Plasma Des-acyl Ghrelin Levels Research Articles

Administration of a standard dose of vonoprazan fumarate delays gastric emptying in Japanese healthy adults: a prospective clinical trial.

There is no established view of how gastric acid suppression affects the time for gastric emptying. Vonoprazan fumarate shows potent and durable gastric acid inhibitory effects, but its effects on gastric emptying have not been studied widely. We investigated the effects of vonoprazan fumarate on gastric emptying and measured serum gastrin and plasma ghrelin levels in healthy adults. Ten participants were administered 10mg vonoprazan fumarate daily for 14days, then 20mg vonoprazan fumarate daily for 14days. The gastric emptying breath test was performed and serum gastrin levels were measured at baseline and after each medication administration period. The protocol was then repeated, with the gastric emptying breath test and serum gastrin and plasma desacyl-ghrelin levels measured at baseline and the end of the medication trial. Mean serum gastrin levels increased in a dose-dependent manner [baseline: 104.7 ± 50.4, after 10mg protocol: 328 ± 123.8, after 20mg protocol: 555 ± 378.8 (pg/mL, mean ± standard deviation), p = 0.0008]. There was a significant difference between the gastric emptying breath test Tmax at baseline and just after the 20mg protocol (baseline: 45.5 ± 15.3, after 20mg protocol: 60.5 ± 19.6min, p = 0.0418). Plasma desacyl-ghrelin levels increased significantly just after the 20mg protocol compared to those at baseline [baseline: 222.3 ± 106.4, after 20mg protocol: 366.2 ± 178.6 (fmol/mL), p = 0.0008]. In healthy adults, 14days of vonoprazan fumarate administration at 20mg/day delayed gastric emptying. This clinical trial was registered in the University hospital Medical Information Network Clinical Trial Registry (Trial No. UMIN000039199 and UMIN000042969).

MON-603 GPR142 Expression Levels Were Correlated with Plasma Ghrelin Levels and Heights in Morbidly Obese Patients

Recently, aromatic amino acids, especially tryptophan were discovered to be the strongest ligands for GPR142, which was previously known as an orphan GPCR. GPR142 is expressed in the digestive tract and pancreas in mice and human. Previously we found that GPR142 is highly expressed in the ghrelin-producing cell line, MGN3-1 cells, and that tryptophan strongly stimulated ghrelin secretion in vitro.In this study, we measured the mRNA expression levels of GPR142 in the gastric samples of 6 morbid obese patients undergone laparoscopic sleeve gastrectomy and compared its level with their clinical parameters. GPR142 expression levels were negatively correlated with plasma desacyl ghrelin levels (p=0.011) and positively correlated with heights (p=0.08).The current results that GPR142 expression levels were correlated with plasma desacyl ghrelin levels may confirm the link between GPR142 signal and regulation of ghrelin secretion demonstrated in our in vitro study. Regarding to the correlation with heights, there are some reports that plasma ghrelin levels were inversely correlated with heights in children[1-3], although, as far as we know, there are no reports demonstrating the relationship between plasma ghrelin levels and heights in adults. Considering that ghrelin strongly stimulates growth hormone secretion, GPR142 signaling may have influence on height through regulating ghrelin-growth hormone axis.ConclusionGPR142 mRNA expression levels were negatively and positively correlated with plasma desacyl ghrelin levels and heights in morbid obese adults undergone bariatric surgery. Current results may help understanding the pathophysiological role of GPR142 in the regulation of ghrelin secretion and heights.

Association of baseline plasma des-acyl ghrelin level with the response to rikkunshito in patients with functional dyspepsia.

We recently conducted a randomized placebo-controlled trial on the efficacy and safety of rikkunshito, a standardized Japanese herbal medicine, for the treatment of functional dyspepsia (FD). The present post-hoc study aimed to evaluate the differences in clinical characteristics between responders and non-responders among FD patients who received rikkunshito for 8 weeks. Rikkunshito responders were defined by using a global patient assessment. Candidate predictors included age, gender, smoking, alcohol consumption, body mass index, comorbidity, Helicobacter pylori infection, plasma levels of acyl ghrelin and des-acyl ghrelin, severity of dyspeptic symptoms, FD subgroup, previous medication, and the type of recruiting institution (clinic or hospital). We calculated hazard ratios (HRs) by using Cox regression analysis with the factors that were indicated to be associated with responders. We assigned 83 and 42 patients to responder and non-responder categories, respectively. Lack of alcohol consumption (HR, 2.04; 95% confidence interval, 1.08-3.88) and low plasma des-acyl ghrelin levels (< 177 fmol/mL; HR, 2.42; 95% confidence interval, 1.24-4.73) were significantly associated with the efficacy of rikkunshito. Lack of alcohol consumption was associated with the efficacy of rikkunshito especially among H. pylori-infected participants. On the other hand, the low plasma des-acyl ghrelin was associated with the efficacy of rikkunshito especially among H. pylori-negative participants. A low baseline level of plasma des-acyl ghrelin was associated with an increased treatment efficacy of rikkunshito against FD. Lack of alcohol consumption was also clinically useful for predicting the response to rikkunshito.

