Plasma Acylated Ghrelin Levels Research Articles

Association of Pro-Ghrelin Leu72Met Polymorphism with Acylated Ghrelin Level and Alcohol Use Disorder: A Preliminary Study

Objective: Multiple environmental and genetic factors contribute to the progression of alcohol use disorder (AUD). Ghrelin is one of the important elements of the brain-gut axis that has been believed to involve in the pathophysiology of addiction. This study aimed to determine whether the GHRL Leu72Met gene polymorphism has an effect on the plasma acylated ghrelin levels in alcohol addicts for the first time.
 Method: A sample of 50 alcohol-dependent men and 50 controls were enrolled in this study. Acylated ghrelin levels were detected by ELISA kit. The GHRL Leu72Met polymorphism was analyzed by the standard PCR-RFLP method. 
 Results: Acylated ghrelin levels were significantly higher in AUD patients than in controls, and were lower in AUD patients with Leu72Leu than those with Leu72Met and Met72Met. After detoxification, a dramatic decrease was seen in AUD patients having Leu72Met+Met72Met. The presence of 72Met allele was also found to be associated with an increased risk of AUD in Turkish men.
 Conclusion: It was indicated for the first time that the GHRL Leu72Met variant was associated with higher plasma acylated levels in patients with AUD. The GHRL Leu72 allele compared to the Met72 allele seemed to be protective against AUD in Turkish men. Taken together, despite the small number of subjects evaluated, the findings in this study suggested the effect of the GHRL Leu72Met polymorphism on plasma acylated ghrelin levels and alcohol addiction.

Decreased plasma ghrelin in male ALS patients is associated with poor prognosis

Physiological changes including altered nutritional status influence disease progression and survival in patients with amyotrophic lateral sclerosis (ALS). Ghrelin affects the nutritional status by regulating appetite and energy expenditure, and also has neuroprotective effects. To investigate the association between ghrelin and ALS prognosis, we analyzed plasma acylated-ghrelin levels in 33 patients with ALS. Compared among ALS patients, male had lower plasma ghrelin levels than female, although disease specificity is unknown. ALS patients, especially male ALS patients, with low plasma ghrelin levels (<15 fmol/mL) had significantly shorter post-examination survival times than those with high plasma ghrelin levels (≥15 fmol/mL). Univariate and multivariate analyses revealed a significant effect of ghrelin levels on post-examination survival. Immunohistochemical study of autopsied stomach samples from 8 of 33 patients revealed that the population of ghrelin-positive cells tended to be reduced in the low-plasma ghrelin group than in the high-plasma ghrelin group. Our findings suggest that ghrelin levels are an independent predictor of survival in ALS, especially male ALS patients, and the ghrelin-positive cells may decrease in ALS with low plasma ghrelin. Thus, reduced ghrelin secretion may be associated with poor prognosis among patients with ALS.

Assessments of plasma acyl-ghrelin levels and body weight in advanced Parkinson's disease after subthalamic nucleus deep brain stimulation

Objective: The effect of STN DBS on ghrelin concentration and consequently on motility disturbances as well as body weight in advanced PD is unclear. The objective of this study was to assess acyl-ghrelin levels in comparison to weight in advanced PD patients treated with STN DBS.

Assessments of plasma acyl-ghrelin levels in Parkinson’s disease patients treated with deep brain stimulation

Gastrointestinal dysfunction is the most common non-motor symptom in Parkinson’s disease (PD) with rates rising as the disease progresses. Deep brain stimulation of subthalamic nucleus (STN DBS) improves motor functions in advanced PD. However, the effect of STN DBS on ghrelin concentration and consequently on motility disturbances as well as body weight is unclear. The objective of this study was to assess acyl-ghrelin levels in comparison to weight in advanced PD patients treated with STN DBS.Plasma concentrations of acyl-ghrelin was measured in 29 PD patients in the fasting state and at 30, 60, 120, and 180 min after a standard meal preoperatively and 3 months after surgery. The level of acyl-ghrelin in PD patients were compared with 30 age and sex-matched healthy controls.We reported that mean plasma acyl-ghrelin levels were decreased in PD patients before STN DBS in fasting (p = 0.0003) and in 30 min postprandial phase (p = 0.04) compared with healthy controls. The plasma acyl-ghrelin levels after STN DBS increased in pre-prandial and postprandial phase in PD patients at the investigated time points. Body weight gained on average 2.33 kg during the first 3 months after surgery. There was no correlation between the acyl-ghrelin plasma levels and BMI.After STN DBS in fasting and postprandial phase plasma acyl-ghrelin levels were increased. The results showed that STN DBS therapy elicited a modification of ghrelin levels, increasing its concentration in pre- and postprandial state. In addition, body weight was increased during 3 months after surgery.

