thermogenesis and glucose uptake. Whether the attenuation in BAT blood flow induced by the large dose of bisoprolol limited BAT thermogenesis remains to be determined. Clinical Trial Registration ID #:NCT04823442
“…BAT volumes were not calculated as these are markedly influenced by various factors (e.g., diet, intracellular triglyceride stores, and thresholds for standard uptake value). 18 , 19 Figure 3 The effect of salbutamol vs. salbutamol with propranolol on glucose uptake by brown adipose tissue, skeletal muscle, and subcutaneous white adipose tissue and the association with the change in energy expenditure (A) The glucose uptake by human brown adipose tissue (BAT), skeletal muscle (i.e., average of m. pectoralis, m. trapezius, m. deltoideus, and m. sternocleidomastoideus), and subcutaneous white adipose tissue (scWAT) after salbutamol (n = 10) vs. salbutamol with propranolol (n = 10). A paired Student’s t test, or nonparametric equivalent, was used to compare the two treatment regimes.…”
“…test the effects of high-glucose or -fructose diets on brown adipose tissue (BAT) function in humans. 1 Our ancestors consumed fructose only a few months a year at the time of harvest, amounting to about 20 g per day. However, with modern diets and the use of artificial sweeteners, such as high fructose corn syrup, consumption has more than quadrupled.…”
Section: Main Textmentioning
confidence: 99%
“…test the hypothesis that a high-fructose (HF) diet impairs BAT function, which may be an important contributor to fructose-induced metabolic dysfunction in humans. 1 They further postulate that HF feeding changes the composition of the microbiome, increasing short-chain fatty acid levels, and thereby suppressing oxidative metabolism and blunting intracellular TG depletion during BAT activation. To test this hypothesis, they conducted a randomized crossover study of ten young (ages 20–40 years), non-obese men exposed to 2 weeks of fructose or glucose overfeeding separated by a 4-week isocaloric washout period.…”
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