Comparison of gut hormones and adipokines stimulated by glucagon test among patients with type II diabetes mellitus after metabolic surgery

Laparoscopic Roux-en-Y gastric bypass (RYGB) achieves a higher remission of type 2 diabetes mellitus (T2DM) than laparoscopic sleeve gastrectomy (SG) in non-morbidly obese patients. However, the mechanisms of the higher remission are unknown. To compare glucagon-provoked acute insulin responses, as well as changes of gut and pancreatic hormones and adipokines between patients with T2DM after RYGB and SG at one year post-operatively, a total of 14 RYGB and 13 SG patients were followed-up and evaluated for glucose metabolism, gut and pancreatic hormones, and adipokines. One year after surgery, 1-mg intravenous glucagon tests were performed. The differences in each hormone at different time points and the area under the curve (AUC) were compared between the two groups. Glucagon-stimulated acute insulin responses were not different between the RYGB and SG groups, nor were they different between the remitters and non-remitters at one year after the metabolic surgery. Plasma des-acyl ghrelin and nesfatin-1 levels significantly decreased at 6min after glucagon stimulation in the RYGB and SG groups, as well as in the remitters and non-remitters. The glucagon test did not affect intestinal hormones. Plasma resistin was suppressed after intravenous glucagon stimulation in both RYGB and SG groups. In conclusion, intravenous glucagon inhibited plasma levels of des-acyl ghrelin, nesfatin-1, and resistin in T2DM patients at one year after both RYGB and SG, whereas post-glucagon suppression of plasma obestatin and resistin was shown in the remitters but not in the non-remitters.

Administration of exogenous acylated ghrelin or rikkunshito, an endogenous ghrelin enhancer, improves the decrease in postprandial gastric motility in an acute restraint stress mouse model

BackgroundPhysical or psychological stress causes functional disorders in the upper gastrointestinal tract. This study aims to elucidate the ameliorating effect of exogenous acylated ghrelin or rikkunshito, a Kampo medicine which acts as a ghrelin enhancer, on gastric dysfunction during acute restraint stress in mice.MethodsFasted and postprandial motor function of the gastric antrum was wirelessly measured using a strain gauge force transducer and solid gastric emptying was detected in mice exposed to restraint stress. Plasma corticosterone and ghrelin levels were also measured. To clarify the role of ghrelin on gastrointestinal dysfunction in mice exposed to stress, exogenous acylated ghrelin or rikkunshito was administered, then the mice were subjected to restraint stress.Key ResultsMice exposed to restraint stress for 60 min exhibited delayed gastric emptying and increased plasma corticosterone levels. Gastric motility was decreased in mice exposed to restraint stress in both fasting and postprandial states. Restraint stress did not cause any change in plasma acylated ghrelin levels, but it significantly increased the plasma des-acyl ghrelin levels. Administration of acylated ghrelin or rikkunshito improved the restraint stress-induced delayed gastric emptying and decreased antral motility. Ameliorating effects of rikkunshito on stress-induced gastric dysfunction were abolished by simultaneous administration of a ghrelin receptor antagonist.Conclusions & InferencesPlasma acylated/des-acyl ghrelin imbalance was observed in acute restraint stress. Supplementation of exogenous acylated ghrelin or enhancement of endogenous ghrelin signaling may be useful in the treatment of decreased gastric function caused by stress.

