Sympathetic tone dictates the impact of lipolysis on FABP4 secretion.

Content Provider	Europe PMC
Author	Prentice, Kacey J. Lee, Alexandra Cedillo, Paulina Inouye, Karen E. Ertunc, Meric Erikci Riveros, Jillian K. Lee, Grace Yankun Hotamisligil, Gökhan S.
Copyright Year	2023
Abstract	Levels of circulating fatty acid binding protein 4 (FABP4) protein are strongly associated with obesity and metabolic disease in both mice and humans, and secretion is stimulated by β-adrenergic stimulation both in vivo and in vitro. Previously, lipolysis-induced FABP4 secretion was found to be significantly reduced upon pharmacological inhibition of adipose triglyceride lipase (ATGL) and was absent from adipose tissue explants from mice specifically lacking ATGL in their adipocytes (ATGLAdpKO). Here, we find that upon activation of β-adrenergic receptors in vivo, ATGLAdpKO mice unexpectedly exhibited significantly higher levels of circulating FABP4 as compared with ATGLfl/fl controls, despite no corresponding induction of lipolysis. We generated an additional model with adipocyte-specific deletion of both FABP4 and ATGL (ATGL/FABP4AdpKO) to evaluate the cellular source of this circulating FABP4. In these animals, there was no evidence of lipolysis-induced FABP4 secretion, indicating that the source of elevated FABP4 levels in ATGLAdpKO mice was indeed from the adipocytes. ATGLAdpKO mice exhibited significantly elevated corticosterone levels, which positively correlated with plasma FABP4 levels. Pharmacological inhibition of sympathetic signaling during lipolysis using hexamethonium or housing mice at thermoneutrality to chronically reduce sympathetic tone significantly reduced FABP4 secretion in ATGLAdpKO mice compared with controls. Therefore, activity of a key enzymatic step of lipolysis mediated by ATGL, per se, is not required for in vivo stimulation of FABP4 secretion from adipocytes, which can be induced through sympathetic signaling.
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ISSN	00222275
Journal	Journal of Lipid Research [J Lipid Res]
Volume Number	64
DOI	10.1016/j.jlr.2023.100386
PubMed Central reference number	PMC10248869
Issue Number	6
PubMed reference number	37172691
e-ISSN	15397262
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2023-05-10
Access Restriction	Open
Rights License	This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). © 2023 The Authors
Subject Keyword	lipolysis adipocytes adipose tissue adipose triglyceride lipase fatty acid binding proteins fatty acid transport sympathetic tone
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Endocrinology