Free fatty acid receptor 2

Free fatty acid receptor 2 (FFAR2), also termed G-protein coupled receptor 43 (GPR43), is a rhodopsin-like G-protein coupled receptor (also termed GPR or GPCR). It is coded (i.e., its synthesis is directed) by the FFAR2 gene. (FFAR2 and Ffar2 are used respectively to designate the human and animal genes for FFAR2.) In humans, the FFAR2 gene is located on the long (i.e., "q") arm of chromosome 19 at position 13.12 (location notated as 19q13.12). Like other GPCRs, FFAR2s reside on the surface membrane of cells and when bond to one of their activating ligands regulate the function of their parent cells. FFAR2 is a member of a small family of structurally and functionally related GPRs termed free fatty acid receptors (FFARs). This family includes three other receptors which, like FFAR2, are activated by certain fatty acids: FFAR1 (also termed GPR40), FFAR3 (GPR41), and FFAR4 (GPR120). FFAR2 and FFAR3 are activated by short-chain fatty acids whereas FFAR1 and FFAR4 are activated by long-chain fatty acids.

Short-chain fatty acids (i.e., SCFAs) are made by intestinal bacteria (intestinal and intestine are used here to mean the small intestine plus the large intestine's longest portion, the colon). These SCFAs are excreted from the bacteria, enter the hosts tissues, and stimulate cells in these tissues. This stimulation regulates many normal body functions but may result in the inhibition or promotion of various diseases and disorders. The types of bacteria in the intestines can be modified to increase the number of bacteria that make SCFAs by using foods that stimulate the growth of these bacteria (i.e., prebiotics), preparations of SCFA-producing bacteria (i.e., probiotics), or both methods (i.e., synbiotics). Individuals with diseases or disorders that are associated with low levels of the SCFA-producing intestinal bacteria may show improvements in their conditions when treated with prebiotics, probiotics, or synbiotics while individuals with diseases or disorders associated with high levels of SCFAs may show improvements in their conditions when treated with methods, e.g., antibiotics, that reduce the intestinal levels of these bacteria. It is now known that FFAR2 is activated by SCFAs and therefore may function not only in regulating normal body functions but also in inhibiting or promoting many diseases and disorders. Consequently, drugs are being tested for their ability to act more usefully, potently, and effectively than SCFAs to stimulate or inhibit FFAR2 for treating the conditions that appear inhibited or stimulated, respectively, by SCFAs.

Studies have suggested that SCFA-activated FFAR2 regulates blood insulin and glucose levels, inflammation, the development of fat tissues, blood levels of fatty acids, the growth of certain cancerous and non-cancerous cells, and the infectiveness and severity of certain bacteria and viruses. As a result of these actions, FFAR2 may promote or inhibit the development and/or progression of diabetes, inflammatory reactions, obesity, ketoacidosis (i.e., life-threatening increases in blood acidity due to diabetes, starvation, excessive alcohol intake, certain medications, or certain toxins), some types of cancer, maturation of microglia (i.e., immune) cells in the brain and spinal cord, certain neurological diseases, and certain bacterial and viral infections. Here, we review studies on the functions of FFAR2 in health as well as these diseases and disorders.