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Endocrine Abstracts (2023) 94 OC6.4 | DOI: 10.1530/endoabs.94.OC6.4

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.

Volume 94

Society for Endocrinology BES 2023

Glasgow, UK
13 Nov 2023 - 15 Nov 2023

Society for Endocrinology 

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