Ghrelin interacts with human plasma lipoproteins.
Ghrelin, a peptide hormone produced predominantly by the stomach, stimulates food intake and GH secretion. The Ser(3) 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), whereas 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 (LDLs) and lipoprotein-poor plasma subfractions. Butyrylcholinesterase and platelet-activating factor acetylhydrolase (EC 3.1.1.47) were responsible for the ghrelin hydrolytic activity of the lipoprotein-poor plasma and LDL subfractions, respectively. Moreover, we observed that ghrelin is associated with triglyceride-rich lipoproteins (TRLs), high-density lipoproteins (HDLs), very high-density lipoproteins (VHDLs), and to some extent LDLs. In conclusion, we report that the presence of the acyl group is necessary for ghrelin interaction with TRLs and LDLs but not HDLs and VHDLs. Ghrelin interacts via its N- and C-terminal parts with HDLs and VHDLs. This suggests that, whereas TRLs mostly transport acylated ghrelin, HDLs and VHDLs transport both ghrelin and des-acyl ghrelin.
De Vriese
Carine
C
Department of Biochemistry and Nutrition, Faculty of Medicine, Université Libre de Bruxelles, B-1070 Brussels, Belgium.
Hacquebard
Mirjam
M
Gregoire
Françoise
F
Carpentier
Yvon
Y
Delporte
Christine
C
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood; D000215:Acylation; D000328:Adult; D002091:Butyrylcholinesterase / Q000097:blood; D002210:Caprylates / Q000097:blood; D002846:Chromatography, Affinity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D054439:Ghrelin; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D036361:Peptide Hormones / Q000097:blood* / Q000737:chemistry; D010972:Platelet Activating Factor / Q000378:metabolism; D017434:Protein Structure, Tertiary; D014280:Triglycerides / Q000097:blood
D002210:Caprylates; D004791:Enzyme Inhibitors; D054439:Ghrelin; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D036361:Peptide Hormones; D010972:Platelet Activating Factor; D014280:Triglycerides; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D002091:Butyrylcholinesterase; C031492:octanoic acid