Total peptide YY is a correlate of postprandial energy expenditure but not of appetite or energy intake in healthy women

Peptide YY (PYY) and ghrelin have been associated with the regulation of energy balance. The objectives of this study were to determine whether total ghrelin and PYY after a standardized meal predict appetite scores and ad libitum energy intake (EI) and to examine the relationship between total ghrelin and PYY and postprandial energy expenditure (PEE). Twenty-five premenopausal women (age, 50.4 ± 2.0 years; body mass index, 23.5 ± 2.2 kg/m²) were studied. Total PYY, total ghrelin (enzyme-linked immunosorbent assay), EE (indirect calorimetry), and appetite scores (visual analogue scales) were measured fasting and every 30 minute for 3 hours after the ingestion of a standardized breakfast. Ad libitum EI was measured at lunch with a buffet-type meal. Peptide YY increased (P < .001) and total ghrelin decreased (P < .001) after breakfast. Significant changes in EE (P < .001) and appetite scores (P < .001) were noted postprandially. Appetite scores were consistently associated with ad libitum EI at lunch (r = −0.51 to 0.40, P < .05), whereas no association between EI and prelunch total ghrelin and PYY was observed. Finally, partial correlation analyses revealed that total PYY was a significant independent correlate of PEE at 60, 90, 120, and 150 minutes (r = 0.37-0.51, P ≤ .05). These findings provide evidence that appetite scores are better correlates of EI than are circulating levels of total PYY or ghrelin and that total PYY could be involved in the regulation of PEE.     

Plasma acylated ghrelin levels correlate with subjective symptoms of functional dyspepsia in female patients

OBJECTIVE: Ghrelin is a brain-gut peptide that is mainly secreted from gastric endocrine cells (X/A like cells). In addition to promoting growth-hormone release and appetite, ghrelin also affects gastric motility and secretion. Circulating ghrelin levels are related to appetite and energy balance. Functional dyspepsia (FD) is a disorder characterized by the presence of chronic or recurrent symptoms of upper abdominal pain or discomfort. Although no known specific organic abnormalities are present in FD, abnormalities in gastrointestinal motility and sensitivity are thought to play a role in a substantial subgroup of patients. In addition, some patients also suffer from anorexia and body-weight loss. To investigate the role of ghrelin in the pathophysiology of FD, circulating ghrelin levels in affected patients were measured. MATERIAL AND METHODS: Eighteen Japanese female patients with functional dyspepsia and 18 healthy volunteers were recruited for the study. Acylated and desacyl forms of ghrelin were measured using commercially available enzyme-linked immunosorbent assay kits. RESULTS: Although plasma levels of acylated or desacyl ghrelin were not significantly different between healthy subjects and FD patients, plasma acylated, but not desacyl ghrelin, levels were correlated with a subjective symptom score in FD patients. In addition, the ratio of acylated to desacyl ghrelin (A/D ratio) was correlated strongly with acylated, but not desacyl, ghrelin levels. CONCLUSIONS: The correlation of circulating acylated ghrelin levels with the subjective symptom score and the A/D ratio in FD patients suggest that acylated ghrelin may play a role in the pathophysiology of FD.     

Acylated ghrelin level in patients with OSA before and after nasal CPAP treatment

Background and objective: Patients with newly diagnosed OSA have been reported to have recent weight gain prior to diagnosis. Ghrelin stimulates food intake and increases weight gain. Plasma ghrelin is decreased in obese and increased in lean individuals. Of the two circulating forms of ghrelin, acylated and unacylated, the former is thought to be essential for the biological activity of ghrelin. Methods: The plasma levels of the two forms of ghrelin were measured in 21 OSA patients (with a mean of 46.2 sleep‐disordered events/h) before and after 1 month of nasal CPAP (nCPAP) treatment, and were compared with those in 14 untreated OSA patients and 13 individuals without OSA. Results: The BMI was significantly higher in the 21 OSA patients than in the non‐OSA group as were the baseline acylated (11.4 ± 5.86 vs 7.19 ± 3.80 fmol/mL, P = 0.03) and unacylated (84.2 ± 50.6 vs 48.3 ± 23.2 fmol/mL, P = 0.02) ghrelin levels. The total ghrelin level was positively correlated with the number of sleep‐disordered breathings (P = 0.002). After 1 month of nCPAP treatment, the acylated ghrelin level significantly decreased (P = 0.02) while the unacylated ghrelin level did not (P = 0.09). Conclusions: Treatment of OSA may play an important role in the management of obesity in these patients by reducing the acylated ghrelin level.     