Association of Plasma Des-acyl Ghrelin Levels with CKD

There are no effective therapies for malnutrition in CKD/ESRD patients. This study hypothesized that ghrelin, an endogenous orexigenic hormone, would correlate with renal function and might suggest therapeutic interventions for CKD/ESRD malnutrition. Fifty-one CKD and 15 hemodialysis patients were enrolled. Acyl ghrelin (AG) and des-acyl ghrelin (DG) were determined using separate two-site-specific assays. Leptin, insulin, growth hormone, insulin-link growth factor-1, C-reactive protein, TNF-α, and IL-6 were also measured. Univariate correlation analyses showed that CKD stage was highly, positively correlated with the levels of preprandial and postprandial DG and positively correlated with TNF-α, IL-6, leptin, and age. Multivariate partial-correlation analyses showed that CKD was independently associated with the proportion of preprandial and postprandial DG, whereas TNF-α, IL-6, leptin, insulin, and age were not independently associated with either. Geometric mean (GM) preprandial and postprandial AG were comparable between CKD stages ≤2 and >2, whereas GM preprandial DG and postprandial DG were 1.95-fold and 2.17-fold greater, respectively, for CKD stage >2 versus stage ≤2. DG was the dominant form of ghrelin preprandially and postprandially for both CKD stages ≤2 and >2. Dialysis had no effect on AG, but reduced DG by 73% to levels even lower (GM 48.7 pg/ml) than those seen postprandially in CKD stage ≤2 patients (GM 77.0 pg/ml). This study shows a strong and independent correlation of DG with CKD stage. Postprandial suppression of ghrelin is impaired with reduced renal function. Hemodialysis selectively removes DG but not AG.

Plasma ghrelin isoforms and gastric ghrelin O-acyltransferase expression are influenced by Helicobacter pylori status

ObjectiveHelicobacter pylori is known to affect the host’s nutritional status. This study was performed to elucidate the relationship between H. pylori status and the dynamics of the ghrelin system, in the context of ghrelin O-acyltransferase (GOAT) expression. MethodsWe conducted a clinical study of 30 subjects focusing on the following points: 1) the effects of H. pylori infection on the concentrations of circulating ghrelin isoforms and on ghrelin and GOAT mRNA expression in the gastric mucosa, and 2) the effects of H. pylori eradication on the same parameters. ResultsThe plasma acyl-ghrelin and desacyl-ghrelin concentrations of 16 H. pylori positive participants were significantly lower than those of 14 H. pylori negative controls. The acyl-ghrelin/desacyl-ghrelin ratio was not significantly different between the H. pylori positive and H. pylori negative participants. The levels of ghrelin and GOAT mRNA in the gastric mucosa were significantly lower in the H. pylori positive participants than in the H. pylori negative controls. In 11 subjects in whom H. pylori eradication was successful, their plasma acyl-ghrelin levels tended to increase after H. pylori eradication, but the difference was not significant; however, their plasma desacyl-ghrelin levels were significantly reduced. Although gastric ghrelin mRNA expression increased significantly after H. pylori eradication, gastric GOAT mRNA expression tended to increase but was not significantly altered. ConclusionH. pylori status might affect the host’s nutritional status through changes in the plasma levels of ghrelin isoforms and the gastric expression levels of ghrelin and GOAT mRNA.

Changes of ghrelin and leptin levels in plasma by cigarette smoke in rats

Cigarettes smoke (CS) limits food intake and body weight increase. Ghrelin and leptin are hormones regulating appetite and energy balance. While ghrelin increases food intake and causes a positive energy balance, leptin decreases food intake and enhances a negative energy balance. To investigate the possible role of ghrelin and leptin regarding the negative energy balance caused by CS, 10-week old male Wistar rats (n = 10) were exposed to CS from 30 cigarettes twice a day for 5 days a week for four weeks. In the smoking group, food intake and body weight gain were less than those in the non-smoking group (n = 10) during the entire CS exposure. In the smoking group, the plasma levels of acyl ghrelin were significantly higher (75.9 ± 5.1 fmol/ml versus 46.5 ± 3.3 fmol/ml, p < 0.01), while those of leptin were significantly lower than those in the non-smoking group (434.9 ± 41.1 ng/ml versus 744.0 ± 45.4 ng/ml, p < 0.01) after the final CS exposure. However, the plasma des-acyl ghrelin levels were not affected by CS exposure. These results suggested that acyl ghrelin and leptin levels in plasma may change to compensate for the negative energy balance by CS.

