Short Chain Fatty Acids and Their Receptors: New Metabolic Targets

Fatty acids are carboxylic acids with aliphatic tails of different lengths, where short chain fatty acids (SCFAs) typically refer to carboxylic acids with aliphatic tails less than 6 carbons. In humans, SCFAs are derived in large part from fermentation of carbohydrates and proteins in the colon. By this process, the host is able to salvage energy from foods that cannot be processed normally in the upper parts of the gastrointestinal tract. In humans, SCFAs are a minor nutrient source, especially for people on Western diets. Intriguingly, recent studies, as highlighted here, have described multiple beneficial roles of SCFAs in the regulation of metabolism. Further interest in SCFAs has emerged due to the association of gut flora composition with obesity and other metabolic states. The recent identification of receptors specifically activated by SCFAs has further increased interest in this area. These receptors, free fatty acid receptor-2 and -3 (FFAR2 and FFAR3), are expressed not only in the gut epithelium where SCFAs are produced, but also at multiple other sites considered to be metabolically important, such as adipose tissue and pancreatic islets. Because of these relatively recent findings, studies examining the role of these receptors, FFAR2 and FFAR3, and their ligands, SCFAs, in metabolism are emerging. This review provides a critical analysis of SCFAs, their recently identified receptors, and their connection to metabolism.