Plasma Acyl Ghrelin Research Articles

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.

β1-adrenergic receptors mediate plasma acyl-ghrelin elevation and depressive-like behavior induced by chronic psychosocial stress.

The ghrelin system is a key component of the mood and metabolic responses to chronic psychosocial stress. For example, circulating acyl-ghrelin rises in several rodent and human stress models, administered acyl-ghrelin induces antidepressant-like behavioral responses in mice, and mice with deleted ghrelin receptors (GHSRs) exhibit exaggerated depressive-like behaviors, changed eating behaviors, and altered metabolism in response to chronic stress. However, the mechanisms mediating stress-induced rises in ghrelin are unknown and ghrelin's antidepressant-like efficacy in the setting of chronic stress is incompletely characterized. Here, we used a pharmacological approach in combination with a 10-day chronic social defeat stress (CSDS) model in male mice to investigate whether the sympathoadrenal system is involved in the ghrelin response to stress. We also examined the antidepressant-like efficacy of administered ghrelin and the synthetic GHSR agonist GHRP-2 during and/or after CSDS. We found that administration of the β1-adrenergic receptor (β1AR) blocker atenolol during CSDS blunts the elevation of plasma acyl-ghrelin and exaggerates depressive-like behavior. Neither acute injection of acyl-ghrelin directly following CSDS nor its chronic administration during or after CSDS nor chronic delivery of GHRP-2 during and after CSDS improved stress-induced depressive-like behavior. Thus, β1ARs drive the acyl-ghrelin response to CSDS, but supplementing the natural increases in acyl-ghrelin with exogenous acyl-ghrelin or GHSR agonist does not further enhance the antidepressant-like actions of the endogenous ghrelin system in the setting of CSDS.

Appetite Perceptions, Gastrointestinal Symptoms, Ghrelin, Peptide YY and State Anxiety Are Disturbed in Adolescent Females with Anorexia Nervosa and Only Partially Restored with Short-Term Refeeding.

Factors underlying disturbed appetite perception in anorexia nervosa (AN) are poorly characterized. We examined in patients with AN whether fasting and postprandial appetite perceptions, gastrointestinal (GI) hormones, GI symptoms and state anxiety (i) differed from healthy controls (HCs) and (ii) were modified by two weeks of refeeding. 22 female adolescent inpatients with restricting AN, studied on hospital admission once medically stable (Wk0), and after one (Wk1) and two (Wk2) weeks of high-calorie refeeding, were compared with 17 age-matched HCs. After a 4 h fast, appetite perceptions, GI symptoms, state anxiety, and plasma acyl-ghrelin, cholecystokinin (CCK), peptide tyrosine tyrosine (PYY) and pancreatic polypeptide (PP) concentrations were assessed at baseline and in response to a mixed-nutrient test-meal (479 kcal). Compared with HCs, in patients with AN at Wk0, baseline ghrelin, PYY, fullness, bloating and anxiety were higher, and hunger less, and in response to the meal, ghrelin, bloating and anxiety were greater, and hunger less (all p < 0.05). After two weeks of refeeding, there was no change in baseline or postprandial ghrelin or bloating, or postprandial anxiety, but baseline PYY, fullness and anxiety decreased, and baseline and postprandial hunger increased (p < 0.05). We conclude that in AN, refeeding for 2 weeks was associated with improvements in PYY, appetite and baseline anxiety, while increased ghrelin, bloating and postprandial anxiety persisted.

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.

Eradication therapy for Helicobacter pylori infection improves nutrition status in Japanese hemodialysis patients: a pilot study.

