SFEBES2023 Oral Communications Metabolism, Obesity and Diabetes (6 abstracts)
Human brown adipose tissue activity is regulated by the parasympathetic nervous system
T’ng Choong Kwok 1 , Lynne E. Ramage 1 , Calum Gray 1 , Sonia J. Wakelin 2 , Edwin JR van Beek 1 , Alexandra Kelman 1 , Robert J. Semple 1 , Karla J. Suchacki 1 & Roland H Stimson 1
1University of Edinburgh, Edinburgh, United Kingdom. 2Royal Infirmary Edinburgh, Edinburgh, United Kingdom
Brown adipose tissue (BAT) is a therapeutic target for obesity and associated metabolic diseases, due to its role in non-shivering thermogenesis. BAT activation is mediated through sympathetic stimulation, but parasympathetic regulation of human BAT has not been demonstrated previously. We undertook RNA sequencing of human white and brown primary adipocytes to identify novel pathways regulating BAT. CHRM2 (encoding the muscarinic acetylcholine receptor 2) was the most differentially expressed gene (~50-fold higher in human brown than white adipocytes) and was not expressed in murine brown or beige adipocytes. In addition, immunohistochemistry revealed higher CHRM2 expression in human BAT than WAT. To identify parasympathetic regulation of BAT in vivo, 15 healthy volunteers (26.4±1.3 years, BMI 22.2±0.4 kg/m2) received oxybutynin (a CHRM antagonist) 15mg daily or placebo for 4 days in a randomised double-blind crossover study. At the end of each phase, participants were housed in a warm room (23-24°C) for 1 hour, followed by mild cold exposure (16-17°C) for 3 hours to activate BAT. BAT activity was measured using 18F-fluorodeoxyglucose-positron emission tomography magnetic resonance scanning (18F-FDG-PET/MR) during cold exposure. Supraclavicular skin temperature and energy expenditure were measured during warm and cold conditions. Oxybutynin reduced 18F-FDG uptake by BAT by ~20% (P<0.01) and BAT volume by ~25% (P<0.05) without altering BAT fat fraction. Energy expenditure increased following cold exposure only during the placebo phase. Supraclavicular skin temperature during warm and cold exposure were similar between phases. Cold exposure increased free fatty acid and noradrenaline levels similarly during placebo and oxybutynin phases, indicating adequate and equal sympathetic stimulation on both phases with cold exposure. These data suggest that the parasympathetic system activates human BAT through CHRM2 and reveals novel species-specific differences in the regulation of BAT. Further work is required to determine the mechanisms through which CHMR2 activates human BAT.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more