Total Ghrelin Levels Research Articles

Plasma ghrelin and risks of sex-specific, site-specific, and early-onset colorectal cancer: A Mendelian randomization analysis.

Epidemiological and laboratory-based studies have provided conflicting evidence for a role of ghrelin in colorectal cancer (CRC) development. We conducted two-sample Mendelian randomization (MR) analyses to evaluate evidence for an association of circulating ghrelin and CRC risk overall and by sex, cancer subsite and age at diagnosis. Genetic instruments proxying plasma total ghrelin levels were obtained from a recent genome-wide association study of 54,219 participants. Summary data for CRC risk were obtained from a recent meta-analysis of several genetic consortia (up to 73,673 cases and 86,854 controls). A two-sample MR approach and several sensitivity analyses were applied. We found no evidence for an association of genetically-predicted plasma total ghrelin levels and CRC risk (0.95, 95% confidence interval: 0.81-1.12; R2 of ghrelin genetic instruments: 4.6%), with similarly null results observed when stratified by sex, anatomical subsite, and for early-onset CRC. Our study suggests that plasma ghrelin levels are unlikely to have a causal relationship with overall, early-onset, and sex- and cancer subsite-stratified CRC risk. This large-scale analysis adds to the growing body of evidence that plasma total ghrelin levels are not associated with CRC risk.

The Impact of Exercise Intensity and Sex on Endogenous Ghrelin Levels and Appetite in Healthy Humans.

Ghrelin circulates in acylated (AG) and deacylated (DAG) forms, which are known to affect appetite. Although acute exercise has been shown to modulate ghrelin levels, data on the impact of exercise intensity on AG and DAG levels and their effects on appetite are sparse and primarily limited to males. To investigate the effect of exercise intensity and sex on ghrelin levels and appetite in untrained humans. Eight males (age: 43.1 ± 10.9 years; body mass index [BMI]: 22.2 ± 1.7 kg/m2; peak oxygen consumption [VO2peak]: 36.3 ± 6.4 mL/kg/min) and 6 females (age: 32.2 ± 11.1 years; BMI: 22.7 ± 1.0 kg/m2; VO2peak: 29.2 ± 4.0 mL/kg/min) completed a maximal graded cycle ergometer lactate threshold (LT)/VO2peak test. These data were used to determine the exercise intensity on 3 subsequent randomized control or calorically matched cycle exercise bouts: (1) CON, no exercise; (2) MOD, the power output at LT; (3) HIGH, the power output associated with 75% of the difference between LT and VO2peak. Perception of appetite was analyzed using visual analog scales. Females had higher levels of total ghrelin (TG) (P = .03) and DAG (P = .01) at baseline than males. Both groups exhibited reduced DAG levels in HIGH compared with MOD and CON (P < .0001-.004); however, only females had significantly reduced AG in HIGH (P < .0001). Hunger scores were higher in MOD than in CON (P < .01). High-intensity may be superior to moderate-intensity exercise for reducing ghrelin levels and modifying hunger, and sex may impact this response.

Type of food available during recovery from acute restraint stress affects plasma levels of total ghrelin but not plasma corticosterone in male rats: A pilot study

Exposure to a stressor can alter energy intake, potentially resulting in overall changes to body weight. However, our understanding of the relationship between stress and food intake remains incomplete. In these studies, we evaluated whether the type of food available for consumption after stress exposure may be an important determinant of plasma corticosterone (CORT) and ghrelin levels after restraint stress in male rats. Male rats were exposed to 1 h restraint stress or handling control, then given access to a test food to assess how access to different types of food impacted plasma CORT and ghrelin post-stressor. Our results indicated that the type of test food did not impact the plasma CORT response after restraint stress. In contrast, plasma ghrelin levels were differentially altered by the type of test food available in the experiment. These findings suggest the importance of considering the type of test food available in studies examining interactions between stress and feeding, and may also point to a crucial role of the timing of prior palatable food access in such experiments.