ORIGINAL ARTICLE: Dysregulation of plasma ghrelin in alcoholic cirrhosis

Objective Abnormalities in circulating ghrelin have been reported in chronic liver disease. This study assessed the response of anabolic peptides ghrelin, growth hormone (GH) and insulin‐like growth factor 1 (IGF‐1) in patients with alcoholic cirrhosis and healthy subjects to oral glucose. In a previous study, using oral glucose we identified loss of ghrelin regulation in nonalcoholic steato‐hepatitis. Patients/Design/Measurements Fourteen patients with alcoholic cirrhosis were compared with 11 healthy subjects. Patients with cirrhosis were studied when adjudged clinically stable in hospital. After an overnight fast, they ingested 100‐g glucose dissolved in 250 ml of water. Blood was sampled before and every 20 minutes after ingestion for 120 minutes. Plasma acylated and des‐acyl ghrelin, GH, IGF‐1 and insulin were assayed by ELISA. Results Expressed as median (95% CI): 120‐minutes integrated acylated ghrelin was 26 (19–66) in controls compared to 170 (129–252) pg/ml per hour in patients with cirrhosis; P < 0·001. Both groups exhibited a normal postglucose plasma total ghrelin profile. Among patients with cirrhosis (compared to controls), growth hormone was increased 15‐fold and IGF‐1 decreased 4‐fold. Acylated ghrelin correlated with GH (Spearman r = 0·69, P = 0·0015) in control subjects but not in patients with cirrhosis. Conclusions Acylated ghrelin is markedly increased in alcoholic cirrhosis, with apparent preservation of normal postprandial mechanisms of gastric ghrelin secretion. GH is also increased; however, its correlation with acylated ghrelin (confirmed in healthy subjects) is absent in patients with cirrhosis. Despite increased ghrelin and GH, patients with alcoholic cirrhosis remain anorexic and catabolic suggesting potential tissue resistance to the actions of these anabolic peptides.     

Post-prandial decrease of circulating human ghrelin levels.

Ghrelin, an endogenous ligand of the GH secretagogue-receptor, has recently been shown to stimulate GH secretion and to have orexigenic and adipogenic effects in rodents, but little is known about its regulation and biological function in humans. Gastric motor function is under control of the central nervous system; however, the afferent and efferent loops of this feedback control mechanism remain to be elucidated. In the study presented here we investigated the effect of nutrient intake on circulating human ghrelin levels, and a possible association between ghrelin levels and gastric emptying. Ten healthy volunteers received a standard meal after an overnight fast. Food intake significantly decreased plasma ghrelin levels from 248.5 +/- 15.0 to 179.5 +/- 17.9 fmol/ml (120 min after meal, p=0.047). Gastric emptying half-time (non-invasive 13C-octanoic acid breath test) was correlated with fasting plasma ghrelin levels (r=0.74, p=0.0013). Ghrelin appears to be one possible candidate to provide feedback signaling between nutrient intake, gastric motor function and the central nervous system.     

Relation among plasma ghrelin level, gastric emptying, and psychologic condition in patients with functional dyspepsia

BACKGROUND AND GOALS: Neurohormonal factors might play a role in the pathogenesis of functional dyspepsia (FD). However, the role of ghrelin, a gastrointestinal hormone that stimulates gastric motility, in FD is not yet clearly defined. The present study was designed to investigate plasma ghrelin levels and their relation with gastric emptying and psychologic status in FD. METHODS: Sixteen patients with FD of the dysmotility type and 19 healthy controls were enrolled in the study. Plasma active and desacyl ghrelin concentrations before and after test meal were measured by enzyme-linked immunosorbent assay. Gastric emptying and psychologic condition were studied using C acetate breath test and questionnaires, respectively. RESULTS: Gastric emptying was significantly prolonged in patients with FD compared with controls. Fasting desacyl and total ghrelin levels were significantly lower in FD patients than in controls, but fasting active ghrelin levels and postprandial levels of ghrelin in both forms were similar between the 2 groups. Fasting total ghrelin levels in FD patients did not differ from the postprandial levels, in contrast to what was found for controls. There was no significant association among gastric emptying, plasma ghrelin levels, and psychologic factors in FD patients. CONCLUSIONS: Total secretory ability or metabolic condition of ghrelin may be altered in patients with FD. This seems to play a role in the pathophysiology of dysmotility type FD, independent of delayed gastric emptying or psychologic disorders.     

