Dataset Information

The effect of mirabegron on energy expenditure and brown adipose tissue in healthy lean South Asian and Europid men.

ABSTRACT:

Aim

To compare the effects of cold exposure and the ?3-adrenergic receptor agonist mirabegron on plasma lipids, energy expenditure and brown adipose tissue (BAT) activity in South Asians versus Europids.

Materials and methods

Ten lean Dutch South Asian (aged 18-30?years; body mass index [BMI] 18-25 kg/m² ) and 10 age- and BMI-matched Europid men participated in a randomized, double-blinded, cross-over study consisting of three interventions: short-term (~?2?hours) cold exposure, mirabegron (200?mg one dose p.o.) and placebo. Before and after each intervention, we performed lipidomic analysis in serum, assessed resting energy expenditure (REE) and skin temperature, and measured BAT fat fraction by magnetic resonance imaging.

Results

In both ethnicities, cold exposure increased the levels of several serum lipid species, whereas mirabegron only increased free fatty acids. Cold exposure increased lipid oxidation in both ethnicities, while mirabegron increased lipid oxidation in Europids only. Cold exposure and mirabegron enhanced supraclavicular skin temperature in both ethnicities. Cold exposure decreased BAT fat fraction in both ethnicities. After the combination of data from both ethnicities, mirabegron decreased BAT fat fraction compared with placebo.

Conclusions

In South Asians and Europids, cold exposure and mirabegron induced beneficial metabolic effects. When combining both ethnicities, cold exposure and mirabegron increased REE and lipid oxidation, coinciding with a higher supraclavicular skin temperature and lower BAT fat fraction.

SUBMITTER: Nahon KJ

PROVIDER: S-EPMC7771034 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

The effect of mirabegron on energy expenditure and brown adipose tissue in healthy lean South Asian and Europid men.

Nahon Kimberly J KJ Janssen Laura G M LGM Sardjoe Mishre Aashley S D ASD Bilsen Manu P MP van der Eijk Jari A JA Botani Kani K Overduin Lisanne A LA Ruiz Jonatan R JR Burakiewicz Jedrzej J Dzyubachyk Oleh O Webb Andrew G AG Kan Hermien E HE Berbée Jimmy F P JFP van Klinken Jan-Bert JB van Dijk Ko Willems KW van Weeghel Michel M Vaz Frédéric M FM Coskun Tamer T Jazet Ingrid M IM Kooijman Sander S Martinez-Tellez Borja B Boon Mariëtte R MR Rensen Patrick C N PCN

Diabetes, obesity & metabolism 20200729 11

<h4>Aim</h4>To compare the effects of cold exposure and the β3-adrenergic receptor agonist mirabegron on plasma lipids, energy expenditure and brown adipose tissue (BAT) activity in South Asians versus Europids.<h4>Materials and methods</h4>Ten lean Dutch South Asian (aged 18-30 years; body mass index [BMI] 18-25 kg/m<sup>2</sup> ) and 10 age- and BMI-matched Europid men participated in a randomized, double-blinded, cross-over study consisting of three interventions: short-term (~ 2 hours) cold ...[more]

PMID: 32558052

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Project description:Aims/hypothesisIndividuals of South Asian origin are at increased risk of developing type 2 diabetes mellitus and associated comorbidities compared with Europids. Disturbances in energy metabolism may contribute to this increased risk. Skeletal muscle and possibly also brown adipose tissue (BAT) are involved in human energy metabolism and nitric oxide (NO) is suggested to play a pivotal role in regulating mitochondrial biogenesis in both tissues. We aimed to investigate the effects of 6 weeks of supplementation with L-arginine, a precursor of NO, on energy metabolism by BAT and skeletal muscle, as well as glucose metabolism in South Asian men compared with men of European descent.MethodsWe included ten Dutch South Asian men (age 46.5 ± 2.8 years, BMI 30.1 ± 1.1 kg/m2) and ten Dutch men of European descent, that were similar with respect to age and BMI, with prediabetes (fasting plasma glucose level 5.6-6.9 mmol/l or plasma glucose levels 2 h after an OGTT 7.8-11.1 mmol/l). Participants took either L-arginine (9 g/day) or placebo orally for 6 weeks in a randomised double-blind crossover study. Participants were eligible to participate in the study when they were aged between 40 and 55 years, had a BMI between 25 and 35 kg/m2 and did not have type 2 diabetes. Furthermore, ethnicity was defined as having four grandparents of South Asian or white European origin, respectively. Blinding of treatment was done by the pharmacy (Hankintatukku) and an independent researcher from Leiden University Medical Center randomly assigned treatments by providing a coded list. All people involved in the study as well as participants were blinded to group assignment. After each intervention, glucose tolerance was determined by OGTT and basal metabolic rate (BMR) was determined by indirect calorimetry; BAT activity was assessed by cold-induced [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography-computed tomography scanning. In addition, a fasting skeletal muscle biopsy was taken and analysed ex vivo for respiratory capacity using a multisubstrate protocol. The primary study endpoint was the effect of L-arginine on BAT volume and activity.ResultsL-Arginine did not affect BMR, [18F]FDG uptake by BAT or skeletal muscle respiration in either ethnicity. During OGTT, L-arginine lowered plasma glucose concentrations (AUC0-2 h - 9%, p < 0.01), insulin excursion (AUC0-2 h - 26%, p < 0.05) and peak insulin concentrations (-26%, p < 0.05) in Europid but not South Asian men. This coincided with enhanced cold-induced glucose oxidation (+44%, p < 0.05) in Europids only. Of note, in skeletal muscle biopsies several respiration states were consistently lower in South Asian men compared with Europid men.Conclusions/interpretationL-Arginine supplementation does not affect BMR, [18F]FDG uptake by BAT, or skeletal muscle mitochondrial respiration in Europid and South Asian overweight and prediabetic men. However, L-arginine improves glucose tolerance in Europids but not in South Asians. Furthermore, South Asian men have lower skeletal muscle oxidative capacity than men of European descent.FundingThis study was funded by the EU FP7 project DIABAT, the Netherlands Organization for Scientific Research, the Dutch Diabetes Research Foundation and the Dutch Heart Foundation.Trial registrationClinicalTrials.gov NCT02291458.

Dataset Information

The effect of mirabegron on energy expenditure and brown adipose tissue in healthy lean South Asian and Europid men.

Aim

Materials and methods

Results

Conclusions

Publications

The effect of mirabegron on energy expenditure and brown adipose tissue in healthy lean South Asian and Europid men.

Similar Datasets

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