Estradiol Replacement Improves High-Fat Diet-Induced Obesity by Suppressing the Action of Ghrelin in Ovariectomized Rats.

This study aims to investigate the effects of estradiol replacement on the orexigenic action of ghrelin in ovariectomized (OVX) obese rats fed with a high-fat diet (HFD). Four weeks after OVX at 9 weeks of age, Wistar rats were subcutaneously implanted with either 17β-estradiol (E2) or placebo (Pla) pellets and started on HFD feeding. After 4 weeks, growth hormone-releasing peptide (GHRP)-6, a growth hormone secretagogue receptor (GHSR) agonist injected intraperitoneally, induced changes in HFD intake, and c-Fos-positive neurons in the hypothalamic arcuate nucleus (ARC) were measured in both groups. The ghrelin protein and mRNA levels, as well as GHSR protein in stomach, were analyzed by Western blotting and real-time PCR. HFD increased energy intake and body weight in the Pla group, while it temporarily reduced these in the E2 group. GHRP-6 enhanced HFD intake and activated neurons in the ARC only in the Pla group. Furthermore, gastric ghrelin and GHSR protein levels were lower in the E2 group than in the Pla group, but plasma acyl ghrelin levels were similar in both groups. Our results suggest that E2 replacement improves obesity by inhibiting the orexigenic action of ghrelin via downregulation of ghrelin and its receptor in stomach in HFD-fed OVX rats.

Prospective, randomized, cross-over pilot study of the effects of Rikkunshito, a Japanese traditional herbal medicine, on anorexia and plasma-acylated ghrelin levels in lung cancer patients undergoing cisplatin-based chemotherapy.

Purpose Anorexia induced by cytotoxic chemotherapy on delayed phase is a highly frequent adverse event. We aimed to determine the effects of rikkunshito (RKT) on chemotherapy-induced anorexia (CIA) in patients with lung cancer. Methods This prospective, randomized, cross-over pilot trial included 40 lung cancer patients scheduled to undergo cisplatin-based chemotherapy and randomized to either a group given RKT 7.5g/day for 14days (Group A, N = 20) or not (Group B, N = 20), then the treatments were switched. All patients received dexamethasone, palonosetron hydrochloride and aprepitant regardless of group assignment. Rescue drugs were allowed as required. The primary and key secondary endpoints were changes in caloric intake and in plasma acylated ghrelin (AG) levels, respectively. Average daily caloric intake during days 3 to 5 was compared with that on day 1 of each course. Results The primary and key secondary endpoints were analyzed in 31 patients (per protocol population) completing the study. Reduction rate of caloric intake was lower in RKT, than in control courses (18% vs. 25%, P = 0.025). Plasma AG levels significantly declined between days 1 and 3 in RKT (12.3 vs. 7.5 fmol/mL, P < 0.001) and control (10.8 vs. 8.6 fmol/mL, P < 0.001) courses. However, those obviously increased to 8.5 fmol/mL (P = 0.025) by day 5 in RKT course but not in control course (7.7 fmol/mL, P = 0.28). Conclusions Rikkunshito could mitigate CIA and ameliorate plasma AG levels during the delayed phase of CDDP-based chemotherapy in lung cancer patients. Clinical trial registration numbers: UMIN000010748.