Plasma ghrelin level is influenced by Helicobacter pylori (H. pylori) status and the severity of gastric mucosal atrophy, and the ghrelin level is associated with nutrition status in hemodialysis patients. Here, we investigated the efficacy of H. pylori eradication therapy in improving nutrition status in relation to the ghrelin level in H. pylori-positive hemodialysis patients. Of H. pylori-positive patients receiving hemodialysis at 8 dialysis center, 21 patients underwent gastroduodenoscopy for evaluation of the severity of gastric atrophy, and nutrition markers and plasma ghrelin levels before and 1 year after H. pylori eradication therapy were evaluated. Serum cholinesterase level was significantly increased after H. pylori eradication compared with the level before eradication (303.2 ± 76.0 vs 287.3 ± 68.1 IU/L, p = 0.029). In particular, cholesterol (before, 196.6 ± 23.2 mg/dl; after, 206.1 ± 25.9 mg/dl, p = 0.042) and cholinesterase levels (before, 296.9 ± 70.8 IU/L; after, 316.4 ± 73.8 IU/L, p = 0.049) increased more strongly in patients with mild–moderate atrophy than those with severe atrophy, irrespective of improvement of plasma acyl-ghrelin and desacyl-ghrelin levels after eradication therapy. In conclusion, H. pylori eradication may improve nutrition status by increasing serum cholinesterase and cholesterol levels in hemodialysis patients, especially those with mild and moderate gastric mucosal 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.

Ghrelin mediates exercise endurance and the feeding response post-exercise

ObjectiveExercise training has several well-established health benefits, including many related to body weight, appetite control, and blood glucose homeostasis. However, the molecular mechanisms and, in particular, the hormonal systems that mediate and integrate these beneficial effects are poorly understood. In the current study, we aimed to investigate the role of the hormone ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR; ghrelin receptor), in mediating the effects of exercise on food intake and blood glucose following exercise as well as in regulating exercise endurance capacity. MethodsWe used two mouse models of treadmill running to characterize the changes in plasma ghrelin with exercise. We also assessed the role of the ghrelin system to influence food intake and blood glucose after exercise, exercise endurance, and parameters potentially linked to responses to exercise. Mice lacking GHSRs (GHSR-null mice) and wild-type littermates were studied. ResultsAn acute bout of exercise transiently elevated plasma acyl-ghrelin. Without the action of this increased ghrelin on GHSRs (as in GHSR-null mice), high intensity interval exercise markedly reduced food intake compared to control mice. The effect of exercise to acutely raise blood glucose remained unmodified in GHSR-null mice. Exercise-induced increases in plasma ghrelin positively correlated with endurance capacity, and time to exhaustion was reduced in GHSR-null mice as compared to wild-type littermates. In an effort to mechanistically explain their reduced exercise endurance, exercised GHSR-null mice exhibited an abrogated sympathoadrenal response, lower overall insulin-like growth factor-1 levels, and altered glycogen utilization. ConclusionsExercise transiently increases plasma ghrelin. GHSR-null mice exhibit decreased food intake following high intensity interval exercise and decreased endurance when submitted to an exercise endurance protocol. These data suggest that an intact ghrelin system limits the capacity of exercise to restrict food intake following exercise, although it enhances exercise endurance.

Ghrelin concentration as an indicator of eating-disorder risk in obese women

AimEating disorders (EDs), disordered eating (DE) and obesity are thought to have overlapping aetiological processes. DE in obesity can jeopardize weight-loss results, and acyl ghrelin (AG) is a hormone that stimulates food intake and reward processes. The main study objective was to determine whether higher-than-expected concentrations of AG in common obesity are associated with DE symptoms. MethodsThe study population included 84 women, aged 20–55 years, free of established EDs: 55 were severely obese (OB) and 29 were of normal weight (NW). OB participants were stratified into two groups according to their median concentration of fasting AG distribution. The OB women with a high fasting plasma ghrelin concentration (HGC) were compared with both OB women with a low fasting plasma ghrelin concentration (LGC) and NW women. Participants were assessed by the Eating Disorder Inventory (EDI-2), Three-Factor Eating Questionnaire (TFEQ) and Hospital Anxiety and Depression Scale (HADS). Fasting glucose, insulin, leptin and ghrelin plasma concentrations were also quantified. ResultsBetween the two AG groups of OB women, there was no statistical difference in either anthropometric or metabolic parameters, HADS, TFEQ or fasting hunger scores. However, the HGC group scored significantly higher than the LGC group on the drive-for-thinness subscale of EDI-2 (9.30±0.99 vs. 6.46±0.83, respectively; P=0.033). ConclusionResults support the hypothesis of a potential relationship between fasting plasma AG concentrations and ED risk, regardless of mood and anxiety. AG may be considered a potential biomarker of vulnerability for developing EDs.