Exploring the impact of lifestyle and environmental exposures on appetite hormone levels in children and adolescents: An observational study

BackgroundAppetite hormones are considered a promising target in fighting obesity as impaired appetite hormone levels have already been associated with obesity. However, further insights in the drivers of appetite hormone levels are needed. ObjectivesIn this study, we investigated the associations of fasting appetite hormone levels with lifestyle and environmental exposures in children and adolescents. MethodsA total of 534 fasting blood samples were collected from children and adolescents (4-16y,50% boys) and appetite hormone levels (glucagon-like peptide-1 (GLP-1), peptide YY (PYY), pancreatic polypeptide (PP), leptin and ghrelin) were measured. Exposures included dietary quality (fiber-rich food intake, sugar propensity, fat propensity), psychosocial stress (happiness, negative emotions, negative life events and emotional problems), sleep duration, physical activity and environmental quality (long term black carbon (BC), particulate matter <2.5 μM (PM2.5), nitrogen dioxide (NO2) exposure, and green space in a 100 m and 2000 m radius around the residence). A multi-exposure score was calculated to combine all the exposures at study in one measure. Associations of individual exposures and multi-exposure score with appetite hormone levels were evaluated using linear mixed regression models adjusting for sex, age, socioeconomic status, waist-to-height ratio and multiple testing. ResultsGLP-1 was associated with air pollution exposure (NO2 β* = -0.13, BC β* = -0.15, PM2.5 β* = -0.16, all p < 0.001). Leptin was associated with green space in a 100 m radius around the residence (β* = -0.11; p = 0.002). Ghrelin was associated with negative emotions (active ghrelin β* = -0.16; p = 0.04, total ghrelin β* = -0.23; p = 0.0051) and happiness (active ghrelin β* = 0.25; p < 0.001, total ghrelin β* = 0.26; p < 0.001). Furthermore, total ghrelin levels were associated with the multi-exposure score, reflecting unhealthy exposures and lifestyle (β* = -0.22; p = 0.036). DiscussionOur findings provide new insights into the associations of exposures with appetite hormone levels, which are of high interest for preventive obesity research. Further research is crucial to reveal the underlying mechanisms of the observed associations.

Leptin, Nesfatin-1, Orexin-A, and Total Ghrelin Levels in Drug-Naive Panic Disorder.

This study aimed to examine the changes in serum nesfatin-1, leptin, orexin-A, and total ghrelin levels of patients diagnosed with drug-naive panic disorder (PD) before and after six weeks of the treatment and to compare the findings with the healthy subjects. The neuropeptides were measured in venous blood samples taken from 32 patients and 32 healthy subjects. The blood samples of the patients who used paroxetine 20 mg/day plus alprazolam 0.5 mg/day were retaken again after six weeks. Measurements were performed with the Enzyme-Linked Immunosorbent Assay (ELISA) method. Serum nesfatin-1, leptin, orexin-A and total ghrelin levels of the patient group were found to be significantly lower than the control group (p<0.001, p<0.001, p<0.001, and p<0.001, respectively). When the serum nesfatin-1, leptin, orexin-A and total ghrelin levels of the patient group were compared before and after treatment, significant differences were found in terms of orexin-A and total ghrelin levels (p=0.046, p<0.001, respectively). However, no significant differences were found in terms of nesfatin-1and leptin levels (p=0.205, p=0.988, respectively). This study reports that PD, like other anxiety disorders, may affect serum nesfatin-1, leptin, orexin-A, and total ghrelin levels, and there may be a relationship between PD treatment and the levels of these neuropeptides. The variability of this relationship among the neuropeptides examined indicates that various factors other than treatment play a role in this process.

Ghrelin and depressive symptoms in patients with first-episode drug-naïve major depressive disorder: The mediating role of hypothalamic-pituitary-adrenal axis.