Traditional Japanese herbal medicine rikkunshito increases food intake and plasma acylated ghrelin levels in patients with esophageal cancer treated by cisplatin-based chemotherapy

Cisplatin (CDDP) is an important chemotherapeutic drug for treating esophageal cancer that often induces nausea and vomiting. Rikkunshito (RKT), a traditional Japanese herbal medicine, can increase levels of plasma ghrelin, which is an orexigenic gut hormone that can alleviate chemotherapy-induced nausea and vomiting (CINV) and anorexia. This prospective randomized crossover study included 20 patients with esophageal cancer who were administered with CDDP-based chemotherapy. Ten of them were assigned to group A [1st course: with RKT 7.5 g/day on days 1-14; 2nd course: without RKT (control)] and 10 were assigned to group B [1st course: without RKT (control); 2nd course: with RKT 7.5 g/day on days 22-35]. Food intake and levels of plasma acylated ghrelin (AG) were compared between the control and RKT courses. Data from 18 patients were included in this analysis, as chemotherapy was immediately stopped due to deteriorating renal function in one patient and intracerebral bleeding in another. The median rate at which food intake decreased between days 4 and 6 was considerably lower in the course with, than without RKT (2% vs. 30%; P=0.02). Median levels of AG significantly increased from days 3 to 8 in patients in both courses with and without RKT (9.6 to 15.7 fmol/mL, P<0.0001; control, 10.2 to 17.8, P=0.0002). The rate at which median plasma AG levels increased from days 3 to 8 tend to be higher in the RKT, than in the control course (68% vs. 48%, P=0.08). RKT can improve CDDP-induced, delayed-onset anorexia and increase plasma AG levels among patients with esophageal cancer who undergo highly emetogenic chemotherapy (HEC).

Postoperative decrease in plasma acyl ghrelin levels after pediatric living donor liver transplantation in association with hepatic damage due to ischemia and reperfusion injury.

Ghrelin was recently reported to promote recovery from hepatic injury. We hypothesized that it could also be associated with clinical recovery of the transplanted liver from ischemia and reperfusion injury. Our aims were to investigate perioperative ghrelin changes following pediatric living donor liver transplantation (LDLT) and to analyze the association of these changes with postoperative hepatic function. We measured plasma acyl ghrelin (AG) concentrations before surgery, at the end of surgery and on postoperative days (PODs) 1, 3 and 7 in 12 children who underwent LDLTs, and, as controls, pre- and post-operatively and on POD1 in 7 children who underwent benign abdominal mass resection. The correlations between the participants' ghrelin profiles and hepatic function-related data were evaluated. AG levels significantly declined to 15.6% of preoperative levels after LDLT and almost returned to baseline on POD3. Post-operative AG levels were significantly reduced to a greater extent following LDLT than benign abdominal mass resection. AG levels on POD1 inversely correlated with aspartate aminotransferase levels and cold/total ischemia time (P < 0.05). These results suggest that reduced AG levels on POD1 may reflect the degree of damage to the transplanted liver due to ischemia and reperfusion injury.

Total and acylated ghrelin plasma levels as potential long-term response markers in alcohol-dependent patients receiving high-dose of the GABA-B receptor agonist baclofen

The orexigenic hormone ghrelin is involved in the regulation of food intake and energy balance. Previous findings suggest its involvement in the modulation of mesolimbic reward pathways, thus potentially being relevant in the pathophysiology of substance use disorders such as alcohol dependence. In the present study, we assessed plasma levels of total and acylated ghrelin within the BACLAD trial, where alcohol-dependent patients received individually titrated high-dose baclofen (30–270 mg/d) within a randomized, placebo-controlled design. Plasma levels of total ghrelin and acylated ghrelin were measured at baseline, during treatment with individually titrated high-dose baclofen and after termination of the study medication within a timeframe of up to 20 weeks. Multivariate longitudinal non-parametric analysis revealed that plasma levels of total ghrelin significantly decreased in the group of abstinent patients receiving high-dose baclofen. In addition, plasma levels of total ghrelin correlated negatively with days of abstinence during treatment with high-dose baclofen. Plasma levels of acylated ghrelin increased during the study in the group of relapsed patients under baclofen and placebo treatment. These findings suggest that the long-term response to baclofen treatment in alcohol use disorder (AUD) might be monitored by assessing total and acylated ghrelin plasma levels.

Gender Differences in Plasma Ghrelin Levels in Hemodialysis Patients.