Gender differences in ghrelin, nociception genes, psychological factors and quality of life in functional dyspepsia.

AIMto evaluate gender differences in the aspect of ghrelin, nociception-related genes and psychological aspects and the quality of life (QoL) in Korean functional dyspepsia (FD) patients.METHODSTotal of 191 persons were prospectively enrolled between March 2013 and May 2016 in Seoul National Bundang Hospital, and classified into control and FD group based on ROME III criteria. Questionnaire included assessment for dyspepsia symptoms, QoL and anxiety or depression. Preproghrelin and nociception genes in the gastric mucosa and plasma acyl/des-acyl ghrelin were measured.RESULTSLower level of plasma acyl ghrelin in FD patients compared to control was significant only in male (15.9 fmol/mL vs 10.4 fmol/mL, P = 0.017). Significantly higher mRNA expressions of nerve growth factor and transient receptor potential vanilloid receptor 1 were observed in male (P = 0.002 and P = 0.014, respectively) than in female. In contrast, female FD patients had a higher anxiety and depression score than male FD (P = 0.029), and anxiety score was correlated with epigastric pain only in female FD patients (female: Spearman rho = 0.420, P = 0.037). The impairment of overall QoL was more prominent in female FD patients than male patients (5.4 ± 0.3 vs 6.5 ± 0.3, P = 0.020).CONCLUSIONGender differences of ghrelin and nociception-related genes in male and psychological factors in female underlie FD symptoms. More careful assessment of psychological or emotional status is required particularly for the female FD patients.

Plasma acyl ghrelin and nonesterified fatty acids are the best predictors for hunger status in pregnant gilts.

Sows are usually restricted fed during pregnancy to maximize their reproductive efficiency, which may predispose sows to a state of hunger. However, an objective measurement of hunger status has not been established. In the present study, we examined the correlation of plasma hormones and NEFA and selected the best predictors for hunger status using pregnant gilts. Three different levels of feed intake (0.5, 1.0 and 2.0 × maintenance energy intake [0.5M, 1.0M and 2.0M, respectively]) were imposed from Day 28 to 34 of gestation to create different hunger statuses in pregnant gilts. Plasma hormones related to energy homeostasis and NEFA were analyzed to quantify their response to different levels of feed intake. A total of 18 gilts (197.53 ± 6.41 kg) were allotted to 1 of 3 dietary treatments using a completely randomized design. Results showed that BW change, ADG, and G:F from Day 28 to 34 of gestation were higher ( < 0.01) for gilts on the 2.0M feeding level than for gilts on the 0.5M feeding level. Plasma acyl ghrelin concentrations showed a relatively flat pattern during the 24-h period. Plasma acyl ghrelin and NEFA concentrations and areas under the curve (AUC) were greater ( < 0.05) in gilts on the 0.5M level of feed intake than in those on the 2.0M level of feed intake. No differences were observed among the 3 feeding levels in terms of plasma glucagon-like peptide 1 and leptin concentrations. Additionally, consumption time for 1.82 kg feed on Day 35 of gestation was longer ( < 0.01) in gilts fed the 2.0M level of feed intake from Day 28 to 34 of gestation than in those on the 0.5M level of feed intake. Simple linear regression results showed that the AUC of acyl ghrelin was the best predictor for consumption time ( = 0.82), whereas the AUC of NEFA was the best predictor for BW ( = 0.55) or backfat change ( = 0.42) from Day 28 to 34 of gestation. In conclusion, our data suggested that a relative flat pattern existed in pregnant gilts in terms of the diurnal plasma profile of acyl ghrelin and that the level of feed intake of pregnant gilts was negatively correlated with plasma concentrations of acyl ghrelin and NEFA, which, in turn, were negatively associated with feed consumption time. The AUC of acyl ghrelin and NEFA seemed to be the best predictors for hunger status of pregnant gilts.