Effect of two fasting periods of different duration on ghrelin response to a mixed meal

Background and aimThe inhibitory effect of food on ghrelin secretion is reduced in several eating disorders such as restricting type anorexia nervosa, bulimia and obesity. These conditions are frequently characterised by irregular distribution of meals during the day. It is unknown whether two short fasting periods different duration affect ghrelin response to a mixed meal. Aim of the present study was to examine, in healthy volunteers, the effects of two fasting periods of different duration on pre- and post-prandial ghrelin concentrations after a standard mixed meal.Methods and resultsNine healthy men (mean age ± S.E.M., 25.1 ± 0.2 years; mean body mass index ± S.E.M., 22.6 ± 0.3 kg/m²) were studied in 2 days after 12 h of fasting (12F) and 17 h of fasting (17F) with a within-subject repeated measure design. On both days they ate a standardized mixed meal. Before each meal hunger rating was evaluated with a visual analogue score. Blood samples for ghrelin, insulin, and glucose were collected at 0, 45, 60, 90, 120, 150 and 180 min after meal.Comparing fasting values of 17F with 12F there was a significant increase in plasma ghrelin (160 ± 20 vs. 146 ± 18 fmol/mL, P = 0.015) and hunger rating (evaluated with a visual analogue scores) (7.0 ± 0.3 vs. 5.1 ± 0.4, P < 0.003). A positive correlation between fasting ghrelin and hunger rating (r = 0.52, P < 0.01) was found. Circulating ghrelin decreased after both meals without any significant difference in relation with the previous length of fasting. Also postmeal ghrelin AUC as well as fasting and postmeal concentrations of insulin and glucose were similar after 12F and 17F.ConclusionsIn healthy subjects a longer fasting period increases ghrelin concentration but did not affect post-prandial ghrelin response to a mixed meal.     

Plasma ghrelin concentrations in different clinical stages of diabetic complications and glycemic control in Japanese diabetics

Ghrelin is an acylated 28-amino-acid peptide that stimulates food intake, GH secretion, and gastric motility. Experimental studies have suggested that ghrelin plays roles in glucose homeostasis, atherosclerosis, and microangiopathy. We investigated possible involvement of ghrelin in micro- and macro-vascular diabetic complications and glycemic control in diabetic patients. Fasting and postprandial plasma ghrelin concentrations after a test meal were measured in 108 and 61 Japanese diabetic patients, respectively. Plasma ghrelin concentrations were negatively correlated with body mass index (BMI) (r = -0.309, P = 0.002) or HbA(1c) (r = -0.264, P = 0.0065). Plasma ghrelin levels in patients with diabetic nephropathy who showed high serum creatinine levels (s-Cre) were significantly higher than those in patients who showed normal s-Cre (P<0.02). In patients with diabetic triopathy, plasma ghrelin concentrations were significantly lower than those in patients without diabetic complications (P<0.05). Stepwise multiple regression analyses revealed that s-Cre, BMI, and HbA(1c) were independently associated with plasma ghrelin levels. A postprandial decrease of ghrelin was observed in patients with normal CV(R-R) values or those with normal body weight, whereas it was not seen in obese patients or in patients with low CV (R-R) values. Suppression rates of ghrelin 30-60 min after a test meal in obese patients were significantly lower than those in normal-weight patients. These findings suggest that ghrelin secretion is suppressed by long-term hyperglycemia and that obesity influences the regulation of ghrelin secretion.     