Ghrelin is an orexigenic hormone mainly secreted by the stomach, and it decreases according to the severity of gastric atrophy. Ghrelin has multiple favorable functions, including protein anabolism enhancement, anti-inflammatory activity, and cardiovascular protection, and is associated with survival in hemodialysis (HD) patients. Although the plasma level and role of ghrelin may be different depending on gender, they have not been completely assessed in HD patients. We enrolled 80 (male/female: 51/29) maintenance HD patients. An upper gastrointestinal endoscopic examination was performed for all patients to determine the severity of gastric mucosal atrophy and Helicobacter pylori infection. We measured plasma acyl and desacyl ghrelin levels and assessed the association between ghrelin levels and relevant clinical parameters, including nutrition, inflammation, atherosclerosis, and bone metabolism, by gender. Both acyl and desacyl ghrelin levels in female HD patients were significantly higher than those in male HD patients. When stratified by gastric mucosal atrophy, these gender differences were observed only in patients without gastric atrophy. In female patients, acyl ghrelin level was negatively correlated with age. In male patients, both acyl and desacyl ghrelin levels were positively correlated with bone mineral density. Multiple regression analysis showed significant positive correlations between both ghrelin levels and female gender after adjusting for confounding factors. Plasma ghrelin levels were higher in female HD patients than in male HD patients. The gender difference was more evident in patients without gastric atrophy.

\u03b2-Oxidation in ghrelin-producing cells is important for ghrelin acyl-modification

Ghrelin is a unique fatty acid-modified peptide hormone produced in the stomach and has important roles in energy homeostasis and gastrointestinal motility. However, the medium-chain fatty acid source for ghrelin acyl-modification is not known. We found that a fat-free diet and the removal of intestinal microbiota did not decrease acyl-ghrelin production in the stomach or plasma acyl-ghrelin levels in mice. RT-PCR analysis showed that genes involving fatty acid synthesis, metabolism, and transport were expressed in pancreas-derived ghrelinoma (PG-1) cells. Treatment with an irreversible inhibitor of carnitine palmitoyltransferase-1 (CPT-1) strongly decreased acylated ghrelin levels but did not affect ghrelin or ghrelin o-acyl transferase (GOAT) mRNA levels in PG-1 cells. Our results suggest that the medium-chain fatty acid used for the acyl-modification of ghrelin is produced in ghrelin-producing cells themselves by β-oxidation of long-chain fatty acids provided from the circulation.

Prospective randomized crossover study of effects of traditional Japanese herbal medicine rikkunshito on food intake and plasma acylated ghrelin levels in patients with esophageal cancer administered with cisplatin-based chemotherapy.

133 Background: Cisplatin (CDDP) is an important chemotherapeutic drug for treating esophageal cancer that often induces chemotherapy-induced nausea and vomiting (CINV). Acylated ghrelin (AG) is an orexigenic gut hormone that can alleviate CINV. We evaluated whether rikkunshito (RKT), a traditional Japanese herbal medicine with an orexigenic effect, can improve CINV-induced anorexia and increase levels of plasma AG in patients with esophageal cancer administered with CDDP-based chemotherapy. Methods: This prospective randomized crossover study included 20 patients with esophageal cancer who were administered with CDDP-based chemotherapy between July 2013 and March 2016. Tenof them were assigned to group A (1st course with 7.5 g/day RKT on days 1 - 14; 2nd course without RKT [control]) and 10 were assigned to group B (1st course without RKT [control]; 2nd course with RKT). Food intake and levels of plasma AG (fmol/mL) were compared between the control and RKT courses. Results: Data from 18 of the patients were included in this analysis, as chemotherapy was immediately stopped due to deteriorating renal function in one patients and intracerebral bleeding in another. The median rate at which food intake decreased between days 4 and 6, which is associated with delayed-onset CINV, was considerably lower in the groups given RKT than in the control (2% vs. 30%; p = 0.07). Median levels of AG significantly decreased between days 1 to 3 in the group given RKT (15.1 to 9.6 fmol/mL, p = 0.001) and the control (14.1 to 10.2, p = 0.003), and then obviously increased from days 3 to 8 in patients with both courses (RKT: 9.6 to 15.7 fmol/mL, p &lt; 0.0001; control: 10.2 to 17.8, p = 0.0002). However, the rate at which median plasm AG levels increased from days 3 to 8 tend to be higher in the RKT, than in the control group (68% vs. 48%, p = 0.08). Conclusions: RKT might improve delayed-onset CINV as well as CINV-induced anorexia and increases in plasma AG levels among patients with esophageal cancer who undergo highly emetogenic CDDP-based chemotherapy. Clinical trial information: UMIN000010747.

