Fig. 2.

Molecular mechanisms of SCFAs signaling. Outside of the cell, SCFAs function as agonists for G-protein-coupled receptors (GPCRs), including GPR41, GPR43, and GPR109A. SCFAs stimulation of GPCRs activates the mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs), and nuclear factor-κB (NF-κB) pathways. In addition to acting as a ligand for GPCRs on the cell surface, SCFAs can enter cells via several monocarboxylate transporters such as hydrogen-coupled transporters (MCT1, MCT4), and sodium-coupled monocarboxylate transporters (SMCT1). Intracellular SCFAs can promote gene transcription by inhibiting histone deacetylases (HDACs) and activating histone acetyltransferases (HATs). These processes can occur in colonocytes as well as in any cell within a tissue accessible to SCFAs