The role of the small bowel in the regulation of circulating ghrelin levels and food intake in the obese Zucker rat

Circulating levels of ghrelin, a stomach peptide that promotes food intake, rise before and fall after meal. We aimed to investigate whether there is an independent contribution of the small bowel to the regulation of ghrelin and appetite. A duodenal-jejunal bypass (DJB) with preservation of normal gastric volume and exposure to nutrients was performed in 12-wk-old obese Zucker ZDF fa/fa rat. Food intake, weight gain, 48-h fasting, and 24-h refeeding levels of total and acylated ghrelin were measured. The DJB was challenged against gastric banding (GB), diet, and a sham operation in matched animals. Normal controls were age-matched Wistar rats, which underwent either DJB or a sham operation. The Zucker obese animals showed a paradoxical increase of acylated ghrelin levels after refeeding (+30% with respect to fasting levels; P = 0.001), an abnormality that was completely reversed only by the DJB (-30%; P = 0.01) but not after GB, diet, or sham operation. In obese rats, the DJB resulted in significantly less food intake and weight gain compared with both GB (P < 0.05) and sham operation (P < 0.01). In sharp contrast, the DJB did not alter food intake and weight gain in normal rats. The DJB does not physically restrict the flow of food but restores meal-induced suppression of acylated ghrelin and significantly reduces food intake in Zucker obese rats. These findings suggest an independent intestinal contribution to the regulation of the dynamic ghrelin response to eating and the possibility that defective signaling from the proximal bowel could be involved in the pathogenesis of obesity/hyperphagia.     

Fasting plasma total ghrelin concentrations in monozygotic twins discordant for obesity

Ghrelin is a hormone that is involved in the regulation of food intake. Neuronal, endocrine, and genetic factors have been shown to regulate plasma ghrelin levels; but the determinants of fasting ghrelin concentrations are not yet fully understood. The main aim was to explore the roles of adiposity and genetic differences in determining fasting plasma total ghrelin levels. We measured total ghrelin levels in a population of 23 monozygotic twin pairs discordant for obesity. In addition, 2 variants of ghrelin gene, namely, Arg51Gln and Leu72Met, were genotyped in 3 populations of monozygotic twin pairs: 23 obesity-discordant, 43 lean-concordant, and 46 obesity-concordant twin pairs. In discordant twins, lean co-twins had higher fasting plasma total ghrelin levels (950 pg/mL, SD = 328 pg/mL) than obese twins (720 pg/mL, SD = 143 pg/mL; P = .003). Arg51Gln-polymorphism of the ghrelin gene was equally distributed between the twin groups. However, there were significant differences in genotype frequencies at the Leu72Met polymorphism between the discordant and obese-concordant groups (P = .003) and between the discordant and lean-concordant groups (P = .011), but not between the 2 concordant groups. In the discordant group, there were fewer Met carriers (4%) than among the obese (17%) or the lean-concordant groups (15%). Plasma total ghrelin levels are affected by acquired obesity independent of genetic background. The Leu72 allele is particularly common among monozygotic twins discordant for obesity, suggesting that this ghrelin allele is more permissive in the regulation of energy balance. The ghrelin gene may thus play a role in the regulation of variability of body weight, such that Leu72 allele carriers are more prone to weight variability in response to environmental factors.     

The differences in plasma/serum ghrelin levels between obstructive sleep apnea-hypopnea patients and controls: A protocol for systematic review and meta-analysis

Background:The association between obstructive sleep apnea-hypopnea syndrome (OSAHS) and plasma/serum ghrelin levels remains controversial. We performed a meta-analysis to evaluate the difference in plasma/serum ghrelin levels between OSAHS patients and controls.Methods:Database of PubMed, SCI, and Elsevier were searched entirely. Two independents identified eligible studies of ghrelin levels in OSAHS patients. ReviewManager (version 5.3) was adopted for data synthesis.Results:The meta-analysis A pooled the comparison of ghrelin concentrations in OSAHS patients and controls, which included 7 studies and involving 446 participants. The result of the meta-analysis A indicated that plasma/serum ghrelin levels were no significant differences between the OSAHS group and the control group (standard mean difference (SMD) = 0.08, 95% confidence interval (CI) = −0.12 to 0.28, P = .43). As a supplementary, meta-analysis B pooled the comparison of plasma/serum ghrelin levels in OSAHS patients before and after continuous positive airway pressure (CPAP) therapy, which included 155 participants from 4 studies, it revealed that plasma/serum ghrelin levels were no significant differences between before and after CPAP therapy (SMD = 0.12, 95%CI = −0.07 to 0.31, P = .22).Conclusion:The meta-analysis A demonstrated that plasma/serum ghrelin levels were no significant differences between the OSAHS group and the control group. The meta-analysis B showed plasma/serum ghrelin levels have no significant changes after CPAP therapy in OSAHS patients.     