Open Label Trial of the Efficacy and Safety Profile of Rikkunshito used for the Treatment of Gastrointestinal Symptoms in Patients with Parkinson’s Disease: A Pilot Study

BackgroundPatients with Parkinson’s disease (PD) usually experience distress related not only to motor dysfunction, but also to nonmotor symptoms, including gastrointestinal dysfunction. ObjectiveThe purpose of this pilot study was to evaluate the efficacy and safety profile of a traditional Japanese medicine, rikkunshito (RKT), used for the treatment of gastrointestinal symptoms, associated with anorexia and dyspepsia, in patients with PD. MethodsPatients were randomly assigned to either Group A (4-week treatment period with 7.5 g/d RKT followed by a 4-week off-treatment period) or Group B (4-week off-treatment period followed by a 4-week treatment period with 7.5 g/d RKT). Appetite, quality of life for gastrointestinal symptoms, and depression were assessed using a visual analog scale, the Gastrointestinal Symptom Rating Scale and the Self-Rating Depression Scale, respectively. The gastric emptying examination and assay of plasma acylated ghrelin level were performed using the 13C-acetate breath test and commercially available assay kits, respectively. ResultsRKT treatment produced a significant increase in the appetite score (1.84 [2.34]; P < 0.05), compared to a decrease in the score over the off-treatment period (−1.36 [2.94]). The mean score for abdominal pain, on the Gastrointestinal Symptom Rating Scale, and for self-reported depression, on the Self-Rating Depression Scale, also decreased significantly with RKT treatment (P < 0.05), compared with the off-treatment period scores. No effect of RKT on plasma acylated ghrelin level and rate of gastric emptying was identified. ConclusionsRKT may improve anorexia in patients with PD. The positive effects of RKT on depression and anorexia may improve the overall quality of life of these patients. The benefits of RKT identified in our pilot study will need to be confirmed in a randomized, double-blind, controlled trial. UMIN Clinical Trial Registry identifier: UMIN000009626.

Intermittent access to a nutritionally complete high-fat diet attenuates alcohol drinking in rats

Binge eating disorder and alcohol use disorder (AUD) frequently co-occur in the presence of other psychiatric conditions. Data suggest that binge eating engages similar behavioral and neurochemical processes common to AUD, which might contribute to the etiology or maintenance of alcoholism. However, it is unclear how binge feeding behavior and alcohol intake interact to promote initiation or maintenance of AUD. We investigated the impact of binge-like feeding on alcohol intake and anxiety-like behavior in male Long Evans rats. Rats received chow (controls) or extended intermittent access (24h twice a week; Int-HFD) to a nutritionally complete high-fat diet for six weeks. Standard rodent chow was available ad-libitum to all groups and food intake was measured. Following HFD exposure, 20.0% ethanol, 2.0% sucrose intake and endocrine peptide levels were evaluated. Anxiety-like behavior was measured using a light-dark (LD) box apparatus. Rats in the Int-HFD group displayed a binge-like pattern of feeding (alternations between caloric overconsumption and voluntary caloric restriction). Surprisingly, alcohol intake was significantly attenuated in the Int-HFD group whereas sugar consumption was unaffected. Plasma acyl-ghrelin levels were significantly elevated in the Int-HFD group, whereas glucagon-like peptide-1 levels did not change. Moreover, rats in the Int-HFD group spent more time in the light side of the LD box compared to controls, indicating that binge-like feeding induced anxiolytic effects. Collectively, these data suggest that intermittent access to HFD attenuates alcohol intake through reducing anxiety-like behavior, a process potentially controlled by elevated plasma ghrelin levels.