Major depressive disorder (MDD) is one of the global burdens of disease, and its pathogenesis remains unclear. An increasing amount of research indicates that ghrelin regulates mood in patients with MDD. Still, current results are inconsistent, and the mechanisms underlying how ghrelin modulates depressive symptoms are inconclusive, especially in first-episode drug-naïve MDD patients. Therefore, this study aims to investigate the relationship and potential mechanism between ghrelin and first-episode drug-naïve MDD. Ninety first-episode drug-naïve MDD patients and 65 healthy controls (HCs) were included. Hamilton Depression Scale (HAMD-17) as a measure of depressive symptoms. Plasma levels of ghrelin and hypothalamic-pituitary-adrenal axis (HPA-axis) hormones were measured in all participants. Compared to HCs, the ghrelin levels were higher in the MDD (p < .001) and still showed significance after covarying for sex, age, and Body Mass Index (BMI). Ghrelin was positively related to corticotropin-releasing-hormone (CRH) levels (r = .867, p < .001), adrenocorticotropic hormone (ACTH) levels (r = .830, p < .001), and cortisol levels (r = .902, p < .001) in partial correlation analysis. In addition, there was a positive correlation between HAMD total score and ghrelin levels (r = .240, p = .026). Other than that, the HAMD total score also had a positive correlation with the CRH (r = .333, p = .002) and cortisol (r = .307, p = .004) levels. Further mediation analysis demonstrated that the relationship between ghrelin and HAMD total score was mediated by CRH (ab-path; β = .4457, 95% CI = 0.0780-1.0253, c-path; β = .2447, p = .0260, c'-path; β = -.2009, p = .3427). These findings revealed that plasma ghrelin provides a pivotal link to depressive symptoms in first-episode drug-naive MDD patients. CRH mediated the relationship between ghrelin and HAMD total score. It might provide new insights into understanding the pathogenesis of MDD, contributing to intervention and treatment from this approach.

Changes in Circulating Acylated Ghrelin and Neutrophil Elastase in Diabetic Retinopathy.

Background and Objectives: The role and the levels of ghrelin in diabetes-induced retinal damage have not yet been explored. The present study aimed to measure the serum levels of total ghrelin (TG), and its acylated (AG) and des-acylated (DAG) forms in patients with the two stages of diabetic retinopathy (DR), non-proliferative (NPDR) and proliferative (PDR). Moreover, the correlation between serum ghrelin and neutrophil elastase (NE) levels was investigated. Materials and Methods: The serum markers were determined via enzyme-linked immunosorbent assays in 12 non-diabetic subjects (CTRL), 15 diabetic patients without DR (Diabetic), 15 patients with NPDR, and 15 patients with PDR. Results: TG and AG serum levels were significantly decreased in Diabetic (respectively, p < 0.05 and p < 0.01 vs. CTRL), NPDR (p < 0.01 vs. Diabetic), and in PDR patients (p < 0.01 vs. NPDR). AG serum levels were inversely associated with DR abnormalities (microhemorrhages, microaneurysms, and exudates) progression (r = -0.83, p < 0.01), serum neutrophil percentage (r = -0.74, p < 0.01), and serum NE levels (r = -0.73, p < 0.01). The latter were significantly increased in the Diabetic (p < 0.05 vs. CTRL), NPDR (p < 0.01 vs. Diabetic), and PDR (p < 0.01 vs. PDR) groups. Conclusions: The two DR stages were characterized by decreased AG and increased NE levels. In particular, serum AG levels were lower in PDR compared to NPDR patients, and serum NE levels were higher in the PDR vs. the NPDR group. Together with the greater presence of retinal abnormalities, this could underline a distinctive role of AG in PDR compared to NPDR.

High-Fat Diet Induces Resistance to Ghrelin and LEAP2 Peptide Analogs in Mice.

Recent data suggest that the orexigenic peptide ghrelin and liver-expressed antimicrobial peptide 2 (LEAP2) have opposing effects on food intake regulation. Although circulating ghrelin is decreased in obesity, peripheral ghrelin administration does not induce food intake in obese mice. Limited information is available on ghrelin resistance in relation to LEAP2. In this study, the interplay between ghrelin and LEAP2 in obesity induced by a high-fat (HF) diet in mice was studied. First, the progression of obesity and intolerance to glucose together with plasma levels of active and total ghrelin, leptin, as well as liver LEAP2 mRNA expression at different time points of HF diet feeding was examined. In addition, the impact of switch from a HF diet to a standard diet on plasma ghrelin and LEAP2 production was studied. Second, sensitivity to the stable ghrelin analogue [Dpr3]Ghrelin or our novel LEAP2 analogue palm-LEAP2(1-14) during the progression of HF diet-induced obesity and after the switch for standard diet was investigated. Food intake was monitored after acute subcutaneous administration. HF diet feeding decreased both active and total plasma ghrelin and increased liver LEAP2 mRNA expression along with intolerance to glucose and the switch to a standard diet normalized liver LEAP2 mRNA expression and plasma level of active ghrelin, but not of total ghrelin. Additionally, our study demonstrates that a HF diet causes resistance to [Dpr3]Ghrelin, reversible by switch to St diet, followed by resistance to palm-LEAP2(1-14). Further studies are needed to determine the long-term effects of LEAP2 analogues on obesity-related ghrelin resistance.

