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ToolsGoddard, Kayleigh E. and Fountain, Samuel J. (2025) Characterisation of neurogenic lipolytic responses in white adipose tissue ex vivo. British Journal of Pharmacology. ISSN 0007-1188
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Abstract
Background and Purpose: Dysfunction of the autonomic nervous system is associated with cardiovascular dysfunction, including metabolic syndrome and obesity. Understanding mechanisms of neurogenic control of white adipose tissue is key to understanding adipose physiology and pathophysiology, though there is limited research exploring this in adipose tissue using pharmacological tools, as opposed to genetic knockout models. Experimental Approach: Inguinal white adipose tissue from C57BL/6J mice was used in this study. We used immunocytochemistry to determine tissue innervation and glycerol release assays to quantify lipolysis in adipose tissue and isolated adipocytes. The voltage-gated Na+ channel opener veratridine was used to stimulate nervous activity in tissue ex vivo. The role of neurotransmitters and receptors mediating veratridine-evoked lipolysis in adipose tissue was pharmacologically characterised. Key Results: Veratridine evoked glycerol release in white adipose tissue but not from isolated adipocytes. This release was abolished by tetrodotoxin and propranolol. Veratridine also induced noradrenaline release from white adipose tissue. Veratridine- and noradrenaline-evoked glycerol release was blocked by the β2-adrenoceptor antagonist ICI-118551 but not by the β1-adrenoceptor antagonist CGP 20712A. Purported β3-adrenoceptor antagonists L-748337 and SR59230A stimulated glycerol release from tissue and from isolated adipocytes. Neither L-748337 or SR59230A antagonised veratridine-evoked glycerol release but SR59230A antagonised noradrenaline-evoked glycerol release. We exclude contributions of sensory neuropeptides and the autonomic neurotransmitters neuropeptide Y and ATP. Conclusion and Implications: Neurogenic lipolytic responses can be measured in white adipose tissue ex vivo using veratridine to stimulate nerve activity. The lipolytic responses are mediated by β2-adrenoceptor activation. This study provides the first evidence of neurogenic lipolysis in tissue ex vivo.
| Item Type: | Article |
|---|---|
| Additional Information: | DATA AVAILABILITY STATEMENT: The data that support the findings of this study are available from the corresponding author upon reasonable request. ACKNOWLEDGEMENTS: This work was funded by the Biotechnology and Biological Sciences Research Council and the British Heart Foundation (PG/19/35/34389). |
| Uncontrolled Keywords: | adipose,neurogenic,neurotransmitter,obesity,pharmacology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/3000/3004 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Science > Research Groups > Cells and Tissues |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 21 Feb 2025 14:30 |
| Last Modified: | 28 Mar 2025 13:13 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/98560 |
| DOI: | 10.1111/bph.17445 |
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