Ephedrine activates brown adipose tissue in lean but not obese humans

Carey, Andrew L.; Formosa, Melissa F.; Every, Bruce Van; Bertovic, David A.; Eikelis, Nina; Lambert, Gavin W.; Kalff, Victor; Duffy, Stephen J.; Cherk, Martin H; Kingwell, Bronwyn A.

doi:10.1016/j.orcp.2013.12.555

Cited by 24 publications

(41 citation statements)

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“…Overall, while the TZD prescription rate is lower now than in 2007, currently, 10% of all prescriptions for patients with type 2 diabetes in the THIN cohort are prescribed a TZD [37] and pioglitazone retains its position at the frontline of diabetes management [19,37]. Obesity, type 2 diabetes and BAT dysfunction are all linked [24,38,39]. While evidence supporting the association with BAT dysfunction in humans is associative only, the possibility that BAT dysfunction contributes to obesity and metabolic dysregulation cannot be dismissed.…”

Section: Discussionmentioning

confidence: 99%

“…PET/CT imaging PET/CT imaging and analyses were conducted as previously described [7,24], except PET/CT image acquisition and reconstruction was carried out using a GE Discovery 710 PET/CT scanner (GE, Fairfield, CT, USA) and analysis was performed using MIM software v6.6 (MIM Software, Cleveland, OH, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Biochemical analyses Where indicated, plasma was centrifuged and frozen for analyses or whole blood was collected in an appropriate preservative and measured immediately as described [7,24].…”

Section: Methodsmentioning

confidence: 99%

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Pioglitazone reduces cold-induced brown fat glucose uptake despite induction of browning in cultured human adipocytes: a randomised, controlled trial in humans

et al. 2017

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Aims/hypothesis Increasing brown adipose tissue (BAT) activity is a possible therapeutic strategy to increase energy expenditure and glucose and lipid clearance to ameliorate obesity and associated comorbidities. The thiazolidinedione (TZD) class of glucose-lowering drugs increase BAT browning in preclinical experimental models but whether these actions extend to humans in vivo is unknown. The aim of this study was to determine the effect of pioglitazone treatment on adipocyte browning and adaptive thermogenesis in humans. Methods We first examined whether pioglitazone treatment of cultured human primary subacromioclavicular-derived adipocytes induced browning. Then, in a blinded, placebo-controlled, parallel trial, conducted within the Baker Institute clinical research laboratories, 14 lean male participants who were free of cardiometabolic disease were randomised to receive either placebo (lactose; n = 7, age 22 ± 1 years) or pioglitazone (45 mg/day, n = 7, age 21 ± 1 years) for 28 days. Participants were allocated to treatments by Alfred Hospital staff independent from the study via electronic generation of a random number sequence. Researchers conducting trials and analysing data were blind to treatment allocation. The change in cold-stimulated BAT activity, assessed before and after the intervention by [ 18 F]fluorodeoxyglucose uptake via positron emission tomography/computed tomography in upper thoracic and cervical adipose tissue, was the primary outcome measure. Energy expenditure, cardiovascular responses, core temperature, blood metabolites and hormones were measured in response to acute cold exposure along with body composition before and after the intervention. Results Pioglitazone significantly increased in vitro browning and adipogenesis of adipocytes. In the clinical trial, coldElectronic supplementary material The online version of this article (https://doi.org/10.1007/s00125-017-4479-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users. -017-4479-9 induced BAT maximum standardised uptake value was significantly reduced after pioglitazone compared with placebo (−57 ± 6% vs −12 ± 18%, respectively; p < 0.05). BAT total glucose uptake followed a similar but non-significant trend (−50 ± 10% vs −6 ± 24%, respectively; p = 0.097). Pioglitazone increased total and lean body mass compared with placebo (p < 0.05). No other changes between groups were detected. Conclusions/interpretation The disparity in the actions of pioglitazone on BAT between preclinical experimental models and our in vivo human trial highlight the imperative to conduct human proof-of-concept studies as early as possible in BAT research programmes aimed at therapeutic development. Our clinical trial findings suggest that reduced BAT activity may contribute to weight gain associated with pioglitazone and other TZDs.Trial registration ClinicalTrials.gov NCT02236962