FRI074 Rise In Fasting Ghrelin Level In Response To Weight Loss Predicts Future Weight Regain In The POUNDS LOST Trial

Abstract Disclosure: J. Tong: None. Y. Heianza: None. E.A. Schur: None. F. Sacks: None. L. Qi: None. E.J. Boyko: None. Weight loss maintenance is a challenging problem commonly encountered in obesity management. The biological mechanism for weight regain following diet-induced weight loss is not well understood. The orexigenic gut hormone ghrelin increases appetite and food intake and promote positive energy balance. We aim to investigate whether weight-loss induced fasting ghrelin changes predict subsequent weight regain in the POUNDS LOST trial. Methods: This study included 244 overweight or obese adults (age: 52.9±8.8 yr; 66% female; BMI 32.4±3.9 kg/m2 [mean ± SD]) randomly assigned to 1 of 4 weight-loss diets varying in macronutrient intake who had fasting plasma total ghrelin levels measured at baseline, 6 and 24 months after the intervention. We examined associations between fasting ghrelin levels changes between baseline and 6-months (weight change: -7.1±5.3 kg) and body weight change between 12 and 24 months (3.2±3.9 kg). Results: Fasting plasma ghrelin level increased significantly at 6 months (from 487.3±251.1 to 574.0±274.5 pg/mL) and remained elevated at 24 months despite weight regain (684.0±411.0 pg/mL). Increases in ghrelin level from baseline to 6 months (86.7±167.4 pg/mL) were correlated with weight regain from 12 to 24 months (p=0.018). The association was unchanged after adjustment for age, sex, race, and diet assignment at baseline; fat and carbohydrate craving scores, hunger and fullness ratings, dietary restraint and disinhibition scores measured at 6 months, prior to onset of weight regain. Conclusions: Fasting ghrelin levels rose in response to diet-induced weight loss and persisted for 2 years despite weight regain. Ghrelin change during the weight loss phase predicts subsequent weight regain independent of appetite and craving measures. Understanding the mechanistic connection between ghrelin action and weight regain may shed light on novel approaches to weight loss maintenance. Presentation: Friday, June 16, 2023

Endogenous Ghrelin Levels and Perception of Hunger: A Systematic Review and Meta-Analysis.

Ghrelin is an orexigenic hormone primarily released by the stomach and has 2 isoforms: acylated ghrelin (AG) and de-acylated ghrelin (DAG), that appear to have different functions in humans. To perform a systematic review and meta-analysis of the association between plasma concentrations of total ghrelin (TG), AG, and DAG and perceptions of hunger in healthy adults. The following criteria were used for inclusion: 1) sample contained adults ≥18 y of age, 2) body mass index [BMI kg/m2] was ≥18.5, 3) ghrelin was sampled through blood, 4) subjective hunger was measured on a validated scale, 5) study reported a Pearson product correlation of ghrelin or had relevant figure(s) for data extraction, 6) participants were healthy with no overt disease, 7) protocols contained no physical activity or weight loss medication that suppressed appetite, 8) interventions were conducted without environmental manipulations. Moderators assessed were age, BMI, percentage of body fat (%BF), macronutrient content of test meals, energy intake (kcals), sex, and ghrelin isoform (AG, DAG, or TG). The analysis included 47 studies (110 trials, n = 1799, age: 31.4 ± 12.0 y, BMI: 26.0 ± 4.75) and measured AG (n = 47 trials), DAG (n = 12 trials), and TG (n = 51 trials). The overall model indicated that ghrelin concentrations and perceptions of hunger were moderately correlated (r = 0.43, P < 0.001), and ghrelin isoform significantly moderated this relationship (AG: r = 0.60, P < 0.001; TG: r = 0.215, P=0.01; DAG: r = 0.53, P = 0.695). Other significant moderators included age (b = -0.02, P = 0.01), BMI (b = -0.03, P = 0.05), %BF (b=-0.03, P = 0.05), energy intake (b = 0.0003, P = 0.04), and percentage of carbohydrates of test meals (b = 0.008, P = 0.05). Ghrelin is associated with perceptions of hunger in humans, and this relationship is strengthened when AG is isolated; thus, AG may have a large impact on hunger signals in various populations. Future research should attempt to understand the role of DAG in hunger sensations.