Significant lowering of plasma ghrelin but not des-acyl ghrelin in response to acute exercise in men

Ghrelin, an acylated peptide produced predominantly in the stomach, stimulates feeding and growth hormone (GH) secretion via interaction with the GH secretagogue receptor. Ghrelin molecules are present in two major endogenous forms, an acylated form (ghrelin) and a des-acylated form (des-acyl ghrelin). Recent studies indicated that aerobic exercise did not change plasma total ghrelin levels, however, dynamics of circulating ghrelin and des-acyl ghrelin during aerobic exercise remains unclear. The purpose of this study is to examine the effects of moderate intensity exercise on plasma ghrelin and des-acyl ghrelin concentrations, and to investigate the relationship between ghrelin molecules and other hormonal and metabolic parameters during exercise. Nine healthy males (25.2 ± 0.5 years) exercised for 60 min at 50% of their maximal oxygen consumptions. We measured the plasma concentrations of ghrelin, des-acyl ghrelin, GH, norepinephrine (NE), epinephrine (E), dopamine (DA), insulin, and glucose. Plasma ghrelin level significantly decreased during exercise, whereas plasma des-acyl ghrelin and total ghrelin levels did not change. Plasma NE, E, DA and GH levels were significantly increased during exercise. Plasma insulin level significantly decreased during exercise, and plasma glucose levels remained steady during exercise. NE, E, DA, and GH were correlated negatively with plasma ghrelin levels. These findings suggest that acute moderate exercise may suppress ghrelin release from the stomach, decrease ghrelin O-acyltransferase activity, and/or activate ghrelin utilization in peripheral tissues and that exercise-induced ghrelin suppression may be mediated by activated adrenergic system.

Acylated and des acyl ghrelin in human portal and systemic circulations

Octanoylation of the gastric peptide ghrelin produces an active isoform that regulates appetite and other metabolic functions. Acylated ghrelin is present in the gastrointestinal tract suggesting that octanoylation may occur in these tissues and thereby affect the acylated ghrelin in the systemic circulation. In this study blood samples were collected simultaneously from portal, arterial, peripheral venous and central venous compartments from patients undergoing laparotomy. ELISA and high sensitivity Bioplex was used to measure the concentration of acylated and des acyl ghrelin. We found median (95% confidence interval (CI)) plasma acylated ghrelin (pg/ml) was 35.8 (30.0-59.6) in the portal compartment compared to 51.5 (37.6-74.8; P < 0.05, n = 11) in the arterial, 39.3 (33.3-56.3) in the portal compartment compared to 55.0 (48.5-77.0; P < 0.001, n = 12) in the peripheral venous and 36.0 (33.1-57.4) in the portal compartment compared to 48.9 (43.3-65.6; P < 0.01, n = 15) in the central venous compartment. Median (95% CI) plasma des acyl ghrelin levels (pg/ml) was 173 (125-220) in the portal compartment compared to 136 (99.3-125; P < 0.001, n = 14)in the arterial, 186 (136-233) in the portal compartment compared to 149 (111-190; P < 0.01, n = 15) in the peripheral venous and 171 (140-208) in the portal compartment compared to 152 (119-175; P < 0.01, n = 15) the central venous compartment. We conclude that plasma acylated ghrelin concentration was significantly lower in portal compared with the systemic compartments whilst plasma des acyl ghrelin was significantly higher in portal compared with systemic compartments. These findings suggest that the liver could be involved in the regulation of circulating ghrelin.

Effect of octanoic acid-rich formula on plasma ghrelin levels in cachectic patients with chronic respiratory disease

BackgroundFor cachectic patients with chronic respiratory disease (CRD), conventional enteral nutrition formula is an optional treatment to maintain energy balance. The molecular mechanisms by which enteral nutrition formula controls appetite and weight remain unknown. We examined whether enteral nutrition formula rich in octanoic acids would increase plasma levels of ghrelin, an appetite-stimulating hormone produced in the stomach, in cachectic patients with CRD.MethodsPlasma ghrelin profiles in cachectic patients with CRD were assessed and compared with those in age- and sex-matched controls. Plasma levels of acyl-ghrelin, an active ghrelin modified by octanoic acids, and desacyl-ghrelin were measured separately. We examined changes in 24-h plasma ghrelin profiles before and after single administration of the formula. We also evaluated the effects of 2-week administration of the formula on plasma ghrelin levels and nutritional status in patients.ResultsThe ratio of acyl-ghrelin to desacyl-ghrelin in plasma was lower in patients than in controls. Single administration of the formula did not change plasma desacyl-ghrelin levels, but induced an increase in acyl-ghrelin levels. Two-week treatment with the formula was effective in increasing weight and acyl-ghrelin, along with improving nutritional status in patients.ConclusionThese results show that the formula contributes to increased weight, which may be associated with induction of acyl-ghrelin production in cachectic patients with CRD.