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Pioglitazone reduces cold-induced brown fat glucose uptake despite induction of browning in cultured human adipocytes: a randomised, controlled trial in humans

et al. 2017

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“…In order to determine the metabolic activity (i.e. glucose uptake) of BAT, the participants underwent 18 F-fluorodeoxyglucose ( 18 F-FDG) positron-emission tomography (PET)-computed tomography (CT). For the assessment of the sympathetic stimulation of BAT, a 123 I-metaiodobenzylguanidine ( 123 I-MIBG) single-photon emission computed tomography (SPECT)-CT was performed.…”

Section: Methodsmentioning

confidence: 99%

Cold-induced activity of brown adipose tissue in young lean men of South-Asian and European origin

et al. 2013

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Aims/hypothesis South Asians have a disproportionately high risk of developing abdominal obesity, insulin resistance and type 2 diabetes. Brown adipose tissue (BAT) has been identified as a possible target to fight obesity and protect against metabolic disturbance. We explored whether lower BAT activity in South Asians compared with Europids may contribute to the high risk of metabolic disturbance. Methods We studied 20 healthy men (ten Europids/ten South Asians, BMI 19-25 kg/m 2 , age 18-32 years). Following 2 h of cold exposure (16-18°C) after an overnight fast, 18 F-fluorodeoxyglucose ( 18 F-FDG) positronemission tomography-computed tomography (CT) and 123 I-metaiodobenzylguanidine ( 123 I-MIBG) single-photon emission computed tomography-CT were performed to visualise metabolic BAT activity and sympathetic stimulation of BAT. Metabolic BAT activity was defined as maximal standardised uptake value (SUV max ) of 18 F-FDG, and sympathetic stimulation of BAT as semiquantitative uptake value (SQUV) of 123 I-MIBG. We performed hyperinsulinaemic-euglycaemic clamps to assess insulin sensitivity. Spearman's correlations for SUV max of 18 F-FDG and both SQUV of 123 I-MIBG and insulin sensitivity were determined. Results The median (interquartile range) SUV max of 18 F-FDG in South Asians (7.5 [2.2-10.6] g/ml) was not different from the median SUV max obtained in Europids (4.5 [2.2-8.4] g/ml; p=0.59). There was no correlation between BAT activity and insulin sensitivity. Correlations between SQUV of 123 I-MIBG and SUV max of 18 F-FDG were positive, both in the total population (ρ=0.80, p<0.001) and after stratification by ethnicity (Europids, ρ =0.65, p = 0.04; South Asians, ρ=0.83, p=0.01). Conclusions/interpretation This is the first study to prospectively investigate ethnic differences in metabolic BAT activity during cold exposure. We did not find differences in BAT activity between South Asians and Europids. Therefore, it seems unlikely that BAT plays an important role in the development of unfavourable metabolic profiles in South Asians.

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“…The process of beige adipocytes appearing in white AT is referred to as ''AT browning'' and is regulated by a number of factors. For example, norepinephrine (NE) can act via the b 3 -adrenergic receptor to induce AT browning, and this response is impaired in obese humans (3). A higher proportion of beige AT is thought to be protective from weight gain because higher expression of UCP1 increases thermogenesis and wholebody energy expenditure.…”

Section: Role Of At In Obesitymentioning

confidence: 99%

Obesity-Associated Adipose Tissue Inflammation and Transplantation

Wu¹,

Dawson²,

Levings³

2016

American Journal of Transplantation

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Obesity is often associated with the development of adipose tissue (AT) inflammation, resulting in metabolic dysfunction and an increased risk for developing type 2 diabetes. It is also associated with multiple chronic diseases, including cardiovascular, liver, and kidney disease, and thus can contribute to organ failure. Several studies have investigated whether there is a correlation between obesity and outcomes in transplantation, but there is currently very limited information on the specific role of AT inflammation in the rejection process or on the overall function of the transplanted organ. Here, we provide a brief review of the current understanding of the cellular mechanisms that control obesity-associated AT inflammation and summarize knowledge about how obesity affects clinical outcomes following solid organ or hematopoietic stem cell transplantation. We also highlight opportunities for more research to better understand how obesity affects outcomes of transplantation.

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Ephedrine activates brown adipose tissue in lean but not obese humans

Cited by 24 publications

References 0 publications

Pioglitazone reduces cold-induced brown fat glucose uptake despite induction of browning in cultured human adipocytes: a randomised, controlled trial in humans

Pioglitazone reduces cold-induced brown fat glucose uptake despite induction of browning in cultured human adipocytes: a randomised, controlled trial in humans

Cold-induced activity of brown adipose tissue in young lean men of South-Asian and European origin

Obesity-Associated Adipose Tissue Inflammation and Transplantation

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