The two major different circulating forms of ghrelin that exist in rats and man are the acylated (or n-octanoylated, AG) and unacylated (or des-octanoylated or des-acylated, UAG). AG has a unique feature that is a post-translational esterification of a fatty (n-octanoic or, to a lesser extent, n-decanoic) acid on serine residue at position 3. Ghrelin O-acyltransferase (GOAT) is a membrane-bound enzyme responsible for this octanoylation by attaching an 8-carbon medium-chain fatty acid (MCFA) (octanoate) to serine 3 of ghrelin. This acylation is necessary for the activity of ghrelin. Animal data suggest that MCFAs provide substrate for GOAT and an increase in nutritional octanoate increases acyl-ghrelin.14
Ghrelin acylation is necessary for its actions via GHS-R1a. Normally, AG accounts for less than 10 % of the total ghrelin in the circulation. The majority of circulating ghrelin is UAG.15 UAG was first considered an inactive form of ghrelin, although accumulating evidence indicates that UAG can modulate metabolic activities of the ghrelin system either independently or in opposition to those of AG.16