1473P - The effect of rikkunshito, a traditional Japanese herbal medicine, on food intake and plasma acylated ghrelin levels in lung cancer patients treated with platinum-based chemotherapy

1473P - The effect of rikkunshito, a traditional Japanese herbal medicine, on food intake and plasma acylated ghrelin levels in lung cancer patients treated with platinum-based chemotherapy

Severity of Gastric Mucosal Atrophy Is the Major Determinant of Plasma Ghrelin Level in Hemodialysis Patients

Background: Ghrelin, an orexigenic hormone, has multiple favorable functions including protein anabolism enhancement, anti-inflammatory actions, and cardiovascular protection. A low plasma ghrelin level is associated with increased mortality in patients treated with hemodialysis (HD). However, it is unclear whether the plasma ghrelin level in HD patients correlates with the severity of gastric mucosal atrophy and Helicobacter pylori status. Methods: Seventy-eight maintenance HD patients and 51 non-dialysis patients with chronic kidney disease were evaluated for severity of gastric mucosal atrophy by gastroduodenoscopy and for H. pylori status using an anti-H. pylori-antibody and rapid urease test. Plasma acyl and des-acyl ghrelin levels were measured and their associations with relevant clinical parameters were investigated. Results: Des-acyl ghrelin level in HD patients was significantly higher than that in patients with kidney function preserved. Although acyl and des-acyl ghrelin levels were similar between current H. pylori positive and negative HD patients, both levels decreased significantly with the progress of endoscopic gastric mucosal atrophy in HD patients. Serum pepsinogen (PG) I level and PG I/II ratio decreased significantly according to the severity of atrophy in HD patients and positively significantly correlated with both ghrelin levels. Multiple regression analysis showed significant positive correlations between acyl ghrelin and PG I levels (β = 0.738, p < 0.001) and significant negative correlations between ghrelin and age, albumin, and creatinine levels. Conclusions: Gastric atrophy is the major determinant of ghrelin level in HD patients. Management practices, such as H. pylori eradication, before advanced atrophy may be required to prevent the decrease of ghrelin levels and improve the prognosis of HD patients.

Jejunal administration of glucose enhances acyl ghrelin suppression in obese humans.

Ghrelin is a gastric hormone that stimulates hunger and worsens glucose metabolism. Circulating ghrelin is decreased after Roux-en-Y gastric bypass (RYGB) surgery; however, the mechanism(s) underlying this change is unknown. We tested the hypothesis that jejunal nutrient exposure plays a significant role in ghrelin suppression after RYGB. Feeding tubes were placed in the stomach or jejunum in 13 obese subjects to simulate pre-RYGB or post-RYGB glucose exposure to the gastrointestinal (GI) tract, respectively, without the confounding effects of caloric restriction, weight loss, and surgical stress. On separate study days, the plasma glucose curves obtained with either gastric or jejunal administration of glucose were replicated with intravenous (iv) infusions of glucose. These "isoglycemic clamps" enabled us to determine the contribution of the GI tract and postabsorptive plasma glucose to acyl ghrelin suppression. Plasma acyl ghrelin levels were suppressed to a greater degree with jejunal glucose administration compared with gastric glucose administration (P < 0.05). Jejunal administration of glucose also resulted in a greater suppression of acyl ghrelin than the corresponding isoglycemic glucose infusion (P ≤ 0.01). However, gastric and isoglycemic iv glucose infusions resulted in similar degrees of acyl ghrelin suppression (P > 0.05). Direct exposure of the proximal jejunum to glucose increases acyl ghrelin suppression independent of circulating glucose levels. The enhanced suppression of acyl ghrelin after RYGB may be due to a nutrient-initiated signal in the jejunum that regulates ghrelin secretion.

The effects of rikkunshito on body weight loss after esophagectomy

BackgroundAfter esophagectomy, esophageal cancer patients suffer from malnutrition, anorexia, and dysfunction of digestion and absorption. Rikkunshito, a traditional Japanese herbal medicine, reportedly attenuates gastrointestinal symptoms and appetite loss after gastrointestinal surgery. We evaluated the clinical effect of rikkunshito and its relationship with ghrelin in esophageal cancer patients after esophagectomy. MethodsThis prospective nonrandomized study included 40 patients with esophageal cancer who underwent esophagectomy at Wakayama Medical University Hospital. They were assigned to either the control group (n = 20, April 2011-January 2012) or the rikkunshito group (n = 20, January 2012-August 2012). Patients in the rikkunshito group received 2.5 g of rikkunshito before every meal for 48 wk beginning 4 wk after surgery. During the 48-week treatment, we assessed body weight loss, nutritional parameters, and quality of life (Functional Assessment of Cancer Therapy-Esophageal scale). The primary end point was the rate of body weight loss in two groups after the 48-week treatments. ResultsThe rate of body weight loss was significantly less in the rikkunshito group than in the control group (P = 0.016). The acyl ghrelin level after the 48-week treatments was significantly higher in the rikkunshito group (131.7% ± 74.5%) than in the control group (75.6% ± 47.5%, P = 0.039). For the Functional Assessment of Cancer Therapy-Esophageal symptom scale, satisfaction of food consumption in the rikkunshito group was significantly better than in the control group at 52 wk postoperatively (P = 0.031). ConclusionsFor esophageal cancer patients after esophagectomy, rikkunshito is useful for improving body weight loss in connection with an increase in plasma acyl ghrelin levels.

