Microenvironmental Stiffness Regulates Cellular Triglyceride Metabolism

The mechanics of the microenvironment, particularly the extracellular matrix, dictate cellular functions, including cell survival, apoptosis, proliferation, differentiation and many types of morphogenesis, through mechanosensing and mechanotransduction.  All these processes depend on the temporal balance in cellular metabolism; however, the mechanisms by which cell metabolism is controlled and adapted to changes in the mechanical environment are not completely clear.  Here, we report that mechanical stiffness mediates triglyceride (TG) metabolism in chondrocyte model.  Cellular TG contents were first shown to be coupled to mechanical stiffness. Specifically, the synthesis and lipolysis of TGs were mechanically regulated by fatty acid-binding protein 3 (FABP3) and cytochrome p450 1b1 (cyp1b1), respectively. The shift from synthesis to lipolysis was mediated by the regulatory FZD7-c-Myc-PPARα/PGC1 signaling axis. The final metabolomic analysis confirmed that the products identified were from TG metabolism. This study reveals crosstalk between microenvironment mechanics and lipid metabolism and identifies the key roles of mediators in this process.