Endocrine Abstracts

Ghrelin requires a fatty acid modification for binding to the GH secretagogue receptor. Octanoylation of the Ser3 residue of ghrelin is essential for ghrelin-mediated stimulation of GH secretion and regulation of energy homeostasis via increased food intake and adiposity. Other than octanoylation (C8:0), the hormone is subject to other types of acyl modification, decanoylation (C10:0), and possibly decenoylation (C10:1). The fatty acid substrate that contributes to ghrelin acylation, however, has not been clarified, although the presumed donor is acyl-CoA. Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency causes elevated serum octanoylcarnitine levels, reflecting elevated octanoyl-CoA levels. Glutaric aciduria type II (GA2) is characterized by elevated serum acylcarnitine levels, including octanoyl carnitine. We hypothesized that acyl-CoA is the fatty acid substrate for ghrelin acylation. Because serum octanoyl-CoA levels are altered in these disorders, we examined blood levels of acyl (A) and desacyl (D) forms of ghrelin in affected patients. Plasma acyl ghrelin levels and A/D ratios appeared to be elevated in patients with MCAD deficiency or GA2 in comparison to those in normal subjects. Reverse-phase high-performance liquid chromatography confirmed that n-octanoylated ghrelin levels were elevated in these patients. In addition, serum C10-acylcarnitine levels were also elevated in patients with GA2. In conclusion, changing serum medium-chain acylcarnitine levels may affect circulating acyl ghrelin levels, suggesting that acyl-CoA is the substrate for ghrelin acylation. Moreover, acylation of ghrelin may be linked to energy homeostasis and fat metabolism. In other words, ghrelin may play an important role in metabolic balance via its own fatty acid metabolism. Finally, our results may have pathophysiologic implications for these disorders. Alterations of plasma ghrelin levels in these disorders may reflect and/or influence the patient’s metabolic status.

Declaration of interest: I fully declare a conflict of interest. Details below.

Funding: This work was supported, however funding details unavailable.

This study was supported by funds from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Ministry of Health, Labour and Welfare of Japan; the Tokyo Biochemical Research Foundation; and the Foundation for Growth Science.