Fatty acids are the ligands for a small family of G-protein-coupled receptors, the Free Fatty Acid receptors, and an unrelated receptor GPR120.

Free fatty acid receptor 1 (FFAR1/GPR40) is activated by both saturated and unsaturated medium to long-chain fatty acids while FFAR2 (GPR43) and FFAR3 (GPR41) are activated by short-chain fatty acids (carboxylates) with six or fewer carbon molecules. A fourth highly homologous receptor GPR42 is believed to be a pseudogene with intact open reading frame, but could be a functional gene in a significant fraction of the human population.

GPR120 is activated by long chain (C16-22) fatty acids.