Short-chain fatty acid receptors and histone deacetylase enzymes (SCFA-R/HDAC)

Short-chain fatty acid (SCFA) receptors and histone deacetylase (HDAC) enzymes represent a dual-action signaling system primarily activated by microbial fermentation products like acetate, propionate, and butyrate. The SCFA receptors, including Free Fatty Acid Receptor 2 (FFAR2/GPR43), Free Fatty Acid Receptor 3 (FFAR3/GPR41), and Hydroxycarboxylic Acid Receptor 2 (HCAR2/GPR109A), are G protein-coupled receptors that mediate immune modulation and metabolic homeostasis (Brown et al., 2003, J Biol Chem). Concurrently, SCFAs—particularly butyrate—function as endogenous inhibitors of HDACs, specifically Class I and IIa, thereby promoting histone hyperacetylation and regulating the expression of genes involved in apoptosis and cell differentiation (Davie, 2003, J Nutr). This integrated axis is vital for maintaining intestinal epithelial integrity and suppressing colonic inflammation (Tan et al., 2014, Adv Immunol). Dysregulation of this system is linked to various pathologies, including colorectal cancer, inflammatory bowel disease (IBD), and obesity-related metabolic disorders. Pharmacological intervention targets this axis through the development of selective GPCR agonists or HDAC inhibitors to treat inflammatory and oncological conditions (Vinolo et al., 2011, Nutrients).

Other names

Short-chain fatty acid receptorsFree fatty acid receptorsFFARsHistone deacetylasesHDACsButyrate receptorsGPR41GPR43GPR109AFFAR2FFAR3HCAR2

Activation of G protein-coupled receptors (GPR41, GPR43, GPR109A) and inhibition of histone deacetylase (HDAC) enzymes.