Ghrelin and Des-acyl Ghrelin: Two Major Forms of Rat Ghrelin Peptide in Gastrointestinal Tissue

doi:10.1006/bbrc.2000.4039

Biochemical and Biophysical Research Communications

Volume 279, Issue 3, 29 December 2000, Pages 909-913

https://doi.org/10.1006/bbrc.2000.4039 Get rights and content

Abstract

Ghrelin, a novel peptide purified from stomach, is the endogenous ligand for the growth hormone secretagogue receptor and has potent growth hormone-releasing activity. The Ser3 residue of ghrelin is modified by n-octanoic acid, a modification necessary for hormonal activity. We established two ghrelin-specific radioimmunoassays; one recognizes the octanoyl-modified portion and another the C-terminal portion of ghrelin. Using these radioimmunoassay systems, we found that two major molecular forms exist—ghrelin and des-n-octanoyl ghrelin. While ghrelin activates growth-hormone secretagogue (GHS) receptor-expressing cells, the nonmodified des-n-octanyl form of ghrelin, designated as des-acyl ghrelin, does not. In addition to these findings, our radioimmunoassay systems also revealed high concentrations of ghrelin in the stomach and small intestine.

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Acute effects of exercise intensity on butyrylcholinesterase and ghrelin in young men: A randomized controlled study
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Butyrylcholinesterase (BChE), a liver-derived enzyme that hydrolyzes acylated ghrelin to des-acylated ghrelin, may trigger a potential mechanism responsible for the acute exercise-induced suppression of acylated ghrelin. However, studies examining the effects of an acute bout of high-intensity exercise on BChE and acylated ghrelin have yielded inconsistent findings. This study aimed to examine the acute effects of exercise intensity on BChE, acylated ghrelin and des-acylated ghrelin concentrations in humans.
Fifteen young men (aged 22.7 ± 1.8 years, mean ± standard deviation) completed three, half-day laboratory-based trials (i.e., high-intensity exercise, low-intensity exercise and control), in a random order. In the exercise trials, the participants ran for 60 min (from 09:30 to 10:30) at a speed eliciting 70 % (high-intensity) or 40 % (low-intensity) of their maximum oxygen uptake and then rested for 90 min. In the control trial, participants sat on a chair for the entire trial (from 09:30 to 12:00). Venous blood samples were collected at 09:30, 10:00, 10:30, 11:00, 11:30 and 12:00.
The BChE concentration was not altered over time among the three trials. Total acylated and des-acylated ghrelin area under the curve during the first 60 min (i.e., from 0 min to 60 min) of the main trial were lower in the high-intensity exercise trial than in the control (acylated ghrelin, mean difference: 62.6 pg/mL, p < 0.001; des-acylated ghrelin, mean difference: 31.4 pg/mL, p = 0.035) and the low-intensity exercise trial (acylated ghrelin, mean difference: 87.7 pg/mL, p < 0.001; des-acylated ghrelin, mean difference: 43.0 pg/mL, p = 0.042).
The findings suggest that BChE may not be involved in the modulation of ghrelin even though lowered acylated ghrelin concentration was observed after high-intensity exercise.
Desacyl-ghrelin, not just an inactive form of ghrelin? A review of current knowledge on the biological actions of desacyl-ghrelin
2023, Peptides
Desacyl-ghrelin is a form of ghrelin which lacks acyl-modification of the third serine residue of ghrelin. Originally, desacyl-ghrelin was considered to be just an inactive form of ghrelin. More recently, however, it has been suggested to have various biological activities, including control of food intake, growth hormone, glucose metabolism, and gastric movement, and is involved in cell survival. In this review, we summarize the current knowledge of the biological actions of desacyl-ghrelin and the proposed mechanisms by which it exerts the effects.
Sarcopenic obesity in free-living older adults detected by the ESPEN-EASO consensus diagnostic algorithm: Validation in an Italian cohort and predictive value of insulin resistance and altered plasma ghrelin profile
2023, Metabolism: Clinical and Experimental
Aging and obesity are synergistic sarcopenia risk factors (RF). Their association in sarcopenic obesity (SO) enhances morbidity and mortality, but consensus on SO diagnostic criteria is limited. ESPEN and EASO issued a consensus algorithm for SO screening (obesity and clinical SO suspicion) and diagnosis [low muscle strength by hand-grip (HGS) and low muscle mass by BIA], and we investigated its implementation in older adults (>65-years), as well as SO-associated metabolic RF [insulin resistance (IR: HOMA) and plasma acylated (AG) and unacylated (UnAG) ghrelin, with predictive value also assessed from 5-year-prior observations]. Older adults with obesity from the Italian MoMa study on metabolic syndrome in primary care (n = 76) were studied. 7 of 61 individuals with positive screening had SO (SO+; 9 % of cohort). No individuals with negative screening had SO. SO+ had higher IR, AG and plasma AG/UnAG ratio (p < 0.05 vs negative screening and SO-), and both IR and ghrelin profile predicted 5-year SO risk independent of age, sex and BMI. The current results provide the first ESPEN-EASO algorithm-based investigation of SO in free-living older adults, with 9 % prevalence in those with obesity and 100 % algorithm sensitivity, and they support IR and plasma ghrelin profile as SO risk factors in this setting.
First insights about orexigenic activity and gastrointestinal tissue localization of ghrelin from Corvina drum (Cilus gilberti)
2023, Aquaculture