Eradication of Helicobacter pylori increases childhood growth and serum acylated ghrelin levels

AIM: To determine whether Helicobacter pylori (H. pylori)-infected children have reduced body weight (BW) and height (BH) growth, and if H. pylori eradication may restore growth while improving serum acylated ghrelin.METHODS: This longitudinal cohort study with one-year follow-up enrolled 1222 children aged 4 to 12 years old into an observation cohort (18 with and 318 without H. pylori) and intervention cohort (75 with and 811 without). The 7-d triple therapy was used for eradication in the intervention cohort. The net increases of BW and BH as well serum acylated ghrelin after one-year follow-up were compared between successful eradicated H. pylori-infected children and controls.RESULTS: In the observation cohort, the H. pylori-infected children had lower z score of BW (-1.11 ± 0.47 vs 0.35 ± 0.69, P = 0.01) and body mass index (BMI) (0.06 ± 0.45 vs 0.44 ± 0.73, P = 0.02) at enrollment and lower net BW gain after one-year follow-up (3.3 ± 2.1 kg vs 4.5 ± 2.4 kg, P = 0.04) than the non-infected controls. In the intervention cohort, the H. pylori-infected children had lower z score of BMI (0.25 ± 1.09 vs 0.68 ± 0.87, P = 0.009) and serum acylated ghrelin levels (41.8 ± 35.6 pg/mL vs 83.6 ± 24.2 pg/mL, P < 0.001) than the non-infected controls. In addition to restoring decreased serum ghrelin levels (87.7 ± 38.0 pg/mL vs 44.2 ± 39.0 pg/mL, P < 0.001), the H. pylori-infected children with successful eradication had higher net gains (P < 0.05) and increase of z scores (P < 0.05) of both BW and BH as compared with non-infected controls after one-year follow-up.CONCLUSION: H. pylori-infected children are associated with low serum acylated ghrelin and growth retardation. Successful eradication of H. pylori restores ghrelin levels and increases growth in children.     

2型糖尿病患者口服葡萄糖后胆囊收缩素及生长激素释放肽分泌规律分析

目的研究2型糖尿病(T2DM)患者口服葡萄糖后不同时间点血清胆囊收缩素(CCK)及生长激素释放肽(ghrelin)的分泌规律。方法选择T2DM患者82例为T2DM组,纳入同期的健康体检者34例为对照组,收集两组受试者的一般临床资料,检测其空腹和口服葡萄糖后不同时间点血糖、胰岛素、C肽、CCK及ghrelin水平并进行比较。采用Pearson相关分析探讨血清CCK及ghrelin与受试者血糖、胰岛素等因素的相关性。结果T2DM组患者服糖后0、30、60、120和180 min的血糖水平均较对照组高,胰岛素和C肽水平在服糖后30、60和120 min均较对照组低,CCK水平在服糖后60和120 min均较对照组低,ghrelin水平在空腹、服糖后30、60和120 min均较对照组低(P<0.05)。Pearson相关分析结果显示,T2DM患者血清ghrelin水平与BMI水平呈负相关(r=-0.282,P=0.047)。结论T2DM患者口服葡萄糖后CCK及ghrelin分泌较正常人群减少,CCK分泌高峰明显延迟,空腹血清ghrelin与BMI呈负相关。     

Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa.

