Β 2 AR Agonists Sustain Thermogenesis and Leanness via Sympathofacilitation

Samson W Cheung; David Sidarta-Oliveira; Lu Yao; Yitao Zhu; Gitalee Sarker; Sofia Lundh; Donald A Morgan; Ji Qu; Sian Wilcox; Vladyslav Vyazovskiy; David J Paterson; Dan Li; Kamal Rahmouni; Ana I Domingos

doi:10.1101/2025.06.13.659468

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Β 2 AR Agonists Sustain Thermogenesis and Leanness via Sympathofacilitation

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Β 2 AR Agonists Sustain Thermogenesis and Leanness via Sympathofacilitation

Samson W Cheung, David Sidarta-Oliveira, Lu Yao, Yitao Zhu, Gitalee Sarker, Sofia Lundh, Donald A Morgan, Ji Qu, Sian Wilcox, Vladyslav Vyazovskiy, …

bioRxiv

Cold Spring Harbor Laboratory

06/17/2025

DOI: 10.1101/2025.06.13.659468

PMCID: PMC12262434

PMID: 40666958

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https://doi.org/10.1101/2025.06.13.659468View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Human thermogenesis depends on β2-adrenoceptors (β2AR) expressed in thermogenic adipocytes, which are activated by norepinephrine released from sympathetic neurons. Whether β2AR also modulates thermogenesis via direct presynaptic action within sympathetic neurons has remained unclear. Here, we identify Adrb2 expression in human and rodent cervical sympathetic neurons. β2AR agonism exerts neurotrophic effects and facilitates cholinergic responsiveness in mouse sympathetic neurons, indicating a sympathofacilitatory role. Selective deletion of β2AR in sympathetic neurons leads to impaired nerve activity in brown adipose tissue, sympathetic neuropathy, worsened fasting-induced hypothermia, and progressive obesity in chow-fed mice—without changes in food intake. These findings uncover a presynaptic role for β2AR in sustaining thermogenesis and regulating adiposity, suggesting sympathofacilitation as a therapeutic avenue for obesity.

Details

Title: Subtitle: Β 2 AR Agonists Sustain Thermogenesis and Leanness via Sympathofacilitation
Creators: Samson W Cheung - University of Oxford
David Sidarta-Oliveira - University of Oxford
Lu Yao - University of Oxford
Yitao Zhu - University of Oxford
Gitalee Sarker - University of Oxford
Sofia Lundh - Novo Nordisk
Donald A Morgan - University of Iowa
Ji Qu - University of Oxford
Sian Wilcox - University of Oxford
Vladyslav Vyazovskiy - University of Oxford
David J Paterson - University of Oxford
Dan Li - University of Oxford
Kamal Rahmouni - University of Iowa
Ana I Domingos - University of Oxford
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.1101/2025.06.13.659468
PMID: 40666958
PMCID: PMC12262434
NLM abbreviation: bioRxiv
ISSN: 2692-8205
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory; United States
Language: English
Date posted: 06/17/2025
Academic Unit: Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984848017602771

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