Leptin, but not ghrelin, is associated with food addiction scores in a population-based subject sample.

Ghrelin and leptin are both peptide hormones and act as opposing players in the regulation of hunger, satiety and energy expenditure. Leptin reduces appetite and feelings of hunger and is secreted mainly by adipocytes, while ghrelin increases appetite and food intake and reduces metabolic rate. Both hormones have been implicated in addictive disorders. Ghrelin was shown to have pro-addictive effects while leptin's role in addiction yields more conflicting results. Their involvement in the regulation of both food intake and addictive behaviors make them interesting candidates when investigating the regulation of food addiction. However, only few human studies have been performed and large-scale studies are lacking to date. We aimed to investigate the association between total ghrelin and leptin serum levels with scores in the Yale Food Addiction Scale (YFAS). Subjects were recruited in the LIFE Adult cohort. 909 subjects were included in the analysis and we performed univariate multiple linear regression models, adjusted for age, sex (in total group analyses only), alcohol consumption, smoking status, BMI scores, cortisol concentrations, Center for Epidemiological Studies Depression Scale (CES-D) and the 7-item Generalized Anxiety Disorder Scale (GAD-7) sum scores. The dependent variable was the YFAS score. In men, leptin serum levels showed a significant positive association (standardized β = 0.146; p = 0.012) with the YFAS score. This finding was confirmed in an extreme-group comparison: men in the highest quartile of leptin levels had significantly higher YFAS sum scores than men in the lowest quartile (1.55 vs. 1.18; p = 0.00014). There was no association with YFAS sum score in the total group (standardized β = -0.002; p = 0.974) or in women (standardized β = -0.034; p = 0.674). Total serum ghrelin showed no association with YFAS sum score neither in the total group (standardized β = -0.043; p = 0.196) nor in men (n = 530; standardized β = -0.063; p = 0.135) or women (n = 379; standardized β = -0.035; p = 0.494). Our findings are in line with previous literature and suggest that total ghrelin serum levels are not associated with food addiction scores. Leptin had been previously shown to be associated with food addiction and we confirmed this finding for men in a large, population-based approach.

Free-access intravenous alcohol self-administration in social drinkers and individuals with alcohol use disorder: Evaluation of relationships with phosphatidylethanol and self-reported alcohol consumption.

The free-access (FA) intravenous alcohol self-administration (IV-ASA) paradigm is an experimental approach that can identify modulators of alcohol consumption in humans. Moreover, the outcome measures of IV-ASA paradigms are associated with self-reported alcohol intake using the timeline follow-back method (TLFB). To evaluate how FA IV-ASA reflects drinking in real life, we examined the relationship between an objective marker of recent alcohol intake, phosphatidylethanol in blood (B-PEth), and TLFB and measures obtained during IV-ASA in individuals with alcohol use disorder (AUD) and social drinkers (SD). We also explored the associations between these measures and gut-brain peptides involved in AUD pathophysiology. Thirty-eight participants completed a laboratory session in which they self-administered alcohol intravenously. The safety limit was 200 mg%, and main outcomes were mean and peak breath alcohol concentrations (BrAC). Blood samples were drawn prior to IV-ASA and subjective alcohol effects were rated during the experiment. The study sample comprised 24 SD and 14 participants with DSM-5 mild AUD. Although BrACs were not associated with B-PEth or TLFB in the full sample or AUD subgroup, there was an association with TLFB in SD. In both subgroups, BrACs were associated with alcohol craving but with differential timing. Total ghrelin levels were higher in AUD participants than in SD. No associations between B-PEth levels and achieved BrACs were observed in the mild AUD group, the SD group, or the full sample. The ability for FA IV-ASA to reflect recent drinking was confirmed only for TLFB in SD, whereas there were no associations within the smaller subsample of participants with mild AUD or in the full sample. Further studies that include a larger AUD sample are warranted. The association of BrACs with craving for alcohol suggests that the IV-ASA method may be useful for assessing interventions that target craving. This could be explored by using the FA IV-ASA model to evaluate the effects on craving of approved pharmacotherapies for AUD.