OBJECTIVE: Ghrelin is a new gastric hormone that has been identified as an endogenous ligand for the growth hormone (GH) secretagogue receptor subtype 1a (GHS-R1a). Ghrelin administration however not only stimulates GH secretion but also induces adiposity in rodents by increasing food intake and decreasing fat utilization. We hypothesized that impaired ghrelin secretion in anorexia nervosa may be involved in the pathogenesis of this eating disorder. To examine this hypothesis and to further investigate the role for ghrelin in regulating energy homeostasis, we analyzed circulating ghrelin levels in patients with anorexia nervosa and examined possible correlations with clinical parameters before and after weight gain. METHODS: Plasma ghrelin levels were measured in overnight fasting plasma samples from 36 female patients with anorexia nervosa (age: 25.0+/-1.2 years, BMI: 15.2+/-0.2 kg/m(2)) before and after weight gain following psychotherapeutic treatment intervention in a psychosomatic institution. Plasma ghrelin levels were also measured in fasting plasma samples from 24 age-matched female controls (31+/-1.4 years, BMI: 22.9+/-0.45 kg/m(2)). For quantification of ghrelin levels a commercially available radioimmunoassay (Phoenix Pharmaceuticals, USA) was used. RESULTS: Fasting plasma ghrelin levels in anorectic patients were significantly higher (1057+/-95 pg/ml) than in normal age-matched female controls (514+/-63 pg/ml n=24, P=0.02). Therapeutic intervention in a psychosomatic institution caused an BMI increase of 14% (P<0.001) leading to a significant decrease in circulating ghrelin levels of 25%, (P=0.001). A significant negative correlation between Deltaghrelin and DeltaBMI was observed (correlation coefficient: -0.47, P=0.005, n=36). CONCLUSION: We show for the first time that fasting plasma levels of the novel appetite-modulating hormone ghrelin are elevated in anorexia nervosa and return to normal levels after partial weight recovery. These observations suggest the possible existence of ghrelin resistance in cachectic states such as caused by eating disorders. Future studies are necessary to investigate putative mechanisms of ghrelin resistance such as a possible impairment of intracellular ghrelin receptor signaling in pathophysiological states presenting with cachexia.     

Loss of meal-induced decrease in plasma ghrelin levels in patients with anorexia nervosa

Studies have shown that ghrelin plays a major role in energy homeostasis and modulation of feeding behavior. However, little is known about the influence of food consumption on plasma ghrelin levels in humans. Therefore, we investigated responses of plasma ghrelin to food intake, meal volume and meal nutritional value in healthy volunteers and women with anorexia nervosa (AN). After overnight fasting, all subjects received either a standardized breakfast or fiber. Plasma ghrelin levels were measured before and after the meal. Fasting plasma ghrelin was significantly higher in AN patients than in controls (1,800.6 +/- 47.0 vs. 795.9 +/- 24.3 pg/ml, P < 0.001) (606.8 +/- 15.8 vs. 268.2 +/- 8.2 pmol/l, P < 0.001), and correlated negatively with percentage of body fat in both groups. Ghrelin levels markedly fell after consumption of either a standardized meal or fiber in controls, but not in anorexic women. Thus, we concluded that the acute plasma ghrelin response to food intake, which in healthy individuals is independent of meal caloric value, is impaired in women with AN. This abnormality may be part of a chronic adaptation to prolonged food restriction, which attempts to restore a normal feeding conduct by maintaining the drive to eat.     

Correlation between gastric myoelectrical activity recorded by multi-channel electrogastrography and gastric emptying in patients with functional dyspepsia

Objective. To investigate the correlation between the parameters of multi-channel electrogastrography (MEGG) and gastric emptying in patients with functional dyspepsia. Material and methods. The MEGG study included 19 patients with functional dyspepsia and 19 healthy subjects. MEGG was recorded for 30?min in the fasting state and 60?min after a standard test meal (450?kcal). MEGG parameters included the power ratio (PR), the normal percentage of 2–4?cpm gastric slow waves (N%) and the percentage of slow wave coupling (%SWC). Gastric emptying was measured in the 19 patients by SPECT (single photon emission computerized tomography) and the gastric emptying parameters included lag phase (LP), half time of gastric emptying (T1/2), emptying rate of stable phase (ERSP), one hour retention rate (1HRR), and two hour retention rate (2HRR). Results. No significant difference in MEGG parameters was found between normal subjects and patients. There was a significant negative correlation between postprandial N% and LP (r=???0.52, p<0.05) and a significant negative correlation between fasting %SWC and 1HRR (r=???0.48, p<0.04) or 2HRR (r=???0.48, p<0.05). Compared with the patients in the PR?>?1 group, patients in the PR?≤?1 group had significantly higher T1/2 and 2HRR but lower ERSP. Conclusions. Both the temporal regularity and spatial regularity of gastric slow waves have negative correlations with gastric emptying, which suggests that the impaired gastric myoelectrical activity may be responsible for the delayed gastric emptying in patients with functional dyspepsia.     

