Characterisation of neurogenic lipolytic responses in white adipose tissue ex vivo

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.