Metabolic Syndrome is Associated with Lower Plasma Levels of Desacyl Ghrelin and Total Ghrelin in Asymptomatic Middle-aged Korean Men.

BackgroundDesacyl ghrelin is acylated by ghrelin O-acyltransferase (GOAT) and converted to acyl ghrelin. To date, little is known about the relationship among the levels of these two forms of ghrelin, GOAT level, and insulin resistance in Asian individuals. The purpose of this study was to determine the relationship between insulin resistance and the levels of plasma acyl ghrelin, desacyl ghrelin, and GOAT in asymptomatic middle-aged Korean men.MethodsThis cross-sectional study evaluated 78 asymptomatic middle-aged Korean men with metabolic syndrome (MS). We examined the correlation between the plasma levels of acyl ghrelin, desacyl ghrelin, and GOAT and sociodemographic, dietary, anthropometric, and metabolic parameters, as well as the association between insulin resistance and plasma levels of acyl ghrelin, desacyl ghrelin, and GOAT.ResultsThe levels of desacyl ghrelin and total ghrelin were significantly lower in the MS group than in the non-MS group (P<0.017, P=0.01, respectively). HOMA-IR values showed a significant negative correlation with desacyl ghrelin (r=−0.271, P=0.017) and total ghrelin (r=−0.271, P=0.016) levels. Acyl ghrelin and GOAT were not significantly correlated with HOMA-IR, and no correlation was found between the plasma levels of the two ghrelin types and GOAT.ConclusionThe plasma levels of desacyl ghrelin and total ghrelin in middle-aged Korean men with MS were lower than in those without MS. A significant negative correlation was observed between desacyl ghrelin level and HOMA-IR; however, no correlation was found between plasma levels of acyl ghrelin and GOAT and HOMA-IR.

322 Plasma acyl ghrelin and nonesterified fatty acids are the best indicators for hunger status in pregnant gilts

322 Plasma acyl ghrelin and nonesterified fatty acids are the best indicators for hunger status in pregnant gilts

Effects of different feeding levels during three short periods of gestation on gilt and litter performance, nutrient digestibility, and energy homeostasis in gilts.

The present study investigated the effects of different feeding levels during 3 short periods of gestation on gilt and litter performance, apparent total tract digestibility (ATTD) of energy and nutrients, and energy homeostasis in gilts. A total of 18 gilts were allotted to 1 of 3 dietary treatments using a completely randomized design. All gilts were fed 1 common corn-soybean meal-based diet with the amount of 1.0 × maintenance energy intake (100 × BW (BW) kcal ME/d) throughout gestation except 3 periods of 7 d when dietary treatments were imposed on d 27, d 55, and d 83 of gestation. During the 3 short periods, gilts were fed 1 of 3 different feeding levels: 0.5, 1.0, and 2.0 × maintenance energy level (0.5M, 1.0M, and 2.0M, respectively). Results showed that gilts on 2.0M feeding level had higher ( < 0.05) weight gain from d 27 to 109 of gestation (37.05 vs. 15.34 kg) and greater ( < 0.05) BW change, average daily gain, and gain to feed ratio during gestation periods 1 (d 27-34) and 3 (d 83-90) when compared with gilts on 0.5M feeding level. No differences ( > 0.10) in litter performance were observed among the 3 feeding levels. Additionally, the slopes of BW change in response to feeding levels in period 1 were 4.32 kg/0.5M change from 0.5M to 1.0M feeding level and 3.72 kg/0.5M change from 1.0M to 2.0M feeding level, respectively. There were quadratic ( < 0.05) effects of feeding levels on ATTD of dry matter and gross energy during periods 1 and 2 (d 55-62). Furthermore, fasting plasma concentrations of acyl ghrelin and nonesterified fatty acid (NEFA) in period 1 were greater ( < 0.01) in gilts on 0.5M feeding level than those on 2.0M feeding level. In conclusion, increasing feeding levels during 3 short periods increased primiparous sow performance during these short periods but did not affect litter performance. ATTD of energy and nutrients, and BW change efficiency were maximized for gilts on 1.0 M feeding level. The data also indicated that sows on the lowest feeding level were exposed to negative energy balance as evidenced by the higher plasma acyl ghrelin and NEFA concentrations.