Hyperghrelinemia does not accelerate gastric emptying in Prader-Willi syndrome patients

Prader-Willi syndrome (PWS) is the most common form of syndromic obesity associated with hyperphagia. Because ghrelin stimulates gastric motility in rodents, and PWS patients have 3- to 4-fold higher fasting plasma ghrelin concentrations than normal subjects, we hypothesized that hyperphagia associated with PWS may be partly explained by rapid gastric emptying due to the increased gastric motility caused by ghrelin. We determined gastric emptying times (GETs) and measured ghrelin levels in 11 PWS children and 11 age-, sex-, and body mass index-matched controls using a standard meal containing [(99m)Tc]diaminetriaminepentacetate. Median plasma ghrelin levels before (precibum) and after the GET study were higher in PWS patients than in controls (P = 0.004 and P = 0.001, respectively). Median percent gastric retentions at 90 min after the standard meal were 57.1% (range, 34.0-83.2%) in PWS patients and 40.2% (range, 27.2-60.2%) in controls (P = 0.03). In particular, precibum ghrelin concentrations were not significantly correlated with the rate of gastric emptying in PWS patients (P = 0.153; r = 0.461) or controls (P = 0.911; r = 0.048). Our results show that gastric emptying in PWS is reduced despite higher ghrelin levels, and that the voracious appetite associated with PWS is related to another mechanism.     

Plasma levels of active form of ghrelin during oral glucose tolerance test in patients with anorexia nervosa

OBJECTIVE: Ghrelin is an acylated peptide, whose octanoyl modification is essential for its biological activities. Previous studies demonstrated that fasting plasma ghrelin levels were high in anorectic patients, suggesting ghrelin may play an important role in the pathophysiology of anorexia nervosa. However, antibodies used in previous work to measure ghrelin concentrations in human blood do not distinguish between the active form of ghrelin (active ghrelin) and desacyl ghrelin with no biological activities. Therefore, we studied plasma levels of active ghrelin during oral glucose tolerance test (OGTT) in anorectic patients, using a radioimmunoassay (RIA) specific for active ghrelin. METHODS: Active ghrelin response to OGTT was evaluated in five female anorectic patients and seven age-matched control females. All subjects were given a 75 g/225 ml glucose solution orally after overnight fasting. For RIA of active ghrelin, 1 N hydrogen chloride was added to the samples at final concentration of 0.1 N immediately after separation of plasma. RESULTS: Plasma basal levels of active ghrelin were significantly higher in anorectic patients than in controls (52.1+/-10.5 vs 21.2+/-3.1 fmol/ml, P<0.01). They were significantly decreased during OGTT in anorectic patients and in controls, reaching a nadir of 49.0+/-7.7% and 57.3+/-4.5% of the basal levels, respectively. CONCLUSION: These results suggest that hyperghrelinemia in anorectic patients is caused at least partly by increased secretion of active ghrelin and that glucose ingestion suppresses active ghrelin release in these patients.     

Role of Ghrelin in the Pathophysiology of Gastrointestinal Disease

Ghrelin is a 28-amino-acid peptide that plays multiple roles in humans and other mammals. The functions of ghrelin include food intake regulation, gastrointestinal (GI) motility, and acid secretion by the GI tract. Many GI disorders involving infection, inflammation, and malignancy are also correlated with altered ghrelin production and secretion. Although suppressed ghrelin responses have already been observed in various GI disorders, such as chronic gastritis, Helicobacter pylori infection, irritable bowel syndrome, functional dyspepsia, and cachexia, elevated ghrelin responses have also been reported in celiac disease and inflammatory bowel disease. Moreover, we recently reported that decreased fasting and postprandial ghrelin levels were observed in female patients with functional dyspepsia compared with healthy subjects. These alterations of ghrelin responses were significantly correlated with meal-related symptoms (bloating and early satiation) in female functional dyspepsia patients. We therefore support the notion that abnormal ghrelin responses may play important roles in various GI disorders. Furthermore, human clinical trials and animal studies involving the administration of ghrelin or its receptor agonists have shown promising improvements in gastroparesis, anorexia, and cancer. This review summarizes the impact of ghrelin, its family of peptides, and its receptors on GI diseases and proposes ghrelin modulation as a potential therapy.