Aim: 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. Materials and Methods: Ten lean Dutch South Asian (aged 18-30 years; body mass index [BMI] 18-25 kg/m 2) 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

Brown adipose tissue (BAT) improves energy metabolism by combusting glucose and lipids into heat. Agonism of the glucagon-like peptide-1 receptor (GLP-1R) within the central nervous system activates BAT in mice. Moreover, in patients with type 2 diabetes, GLP-1R agonism lowers body weight and improves glucose and lipid levels, possibly involving BAT activation. Interestingly, people from South Asian descent are prone to develop cardiometabolic disease. We studied the effect of GLP-1R agonism on BAT in humans, specifically in South Asians and Europids without obesity or type 2 diabetes. Methods: Twelve Dutch South Asian and 12 age-and BMI-matched Europid nondiabetic men received 12 weeks extended-release exenatide (Bydureon) in this single-arm prospective study. Before and after treatment, BAT was visualized by a cold-induced [ 18 F]FDG-PET/CT scan and a thermoneutral MRI scan, and resting energy expenditure (REE), substrate oxidation, body composition and fasting plasma glucose and serum lipids were determined. Appetite was rated using a visual analogue scale. Results: Since the effect of exenatide on metabolic parameters did not evidently differ between ethnicities, data of all participants were pooled. Exenatide decreased body weight (−1.5 ± 0.4 kg, p b 0.01), without affecting REE or substrate oxidation, and transiently decreased appetite ratings during the first weeks. Exenatide also lowered triglycerides (−15%, p b 0.05) and total cholesterol (−5%, p b 0.05), and tended to lower glucose levels. Notably, exenatide increased BAT metabolic volume (+28%, p b 0.05) and mean standardized uptake value (+11%, p b 0.05) ([ 18 F]FDG-PET/CT), without affecting supraclavicular adipose tissue fat fraction (MRI). Conclusions/interpretation: We show for the first time that GLP-1R agonism increases [ 18 F]FDG uptake by BAT in South Asian and Europid men without obesity or type 2 diabetes. Trial registry: Clinicaltrials.gov NCT03002675.

Introduction/Aims: Becker muscular dystrophy (BMD) is characterized by variable disease severity and progression, prompting the identification of biomarkers for clinical trials. We used data from an ongoing phase II study to provide a comprehensive characterization of a cohort of patients with BMD, and to assess correlations between histological and magnetic resonance imaging (MRI) markers with muscle function and strength. Methods: Eligible patients were ambulatory males with BMD, aged 18 to 65 years (200 to 450 meters on 6-minute walk test). The following data were obtained: function test results, strength, fat-fraction quantification using chemical shift-encoded MRI (whole thigh and quadriceps), and fibrosis and muscle fiber area (MFA) of the brachial biceps. Results: Of 70 patients screened, 51 entered the study. There was substantial heterogeneity between patients in muscle morphology (histology and MRI), with high fat replacement. Total fibrosis correlated significantly and mostly moderately with all functional endpoints, including both upper arm strength assessments (left and right elbow flexion rho À.574 and À.588, respectively [both P < .0001]), as did MRI fat fraction (whole thigh and quadriceps), for example, with four-stair-climb velocity À.554 and À.550, respectively (both P < .0001). Total fibrosis correlated significantly and moderately with both MRI fat fraction assessments (.500 [P = .0003] and .423 [.0024], respectively).

Highlights 7T MRS separately measured glutamate, glutamine and GABA towards triggered attacks. Visual cortex GABA levels increased towards a preictal migraine state. Visual cortex glutamate and glutamine levels were stable across migraine states.