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.

The effect of glutamate on ghrelin release in mice.

Ghrelin is abundantly produced in the stomach. Here, we found that glutamate decreased ghrelin expression and release in ghrelin-producing cells, and decreased levels of food intake and plasma acyl-ghrelin in mice. Treatment with siRNA of G protein-coupled receptor, family C, group 5, member B (GPRC5B) in ghrelin-producing cell lines completely blocked the effect of glutamate-induced ghrelin suppression. In addition, glutamate inhibited ghrelin release via the extracellular signal-regulated kinase (ERK) activity pathway, and stimulated CREB2 mRNA expression in ghrelin-producing cell lines. These results suggest that glutamate inhibits ghrelin release via ERK-CREB2 pathway. These results suggest that the GPRC5B-ERK-CREB2 pathway is involved in the inhibition of ghrelin expression and secretion in ghrelin cells.

Corticotropin-releasing factor overexpression in mice abrogates sex differences in body weight, visceral fat, and food intake response to a fast and alters levels of feeding regulatory hormones

BackgroundCorticotropin-releasing factor overexpressing (CRF-OE) male mice showed an inhibited feeding response to a fast, and lower plasma acyl ghrelin and Fos expression in the arcuate nucleus compared to wild-type (WT) mice. We investigated whether hormones and hypothalamic feeding signals are impaired in CRF-OE mice and the influence of sex.MethodsMale and female CRF-OE mice and WT littermates (4–6 months old) fed ad libitum or overnight fasted were assessed for body, adrenal glands and perigonadal fat weights, food intake, plasma hormones, blood glucose, and mRNA hypothalamic signals.ResultsUnder fed conditions, compared to WT, CRF-OE mice have increased adrenal glands and perigonadal fat weight, plasma corticosterone, leptin and insulin, and hypothalamic leptin receptor and decreased plasma acyl ghrelin. Compared to male, female WT mice have lower body and perigonadal fat and plasma leptin but higher adrenal glands weights. CRF-OE mice lost these sex differences except for the adrenals. Male CRF-OE and WT mice did not differ in hypothalamic expression of neuropeptide Y (NPY) and proopiomelanocortin (POMC), while female CRF-OE compared to female WT and male CRF-OE had higher NPY mRNA levels. After fasting, female WT mice lost more body weight and ate more food than male WT, while CRF-OE mice had reduced body weight loss and inhibited food intake without sex difference. In male WT mice, fasting reduced plasma insulin and leptin and increased acyl ghrelin and corticosterone while female WT showed only a rise in corticosterone. In CRF-OE mice, fasting reduced insulin while leptin, acyl ghrelin and corticosterone were unchanged with no sex difference. Fasting blood glucose was higher in CRF-OE with female > male. In WT mice, fasting increased hypothalamic NPY expression in both sexes and decreased POMC only in males, while in CRF-OE mice, NPY did not change, and POMC decreased in males and increased in females.ConclusionsThese data indicate that CRF-OE mice have abnormal basal and fasting circulating hormones and hypothalamic feeding-related signals. CRF-OE also abolishes the sex difference in body weight, abdominal fat, and fasting-induced feeding and changes in plasma levels of leptin and acyl ghrelin.

