Acylation of ghrelin is increased in heart failure and decreases post heart transplantation

Objectives. Ghrelin is an anabolic hormone that is elevated in heart failure (HF), with resistance to its anabolic effects. This resolves after heart transplantation (HTx). Ghrelin exists in acylated and des-acyl forms, with the acylated form being primarily responsible for endocrine actions. We tested the hypothesis that ghrelin derangements in HF are due to inadequate acylation and that this resolves post transplantation. Design. Plasma levels of des-acyl and acylated ghrelin and acylated/total ratios were assessed in HF (n = 20), post-HTx (n = 35), and healthy controls (n = 4), and correlated with each other and with clinical parameters. Results. Median (interquartile range) of des-acyl ghrelin level, was 167 (121-195) pg/ml in HF versus 149 (130-223) pg/ml in post-HTx, p = NS. Acylated ghrelin level was 76 (51-99) pg/ml versus 13 (0-30) pg/ml, p < 0.001. Acylated/total ratios were 0.33 (0.20-0.47) versus 0.08 (0-0.13), p < 0.001. The correlation between acylated and total ghrelin levels was greater in HF than that in HTx. Acyl ghrelin correlated inversely with body mass index in HF, but not in HTx. Conclusion. Acylated ghrelin and the acylated/total ratio were dramatically higher in HF compared with those in HTx. Acylation rather than secretion of ghrelin is upregulated in HF and the resistance to ghrelin's anabolic and appetite-stimulating effects is not at the level of acylation, but downstream at the ghrelin-receptor level.