Ghrelin, a peptide hormone produced predominantly by the stomach, stimulates food intake and growth hormone secretion. The Ser³ residue of ghrelin is mainly modified by a n-octanoic acid. In the human bloodstream, ghrelin circulates in two forms: octanoylated and desacylated. We previously demonstrated that ghrelin is desoctanoylated in human serum by butyrylcholinesterase (EC 3.1.1.8) and other esterase(s), while in rat serum only carboxylesterase (EC 3.1.1.1) is involved.

The aims of this study were to determine the role of lipoprotein-associated enzymes in ghrelin desoctanoylation and the role of lipoproteins in the transport of circulating ghrelin. Our results show that ghrelin desoctanoylation mostly occurred in contact with low-density lipoproteins (LDL) and lipoprotein-poor plasma (LPP) subfractions. Butyrylcholinesterase and platelet-activating factor acetylhydrolase (PAF-AH; EC 3.1.1.47) were responsible for the ghrelin hydrolytic activity of the LPP and LDL subfractions, respectively. Moreover, we observed that ghrelin is associated with triglyceride-rich lipoproteins (TRL), high-density lipoproteins (HDL), very high-density lipoproteins (VHDL), and to some extent LDL.

In conclusion, we report that the presence of the acyl group is necessary for ghrelin interaction with TRL and LDL but not with HDL and VHDL. Ghrelin interacts via its N- and C-terminal parts with HDL and VHDL. This suggests that, while TRL mostly transport acylated ghrelin, HDL and VHDL transport both ghrelin and des-acyl ghrelin.