期刊
PHYSIOLOGICAL REPORTS
卷 10, 期 16, 页码 -出版社
WILEY
DOI: 10.14814/phy2.15424
关键词
conditioned media; IMAT; inflammation; insulin sensitivity; paracrine signaling
类别
资金
- National Institutes of Health [F31DK126393, P30DK048520, R01DK111559, R01DK118149, RR-00036]
Adipose tissue, especially intermuscular adipose tissue (IMAT), secretes various mediators that have local and systemic effects on metabolic regulation. IMAT has a distinct secretome compared to subcutaneous (SAT) and visceral adipose tissue (VAT), including more cytokines, chemokines, adipokines, and eicosanoids. This study suggests that IMAT may play a critical role in glucose regulation and insulin resistance in the context of obesity.
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, IFN gamma 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 (PGE(2,) 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.
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