Childhood sexual abuse is associated with higher total ghrelin serum levels in adulthood: results from a large, population-based study

Ghrelin is an orexigenic peptide hormone synthesized in times of stress and hunger and alterations of the ghrelin system following acute stressors could be repeatedly shown in humans. However, little data exists on long-term effects of trauma on the ghrelin system. We aimed to investigate the influence of childhood trauma on total ghrelin serum levels in a large, population-based study. Total serum ghrelin was measured in 1666 participants of a population-based cross-sectional study (‘LIFE study’). The Childhood Trauma Screener (CTS) was used for the assessment of childhood trauma in the final sample (n = 1086; mean age: 57.10 ± 16.23 years; 632 males, 454 females). Multiple linear regression analyses and generalized linear models were chosen to examine the association between childhood trauma and total serum ghrelin concentrations. Childhood sexual abuse went along with significantly higher ghrelin serum levels in the total sample (β = 0.114, t = 3.958; p = 0.00008) and in women (β = 0.142, t = 3.115; p = 0.002), but not in men (β = 0.055; t = 1.388; p = 0.166). Women with severe emotional neglect in the childhood had higher ghrelin levels than those without (odds ratio = 1.204; p = 0.018). For the CTS Sum Score and other CTS sub-scale scores, no significant association with ghrelin serum levels was found. Our study is the first to show associations between childhood sexual trauma and total ghrelin levels in adults in a large, community-based sample. Our results should initiate further research of the role of ghrelin in human stress response in prospective study designs.

The role of ghrelin peptide among a sample of Egyptian patients with first episode of major depressive disorder

BackgroundMajor depressive disorder (MDD) is a prominent psychiatric disorder that significantly reduces living quality and increases the risk of suicide. Ghrelin influences the central nervous system (CNS) and impacts reward, inspiration, and signaling pathways in addition to acting as an appetite signal. This case-controlled comparative study focused on the association between serum ghrelin levels and MDD. The study was done during September 2021 and March 2022 on 25 people with MDD and 25 healthy controls. SCID-1 and the Ham-D 17 scales were used to evaluate the cases. The GHQ scale was used to evaluate the controls. The serum ghrelin levels of all samples were determined. The findings were presented, and statistically analyzed to perform an accurate assessment.ResultsThere were 50 subjects: 25 cases of MDD and 25 healthy matched controls with non-statistically significant difference to cases as regard gender, marital status, residence, education, age, height, weight and body mass index (BMI). Total serum ghrelin levels among our cases showed a mean value of 4.152, while the controls showed markedly low values, with a mean value of 0.436, showing a statistically significant difference between both groups with p < 0.001. Furthermore, Post Hoc analysis by least significant difference showed a significant difference between mild-severe and moderate-severe groups, although there was no statistically significant difference between mild and moderate groups.ConclusionsThere was a significant indirect correlation between serum ghrelin level and severity of the illness. Further investigations via longitudinal studies and on larger samples are recommended to settle specific causal paths between the two variables.

The role of serum gastric peptide ghrelin hormone level in irritable bowel syndrome at Zagazig University Hospitals

Generalized dysmotility of the gastrointestinal tract develops in individuals with irritable bowel syndrome (IBS). The ghrelin hormone appears to be critical in controlling gastrointestinal motility. We aimed to evaluate serum ghrelin levels in people with IBS and to demonstrate its role in IBS pathophysiology. This study included 32 individuals with IBS (16 with constipation and 16 with diarrhea) and 16 healthy individuals as controls. Blood specimens were collected from patients and controls following an overnight fast. Total ghrelin level was detected in plasma by commercially available ELISA Kit. There were significant differences in the serum levels of ghrelin between the control group and both types of IBS. The mean±SD of ghrelin level in the control group was 2.608±0.714 pg/ml, and that of both types of IBS was 5.782±2.450 pg/ml (P-value<0.001). There was a significant variation between the control and IBS-D groups (mean±SD: 7.838±1.687 pg/ml, p-value<0.001). Also, we indicated a considerable difference between the control and IBS-C groups (mean±SD: 3.726±0.740 pg/ml, P-value<0.001). In comparing the IBS-D group and IBS-C group, we found a highly considerable variation between the two groups (p-value<0.001). This means that serum ghrelin levels were significantly greater in IBS-D than in IBS-C and the control group. Our findings concluded that serum ghrelin level was higher among the IBS-D group than in the IBS-C and control groups. The ghrelin hormone may play a vital role in IBS pathophysiology.