Dose-Dependent Effects of Barley Cooked with White Rice on Postprandial Glucose and Desacyl Ghrelin Levels

White rice is an indispensable staple food in Japan, although it is a high glycemic index food. The objective of this study was to estimate how barley cooked with white rice might affect postprandial glucose, insulin and desacyl ghrelin concentrations as well as fullness. The study was conducted in randomized crossover design with nine healthy subjects. Blood glucose, insulin, free fatty acid and desacyl ghrelin concentrations and subjective levels of fullness and hunger were measured for 240 min after intake of glucose, white rice, 30% rolled barley (30BAR), 50% rolled barley (50BAR) and 100% rolled barley (100BAR) containing 75 g of available carbohydrate. Postprandial glucose and insulin levels were suppressed by intake of 30BAR, 50BAR and 100BAR comparing with those of white rice. Area under the curves of plasma glucose and insulin concentrations was reduced by barley intake in a dose-dependent manner. Although plasma desacyl ghrelin levels decreased postprandially, the degree of reduction was suppressed by barley intake in a dose-dependent manner. Postprandial desacyl ghrelin levels can be a sensitive biomarker of carbohydrate metabolism. The combination of white rice with barley plays a beneficial role in preventing and treating type 2 diabetes, obesity and other metabolic diseases.

No Relationship between Plasma Desacyl-Ghrelin Levels and Rabeprazole-Related Delay in Gastric Emptying

Recent studies have indicated that rabeprazole, a proton pump inhibitor, delays gastric emptying. However, the mechanism of action remains unclear. We conducted this study to clarify whether desacyl-ghrelin (the inactive form of the endogenous growth hormone secretagogue receptor ghrelin) is involved in rabeprazole-induced changes in gastric motor function. Twelve healthy males underwent (13)C-acetate breath tests to evaluate gastric emptying of a liquid meal twice after administration of rabeprazole 20 mg/day for 3 days or no medication (control). Gastric emptying was evaluated by two parameters: half-emptying time and time to peak (13)CO(2) excretion. Plasma desacyl-ghrelin levels were measured in blood samples collected at three time points: immediately pre-test and 1 and 2 hours after ingestion of the test meal. Rabeprazole significantly delayed gastric emptying of the liquid meal. However, plasma desacyl-ghrelin levels after ingestion of the liquid meal showed little difference before or after rabeprazole administration. The results indicate that desacyl-ghrelin was not associated with changes in gastric emptying caused by rabeprazole.

Anorexia in Hemodialysis Patients: The Possible Role of Des-Acyl Ghrelin

Background: Anorexia is frequently found in end-stage renal disease and is a reliable predictor of morbidity and mortality in hemodialysis (HD) patients. The pathogenesis of anorexia is complex and the appetite-modulating hormone ghrelin could be involved. Two forms of circulating ghrelin have been described: acylated ghrelin (<10% of circulating ghrelin) which promotes food intake, and des-acyl ghrelin which induces a negative energy balance. The aim of this cross-sectional study is to clarify whether anorexia and body weight change in HD patients relate to plasma des-acyl ghrelin levels. Methods: 34 HD patients and 15 healthy controls were studied. The presence of anorexia was assessed by a questionnaire. Serum des-acyl ghrelin was measured in HD patients and in 15 body mass index-, sex- and age-matched controls by ELISA. Energy intake was assessed by a 3-day dietary diary, and fat-free mass (FFM) was evaluated by body impedance analysis. Data have been statistically analyzed and are presented as mean ± SD. Results: 14 patients (41%) were found to be anorexic, and 20 patients (59%) non-anorexic. Energy intake (kcal/day) was significantly lower in anorexic than in non-anorexic patients (1,682 ± 241 vs. 1,972.50 ± 490; p < 0.05). FFM (%) was lower in anorexic than in non-anorexic patients (65.8 ± 4.4 vs. 70.9 ± 8.7; p = 0.05). Plasma des-acyl ghrelin levels (fmol/ml) were significantly higher in HD patients than in controls (214.88 ± 154.24 vs. 128.93 ± 51.07; p < 0.05), and in anorexic HD patients than in non-anorexic (301.7 ± 162.4 vs. 159.1 ± 115.5; p < 0.01). Conclusion: Anorexia is highly prevalent among HD patients and des-acyl ghrelin could be involved in its pathogenesis.

