Laura G M Janssen1, Kimberly J Nahon1, Katrien F M Bracké1, Dennis van den Broek1, Renée Smit1, Aashley S D Sardjoe Mishre2, Lisa L Koorneef1, Borja Martinez-Tellez3, Jedrzej Burakiewicz2, Hermien E Kan2, Floris H P van Velden4, Lenka M Pereira Arias-Bouda5, Lioe-Fee de Geus-Oei6, Jimmy F P Berbée1, Ingrid M Jazet7, Mariëtte R Boon8, Patrick C N Rensen1. 1. Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands. 2. Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, the Netherlands. 3. Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands; PROFITH (PROmoting FITness and Health Through Physical Activity) Research Group, Department of Physical Education and Sports, Faculty of Sport Sciences, University of Granada, Granada, Spain. 4. Department of Radiology, Division of Nuclear Medicine, Leiden University Medical Center, Leiden, the Netherlands. 5. Department of Radiology, Division of Nuclear Medicine, Leiden University Medical Center, Leiden, the Netherlands; Department of Nuclear Medicine, Alrijne Hospital, Leiderdorp, the Netherlands. 6. Department of Radiology, Division of Nuclear Medicine, Leiden University Medical Center, Leiden, the Netherlands; Biomedical Photonic Imaging Group, University of Twente, Enschede, the Netherlands. 7. Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands. 8. Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: m.r.boon@lumc.nl.
Abstract
AIMS/HYPOTHESIS: 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 [18F]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 < 0.01), without affecting REE or substrate oxidation, and transiently decreased appetite ratings during the first weeks. Exenatide also lowered triglycerides (-15%, p < 0.05) and total cholesterol (-5%, p < 0.05), and tended to lower glucose levels. Notably, exenatide increased BAT metabolic volume (+28%, p < 0.05) and mean standardized uptake value (+11%, p < 0.05) ([18F]FDG-PET/CT), without affecting supraclavicular adipose tissue fat fraction (MRI). CONCLUSIONS/ INTERPRETATION: We show for the first time that GLP-1R agonism increases [18F]FDG uptake by BAT in South Asian and Europid men without obesity or type 2 diabetes. TRIAL REGISTRY: Clinicaltrials.gov NCT03002675.
AIMS/HYPOTHESIS: 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 [18F]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 < 0.01), without affecting REE or substrate oxidation, and transiently decreased appetite ratings during the first weeks. Exenatide also lowered triglycerides (-15%, p < 0.05) and total cholesterol (-5%, p < 0.05), and tended to lower glucose levels. Notably, exenatide increased BAT metabolic volume (+28%, p < 0.05) and mean standardized uptake value (+11%, p < 0.05) ([18F]FDG-PET/CT), without affecting supraclavicular adipose tissue fat fraction (MRI). CONCLUSIONS/ INTERPRETATION: We show for the first time that GLP-1R agonism increases [18F]FDG uptake by BAT in South Asian and Europid men without obesity or type 2 diabetes. TRIAL REGISTRY: Clinicaltrials.gov NCT03002675.
Authors: Mila S Welling; Cornelis J de Groot; Lotte Kleinendorst; Bibian van der Voorn; Jan Steven Burgerhart; Eline S van der Valk; Mieke M van Haelst; Erica L T van den Akker; Elisabeth F C van Rossum Journal: Clin Obes Date: 2021-07-21
Authors: Fernanda C B Oliveira; Eduarda J Bauer; Carolina M Ribeiro; Sidney A Pereira; Bruna T S Beserra; Simone M Wajner; Ana L Maia; Francisco A R Neves; Michella S Coelho; Angelica A Amato Journal: Front Endocrinol (Lausanne) Date: 2022-01-04 Impact factor: 5.555