Quantifying the inflammatory secretome of human intermuscular adipose tissue.

Abstract

Adipose tissue secretes an abundance of lipid and protein mediators, and this secretome is depot-specific, with local and systemic effects on metabolic regulation. Intermuscular adipose tissue (IMAT) accumulates within the skeletal muscle compartment in obesity, and is associated with insulin resistance and metabolic disease. While the human IMAT secretome decreases insulin sensitivity in vitro, its composition is entirely unknown. The current study was conducted to investigate the composition of the human IMAT secretome, compared to that of the subcutaneous (SAT) and visceral adipose tissue (VAT) depots. IMAT, SAT, and VAT explants from individuals with obesity were used to generate conditioned media. Proteomics analysis of conditioned media was performed using multiplex proximity extension assays, and eicosanoid analysis using liquid chromatography-tandem mass spectrometry. Compared to SAT and/or VAT, IMAT secreted significantly more cytokines (IL2, IL5, IL10, IL13, IL27, FGF23, IFNγ and CSF1) and chemokines (MCP1, IL8, CCL11, CCL20, CCL25 and CCL27). Adipokines hepatocyte growth factor and resistin were secreted significantly more by IMAT than SAT or VAT. IMAT secreted significantly more eicosanoids (PGE2, TXB2 , 5-HETE, and 12-HETE) compared to SAT and/or VAT. In the context of obesity, IMAT is a distinct adipose tissue with a highly immunogenic and inflammatory secretome, and given its proximity to skeletal muscle, may be critical to glucose regulation and insulin resistance.

• Authors: Darcy Kahn, Emily Macias, Simona Zarini, Amanda Garfield, Karin Zemski Berry, Robert Gerszten, Jonathan Schoen, Melanie Cree-Green, Bryan C Bergman
• Journal: Physiological reports (Physiol Rep) Vol. 10 Issue 16 Pg. e15424 (08 2022) ISSN: 2051-817X [Electronic] United States
• PMID: 35980018 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.

Chemical References

• Culture Media, Conditioned

Topics

• Adipose Tissue (metabolism)
• Culture Media, Conditioned
• Humans
• Insulin Resistance (physiology)
• Obesity (metabolism)
• Secretome