Investigating the innervation and neurogenic activation of lipolysis in white adipose tissue

Goddard, Kayleigh (2024) Investigating the innervation and neurogenic activation of lipolysis in white adipose tissue. Doctoral thesis, University of East Anglia.

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Abstract

Obesity is a growing global concern and research is key to developing understanding and mitigative strategies. Metabolic research often involves in vitro culture using cell lines or isolated primary adipocytes, offering limited translatability to in vivo physiology, as adipose is heterogeneous, with dense vascularisation and rich nervous innervation. However, nervous innervation of white adipose tissue (WAT) has not been fully resolved, with literature offering contradictory reports on the frequency and type of nerve-adipocyte interactions.

Here, adopting an alternative method of whole-mount immunocytochemistry, I present evidence of nervous innervation of mouse subcutaneous WAT (SAT) in three major modes: in coarse bundles, innervating vasculature, and parenchymal innervation, including direct adipocyte-encapsulating structures. Contrary to other reports, instances of direct nerve-adipocyte interactions were occasional, and were exclusively sympathetic. These casual sympathetic interactions are sufficient for inducing lipolysis, as in a novel neurogenic approach, the use of Na+-channel opener veratridine to stimulate nerves ex vivo in SAT, successfully induced lipolysis to equivalent levels of norepinephrine. Contrary to literature in rodents, the β2-adrenergic receptor (AR), not β3-AR, was found critical to veratridine-driven lipolysis, which presents a novel finding. Pharmacological characterisation indicated norepinephrine as the sole driver of veratridine-evoked lipolysis, with sensory neuropeptides and other sympathetic neurotransmitters neuropeptide (NPY) and adenosine triphosphate (ATP), uninfluential in lipolysis. Interrogating the role of purinergic signalling further, there was no role for identified P2X4 and P2Y6 receptors in regulating either stimulated, or basal lipolysis.

These data serve to improve understanding of murine SAT innervation, as well as signalling molecules involved in regulating lipolysis in a model likely more representative of physiology. The investigation into innervation and lipolysis using these approaches could be further developed in rodent, but also human adipose, for study across obese & diabetic states and to investigate other outcomes including lipogenesis, and adipokine secretion. The ex vivo platform incorporating veratridine-induced lipolysis could be harnessed for research and development in preclinical trials.

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Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Kitty Laine
Date Deposited:	28 Mar 2025 11:24
Last Modified:	28 Mar 2025 11:24
URI:	https://ueaeprints.uea.ac.uk/id/eprint/98898
DOI:

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