The croaker Cilus gilberti commonly known as Corvina drum is considered a target marine species for the diversification of Chilean aquaculture. To optimize culture conditions, molecular markers for appetite regulation must be examined. Ghrelin, a gastrointestinal peptide, plays a stimulatory role in the food intake of mammals and teleost fish. Nevertheless, even though the appetite-controlling system is considered relatively well conserved among vertebrates, the bioactivity of these molecules should be analyzed in each fish species. Therefore, this study aimed to investigate the expression and orexigenic ability of C. gilberti ghrelin. After the pre and postprandial period, the stomach expression of ghrelin mRNA in juvenile C. gilberti was analyzed. The coding sequence of C. gilberti ghrelin was used to identify the mature peptide and then chemically synthesized. The orexigenic ability of acylated ghrelin (cgGhre) and non-acylated (D-cgGhre) ghrelin was tested in C. gilberti juveniles. Moreover, the blood and the gastrointestinal location of synthetic ghrelin after intraperitoneal injection were measured. The results showed that the stomach has the highest expression of ghrelin mRNA, and that ghrelin levels increased in the preprandial period and diminished after it. There were no differences in the secondary structure of D-cgGhre compared to cgGhre but the peptide with the serine acylation stabilized its unordered conformation. However, the highest cumulative feed intake occurred in fish intraperitoneally injected with cgGhre. In addition, synthetic ghrelin was maintained in the C. gilberti blood until 8 h post-injection (hpi). Finally, biotinylated ghrelin allowed localizing the synthetic peptide in digestive tissue, mainly in the stomach and pyloric caeca. The mRNA expression of the growth hormone secretagogue receptor (GHS-R), also known as the ghrelin receptor, in gastrointestinal organs supports the idea of peripheral orexigenic regulation in these tissues. In conclusion, results suggest that C. gilberti ghrelin conserves the orexigenic ability reported in other teleost fish with a regulatory role in the gastrointestinal tract (GIT) of the Corvina drum. This is the first report demonstrating the uptake and distribution of a small orexigenic peptide in the digestive tissues of a South American sciaenid. Although ghrelin is a promising molecular marker for feed intake analysis in C. gilberti culture, further research is needed to continue evaluating the effects of aquaculture practices on peripheral appetite signalizer.
Down regulation of the hippocampal ghrelin receptor type-1a during electrical kindling-induced epileptogenesis
2023, Epilepsy Research
Numerous studies have shown that the ghrelin hormone is involved in epileptic conditions. However, the profile of ghrelin or its functional receptor mRNAs in seizure-susceptible brain areas was not assessed during epileptogenesis. Here, we measured the expression levels of the hippocampal ghrelin or its receptor mRNAs during electrical kindling-induced epileptogenesis. The study was conducted on twenty adult male Wistar rats. One tri-polar and two uni-polar electrodes were stereotaxically implanted in the baso-lateral amygdala or skull surface, respectively. Animals were divided into four groups, consisting of two sham groups (sham1 and sham2), and two other groups, which were partially or fully kindled. After the establishment of partial or full kindling, the hippocampi of the animals and that of the corresponding sham groups were removed. A quantitative real-time PCR technique was used to measure the expression levels of ghrelin or its functional receptor mRNAs. The results indicated that the expression levels of ghrelin did not alter in either of the partially or fully kindled rats compared to the corresponding sham groups. Ghrelin receptor (ghrelinR) down regulated, significantly in the fully-kindled rats, compared to sham2 group. Meanwhile, the mRNA expression levels of ghrelinR did not change in partially-kindled rats compared to sham1 group. The outcomes of the current study highlight the crucial, unknown impact of the hippocampal ghrelinR through the development of electrical kindling epileptogenesis, and points out the importance of ghrelinR as a goal to adjust epileptogenic progression.
Involvement of ghrelin in the regulation of swallowing motor activity in an arterially perfused rat preparation
2023, Brain Research Bulletin
Ghrelin, a peripheral peptide produced in the stomach, is involved in the neural networks that control food intake. Alterations in motor components, such as swallowing, are believed to be significant in the regulation food intake by orexigenic signals. However, there has been no detailed investigation of the relationship between ghrelin and swallowing activities induced in motor nerves innervating the pharyngeal and laryngeal muscles. In this study, we examined the effects of ghrelin administration on swallowing motor activity in arterially perfused rats. Injection of distilled water (0.5 ml) into the oral cavity or electrical stimulation of the superior laryngeal nerve evoked swallowing motor activity in the cervical vagus nerve. Administration of ghrelin (6 nM), but not des-acylated ghrelin (6 nM), into the perfusate increased the peak burst amplitude and burst duration, and shortened the first burst interval of water injection-induced swallowing. These ghrelin-induced changes in swallowing motor activity were blocked by the administration of JMV2959 (6 µM), a growth hormone secretagogue receptor antagonist. In preparations in which the hypothalamus was removed, ghrelin had no effect on swallowing motor activity. Furthermore, ghrelin-induced changes were counteracted by the administration of BIBO3304 (1 µM) or L-152,804 (1 µM), antagonists of neuropeptide Y Y1 and Y5 receptors, respectively, which are essential for ghrelin-induced enhancement of food intake. Ghrelin also increased the peak burst amplitude and burst duration of the swallowing motor activity evoked by electrical stimulation of the superior laryngeal nerve, although the effects of ghrelin on the number of swallowing bursts and burst intervals varied with stimulus intensity. These results suggest that ghrelin enhances the magnitude and frequency of bursts of swallowing motor activity by acting via the hypothalamic neural network, and that neuropeptide Y Y1 and Y5 receptors are involved in this enhancement.

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Regular ArticleGhrelin and Des-acyl Ghrelin: Two Major Forms of Rat Ghrelin Peptide in Gastrointestinal Tissue

Abstract

Genomics

Brain Res. Mol. Brain Res.

FEBS Lett.

Biochem. Biophys. Res. Commun.

Regular Article
Ghrelin and Des-acyl Ghrelin: Two Major Forms of Rat Ghrelin Peptide in Gastrointestinal Tissue