Influence of Aging and Gender Differences on Feeding Behavior and Ghrelin-Related Factors during Social Isolation in Mice.

Psychological stress due to social isolation is known to cause abnormal feeding behaviors, but the influences of gender and aging on subchronic stress-induced changes in feeding behaviors are unknown. Thus, we examined the changes in body weight, food intake, and orexigenic ghrelin-related factors during 2 weeks of isolation stress in young and aged mice. Food intake increased significantly in young mice in the isolation group compared with the group-housed control throughout the experimental period. This isolation-induced increase in food intake was not observed in aged mice. In young mice, there were no significant differences in body weight between the isolated group and group-housed control up to 2 weeks. However, aged male mice exhibited significant weight loss at 2 weeks and a similar tendency was observed in aged female mice. Young male mice, but not female mice, had significantly increased (2.2-fold) plasma acylated ghrelin levels after 1 week of isolation compared with the group-housed control. A significant but lower increase (1.3-fold) was also observed in aged male mice. Hypothalamic preproghrelin gene expression decreased significantly with isolation in young male mice, whereas it increased significantly in female mice. The expression levels of NPY and AGRP in the hypothalamus, which are transmitted by elevated peripheral ghrelin signals, increased significantly in isolated young male mice, whereas the AGRP expression levels decreased significantly in young female mice. Isolation caused no significant differences in the expression levels of these genes in aged mice. In isolation, young female mice exhibited markedly increased dark- and light-phase locomotor activities compared with male mice, whereas male and female aged mice exhibited no obvious increases in activity immediately after the dark phase started. We conclude that the gender-specific homeostatic regulatory mechanisms required to maintain body weight operated during subchronic psychological stress in young mice but not in aged mice.

Increase in plasma acyl ghrelin levels is associated with abatement of dyspepsia following Helicobacter pylori eradication.

Ghrelin has been indicated as one of the etiological factors in functional dyspepsia (FD). We analyzed 179 patients with FD (based on the Rome III criteria) and 103 asymptomatic healthy individuals (controls) who had undergone endoscopy at Seoul National University Bundang Hospital from February 2011 to June 2014. FD patients were classified into three groups by means of a self-reported questionnaire: patients with postprandial distress syndrome (PDS; n=49), patients with epigastric pain syndrome (EPS; n=45), and patients with a combination of these two types (mixed group; n=85). The fasting blood levels of acyl ghrelin and desacyl ghrelin and messenger RNA (mRNA) expression of preproghrelin in the fundic mucosa were measured by ELISAs and reverse transcription quantitative real-time PCR, respectively. One year after participant enrollment, they were measured again in 79 participants and the changes in the values were compared according to Helicobacter pylori eradication or symptom response. Plasma acyl ghrelin level was lower in the PDS group than in the control and EPS groups (control group 14.1 fmol/mL, PDS group 8.9 fmol/mL, EPS group 13.8 fmol/mL, mixed group 11.3 fmol/mL; P=0.003 and P=0.012, respectively). One year after the eradication of H.pylori, plasma acyl ghrelin level was increased and gastric preproghrelin mRNA expression was upregulated (P=0.004 and P<0.001, respectively). Patients with abatement of symptoms demonstrated an increase in plasma acyl ghrelin level (from 11.51 to 21.00fmol/L, P=0.040). Our results suggest that plasma acyl ghrelin plays a role in the development of PDS. H.pylori eradication upregulates preproghrelin mRNA expression and increases plasma acyl ghrelin level, contributing to the abatement of PDS symptoms.