The density of extracellular matrix proteins regulates inflammation and insulin signaling in adipocytes

Abstract 

Cells can not only sense the type of extracellular matrix (ECM) protein that is present in the microenvironment, but they can also sense its density. Here, we investigated the effects of ECM protein density on adipokine secretion and insulin signaling in adipocytes. To this end, 3T3-L1 adipocytes were cultured on the surface of polyacrylamide gels that were coated with gradient densities of a collagen type I and fibronectin mixture. We found that high density ECM causes a decrease in insulin signaling and adiponectin secretion, whereas the secretion of monocyte chemoattractant protein-1 (MCP-1) was increased via the activation of nuclear factor-κB (NF-κB). These results indicate that the density of the ECM directly regulates the inflammatory response and insulin sensitivity of adipocytes.

Structured summary

MINT-7992217: Irs1 (uniprotkb:P35569) physically interacts (MI:0915) with phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha (uniprotkb:P26450) by anti bait coimmunoprecipitation (MI:0006)

Abbreviations: ECM, extracellular matrix, NF-κB, nuclear factor-κB, MCP-1, monocyte chemoattractant protein-1, IRβ, β subunit of insulin receptor, IRS-1, insulin receptor substrate-1, p85-PI3K, p85 subunit of phosphatidylinositol-3-kinase, SDS–PAGE, sodium dodecyl sulfate–polyacrylamide gel electrophoresis, ECL, enhanced chemiluminescence, BCA, bicinchoninic acid, TGF-β1, transforming growth factor-β1, PAI-1, plasminogen activator inhibitor-1, HMW, high molecular weight, MMW, medium molecular weight, GLUT4, glucose transporter type 4, CS, Calf serum, FBS, fetal bovine serum, IBMX, 3-isobutyl-1-methylxanthine, TEMED, N,N,N′,N′-tetramethylethylenediamine, PBS, phosphate-buffered saline, FAK, focal adhesion kinase, ERK, extracellular signal-regulated kinase

Keywords: Extracellular matrix, Insulin sensitivity, Inflammation, Adiponectin, Monocyte chemoattractant protein-1, Adipocyte