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.

Influence of Obestatin and Short-Term Treadmill Exercise on Plasma Acyl-Ghrelin and Body Weight in Wistar Rat

Background: Related reviews reveal that the impact of obestatin (with or without exercise) on the level of ghrelin has not been investigated. The present study investigates the possible effect of intraperitoneally (IP)-administrated obestatin and short-term exercise on serum acyl-ghrelin and body weight in rats. Methods: In present experimental study forty-five male rats weighing 100 ± 5 g were divided into five groups; Group 1: control group was normally reared, and did not receive any injections or exercise. Group 2 (placebo) was treated with basal solution (50 mL distilled water). Group 3 was referred to as obestatin group which was subjected to double-injection during the test with obestatin (10 μg obestatin/ rat). Group 4 was known as treadmill group which was subjected to treadmill exercise. Finally, group 5, known as obestatin /treadmill group (OT), was subjected to injection with obestatin and treadmill exercise. The exercise groups were trained for 3 weeks (run at 25 m/min for 60 minutes, 5 days/week).The data were analyzed with SPSS software version 16. Results: Two main parameters include body weight gain and serum acyl-ghrelin was assayed. The results indicate that body weight and ghrelin level in obestatin and OT groups did not significant changes compared with the control group (P < 0.001). However, treadmill group had less ghrelin level was different significantly from control group (P < 0.0001). Also, the treadmill group had the least weight gain (P < 0.0001). Conclusions: It was found that whereas short-term treadmill exercise significantly reduces serum acyl-ghrelin, IP-administration of obestatin had no significant impact on serum acyl-ghrelin and final body weight. The short-term treadmill exercise reduced weight gain rate. The results of the study indicated that the combination of obestatin injection and treadmill exercise had no significant impact on the measured variables.

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.

Plasma acylated and plasma unacylated ghrelin: useful new biomarkers in patients with neuroendocrine tumors?

To date, the value of fasting plasma acylated ghrelin (AG) and unacylated ghrelin (UAG) as potential novel biomarkers in patients with neuroendocrine tumors (NETs) is unknown. The aims of this study are to (i) compare fasting AG and UAG levels between nonobese, nondiabetic NET patients (N=28) and age- (±3 years) and sex-matched nonobese, nondiabetic controls (N=28); and (ii) study the relationship between AG, UAG, and AG/UAG ratios and biochemical (chromogranin-A (CgA) and neuron-specific enolase (NSE) levels) and clinical parameters (age at diagnosis, sex, primary tumor location, carcinoid syndrome, ENETS TNM classification, Ki-67 proliferation index, grading, prior incomplete surgery) in NET patients. Fasting venous blood samples (N=56) were collected and directly stabilized with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride after withdrawal. Plasma AG and UAG levels were determined by ELISA. Expression of ghrelin was examined in tumor tissue by immunohistochemistry. There were no significant differences between NET patients and controls in AG (median: 62.5 pg/mL, IQR: 33.1–112.8 vs median: 57.2pg/mL, IQR: 26.7–128.3, P=0.66) and UAG in levels (median: 76.6pg/mL, IQR: 35.23–121.7 vs median: 64.9, IQR: 27.5–93.1, P=0.44). No significant correlations were found between AG, UAG, and AG/UAG ratios versus biochemical and clinical parameters in NET patients with the exception of age at diagnosis (AG: ρ= −0.47, P=0.012; AG/UAG ratio: ρ= −0.50, P=0.007) and baseline chromogranin-A levels (AG/UAG ratio: ρ= −0.44, P=0.019). In our view, fasting plasma acylated and unacylated ghrelin appear to have no value as diagnostic biomarkers in the clinical follow-up of patients with NETs.