Hyperphagia Alters Expression of Hypothalamic 5-HT2C and 5-HT1B Receptor Genes and Plasma Des-Acyl Ghrelin Levels in AyMice

The central melanocortin (MC) pathway is suggested to mediate satiety signaling downstream of serotonin (5-HT)2C receptors. 5-HT2C receptor mutant mice consume more food, which leads to late-onset obesity and impaired glucose tolerance. Ay mice with ectopic expression of the agouti peptide, which leads to a perturbation of the central MC pathway, develop obesity and diabetes, associated with low levels of plasma total ghrelin. Here, we report that 5-wk-old Ay mice consumed more food in association with decreases in levels of plasma des-acyl ghrelin, but not active ghrelin, and increases in hypothalamic 5-HT2C and 5-HT1B receptor gene expression compared with wild-type mice matched for age and body weight. These alterations were also observed in 8-wk-old obese Ay mice. Restricted feeding significantly decreased hypothalamic 5-HT2C and 5-HT1B receptor gene expression in association with a reversal of the decreases in plasma des-acyl ghrelin levels in 5-wk-old Ay mice. Moreover, restricted feeding reduced body weight, hyperinsulinemia, and hyperglycemia in association with increases in plasma des-acyl ghrelin levels in 8-wk-old obese Ay mice. Administration of m-chlorophenylpiperazine and fenfluramine, both of which induce anorexic effects via 5-HT2C receptors and/or 5-HT1B receptors, suppressed food intake in 5- and 8-wk-old Ay mice, whereas the anorexic effects were attenuated in food-restricted Ay mice. These findings suggest that the agouti peptide down-regulates hypothalamic 5-HT2C and 5-HT1B receptor gene expression under restricted feeding conditions, whereas chronic hyperphagia increases the expression of these genes and decreases plasma des-acyl ghrelin levels in Ay mice.

Induction of hypothalamic serum- and glucocorticoid-induced protein kinase-1 gene expression and its relation to plasma des-acyl ghrelin in energy homeostasis in mice

Serum- and glucocorticoid-induced protein kinase (SGK) is a serine/threonine-specific protein kinase that is transcriptionally regulated by serum, glucocorticoids, and mineral corticoids. Here, we report that fasting or obesity with hyperphagia increased hypothalamic SGK-1 gene expression. Hypothalamic SGK-1 mRNA levels were proportional to daily food intake and body weights in C57BL6J mice, KK mice, and KKA y mice matched for age. Plasma des-acyl ghrelin, but not active ghrelin, levels were inversely proportional to daily food intake and body weights among these animals. The increases in hypothalamic SGK-1 gene expression in these animals were not accompanied by increases in plasma corticosterone levels. Under conditions of increased energy usage such as fasting, hypothalamic SGK-1 gene expression and plasma des-acyl ghrelin levels were positively correlated while during conditions of increased energy storage, they were negatively correlated. These results suggest that hypothalamic SGK-1 gene is a novel candidate gene involving in energy homeostasis in mice.

Transgenic mice overexpressing des-acyl ghrelin show small phenotype.

Ghrelin, a 28-amino acid acylated peptide, displays strong GH-releasing activity in concert with GHRH. The fatty acid modification of ghrelin is essential for the actions, and des-acyl ghrelin, which lacks the modification, has been assumed to be devoid of biological effects. Some recent reports, however, indicate that des-acyl ghrelin has effects on cell proliferation and survival. In the present study, we generated two lines of transgenic mice bearing the preproghrelin gene under the control of chicken beta-actin promoter. Transgenic mice overexpressed des-acyl ghrelin in a wide variety of tissues, and plasma des-acyl ghrelin levels reached 10- and 44-fold of those in control mice. They exhibited lower body weights and shorter nose-to-anus lengths, compared with control mice. The serum GH levels tended to be lower, and the serum IGF-I levels were significantly lower in both male and female transgenic mice than control mice. The responses of GH to administered GHRH were normal, whereas those to administered ghrelin were reduced, especially in female transgenic mice, compared with control mice. These data suggest that overexpressed des-acyl ghrelin may modulate the GH-IGF-I axis and result in small phenotype in transgenic mice.