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Quantifying the inflammatory secretome of human intermuscular adipose tissue
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Quantifying the inflammatory secretome of human intermuscular adipose tissue
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Quantifying the inflammatory secretome of human intermuscular adipose tissue
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Journal Article
Quantifying the inflammatory secretome of human intermuscular adipose tissue
2022
Overview
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.
Intermuscular adipose tissue (IMAT) is interlaced within the muscle compartment and is negatively associated with the metabolic syndrome. This is the first report of the composition of the human IMAT secretome. In obesity, the IMAT secretome is highly immunogenic, secreting a distinct combination of cytokines, chemokines, adipokines and eicosanoids that are associated with insulin sensitivity. This study highlights the potential significance of crosstalk between IMAT and skeletal muscle in the development of type 2 diabetes.
