Nass Ralf, Nikolayev Alexander, Liu Jianhua, Pezzoli Suzan S, Farhy Leon S, Patrie James, Gaylinn Bruce D, Heiman Mark, Thorner Michael O
Division of Endocrinology and Metabolism (R.N., J.L., S.S.P., L.S.F., B.D.G., M.O.T.), Department of Medicine, Center for Diabetes Technology (L.S.F.), and Department of Health Sciences (J.P.), University of Virginia, Charlottesville, Virginia 22908; and Eli Lilly (A.N., M.H.), Lilly Research Laboratories, Indianapolis, Indiana 46285.
J Clin Endocrinol Metab. 2015 Jan;100(1):E110-3. doi: 10.1210/jc.2014-1318.
Acyl-ghrelin is a 28-amino acid peptide released from the stomach. Ghrelin O-acyl transferase (GOAT) attaches 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.
To address the question of the source of substrate for acylation, we studied whether the decline in ghrelin acylation during fasting is associated with a decline in circulating MCFAs.
Eight healthy young men (aged 18-28 years, body mass index range, 20.6-26.2 kg/m(2)) had blood drawn every 10 minutes for acyl- and desacyl-ghrelin and every hour for free fatty acids (FFAs) during the last 24 hours of a 61.5-hour fast and during a fed day. FFAs were measured by a highly sensitive liquid chromatography-mass spectroscopy method. Acyl- and desacyl-ghrelin were measured in an in-house assay; the results were published previously. Ghrelin acylation was assessed by the ratio of acyl-ghrelin to total ghrelin.
With the exception of MCFAs C8 and C10, all other FFAs, the MCFAs (C6 and C12), and the long-chain fatty acids (C14-C18) significantly increased with fasting (P < .05). There was no significant association between the fold change in ghrelin acylation and circulating FFAs.
These results suggest that changes in circulating MCFAs are not linked to the decline in ghrelin acylation during fasting and support the hypothesis that acylation of ghrelin depends at least partially on the availability of gastroluminal MCFAs or the regulation of GOAT activity.
酰基胃饥饿素是一种由胃分泌的含28个氨基酸的肽。胃饥饿素O-酰基转移酶（GOAT）将一种含8个碳的中链脂肪酸（MCFA）（辛酸）连接到胃饥饿素的丝氨酸3上。这种酰化作用对胃饥饿素的活性至关重要。动物实验数据表明，MCFAs为GOAT提供底物，营养性辛酸的增加会使酰基胃饥饿素增加。
为解决酰化作用底物的来源问题，我们研究了禁食期间胃饥饿素酰化作用的下降是否与循环中的MCFAs下降有关。
8名健康年轻男性（年龄18 - 28岁，体重指数范围为20.6 - 26.2 kg/m²）在61.5小时禁食的最后24小时以及进食日期间，每10分钟采集一次血液用于检测酰基和去酰基胃饥饿素，每小时采集一次血液用于检测游离脂肪酸（FFA）。FFA通过高灵敏度液相色谱 - 质谱法进行检测。酰基和去酰基胃饥饿素通过内部检测方法进行测定；结果已在之前发表。胃饥饿素酰化作用通过酰基胃饥饿素与总胃饥饿素的比值进行评估。
除了MCFAs C8和C10外，所有其他FFA、MCFAs（C6和C12）以及长链脂肪酸（C14 - C18）在禁食期间均显著增加（P < 0.05）。胃饥饿素酰化作用的倍数变化与循环中的FFA之间没有显著关联。
这些结果表明，循环中MCFAs的变化与禁食期间胃饥饿素酰化作用的下降无关，并支持胃饥饿素的酰化作用至少部分取决于胃腔中MCFAs的可用性或GOAT活性调节的假设。