Total sleep deprivation decreases saliva ghrelin levels in adolescents.

Ghrelin, a regulator of food intake and energy expenditure, has been shown to be associated with insufficient sleep. The goal of the present study was to investigate the effect of a single night of total sleep deprivation on fasting saliva ghrelin and on nocturnal variation of saliva ghrelin concentration. A further aim of the study was to investigate the influence of body mass index on changes in saliva ghrelin levels. Altogether 35 adolescents (18 boys; age: 13.8 ± 1.14 years) were studied on two subsequent days (sleep and total sleep deprivation). Saliva samples were collected during the two experimental nights at 21:00 hours, 01:00 hours and 06:00 hours. Total-ghrelin concentration showed a continuous increase from the evening until 06:00 hours. This increase was blunted significantly (p=0.003) by total sleep deprivation. Total-ghrelin level was significantly lower (p=0.02) during total sleep deprivation at 06:00 hours (median 403.6pg ml-1 ; 95% confidence interval: 343.1-468.9pg ml-1 ) as compared with values during the sleep condition (median 471.2pg ml-1 ; 95% confidence interval: 205.4-1578.7pg ml-1 ). Acyl-ghrelin levels did not present any change at the three time points, and were not affected by total sleep deprivation. Stratifying the study population according to body mass index (normal weight and overweight/obese groups), the blunting effect of total sleep deprivation was more pronounced in the obese/overweight group (sleep: median 428.2pg ml-1 ; 95% confidence interval: 331.3-606.9pg ml-1 versus total sleep deprivation: median 333.1pg ml-1 ; 95% confidence interval: 261.5-412.9pg ml-1 ; p=0.0479). Saliva total-ghrelin concentrations gradually increased during the night, and total sleep deprivation significantly blunted this increase. This blunting effect was mainly observed in subjects with overweight/obesity. The physiological and clinical implications of the present observation are to be clarified by further studies.

Ghrelin Bridges DMV Neuropathology and GI Dysfunction in the Early Stages of Parkinson's Disease.

Ghrelin contributes to the communication between the brain and gastrointestinal (GI) tract. Both decreased ghrelin levels and functional GI disorders are early events in Parkinson's disease (PD) patients and animal models. However, the reason is not clear. Here it is found that choline acetyltransferase (ChAT)‐positive neurons in the dorsal motor nucleus of the vagus nerve (DMV), are lost in PD transgenic mice. In response to the selective damaging of DMV neurons with mu p75‐SAP, a rapid reduction both in plasma total and active ghrelin levels is observed. While by contrast, chemogenetic activation of DMV cholinergic neurons can increase the plasma ghrelin levels. Impairment of cholinergic neurons is accompanied by GI disorders, including decreased stool wet weight, stool dry weight, small intestine advancing rate, and gastric emptying rate, while exogenous ghrelin treatment can partially ameliorate GI dysfunction of A53T α‐synuclein transgenic mice. Using pseudorabies virus retrograde trace method, the existence of a direct pathway from the stomach fundus to the DMV is shown. Taken together, the findings suggest that the reduction in plasma ghrelin levels in the early stages of PD may be the result of the lesion of cholinergic neurons in the DMV, thus linking neurodegeneration and GI dysfunction in PD.

G-CuP: the effect of a forced oral glucose intake on alcohol craving and mesolimbic cue reactivity in alcohol dependence—study protocol of a randomized, double-blind, placebo-controlled crossover study

BackgroundMultiple studies indicate that a lower plasma level of the acetylated form of the appetite-regulating hormone ghrelin and higher plasma levels of insulin lead to a reduction in subjective alcohol craving and a reduced mesolimbic cue reactivity in functional magnetic resonance imaging (fMRI) when being exposed to alcohol-associated stimuli. The ghrelin level can physiologically be reduced by the induction of stomach distension and the ingestion of glucose or lipids.MethodsA total of 108 alcohol-dependent patients aged between 18 and 65 years are examined in the randomized, double-blind, placebo-controlled crossover study. After collecting demographic and psychometric data, participants take part in an alcohol exposure session. Afterwards, the participants go through the intervention condition (oral glucose intake) and the control condition (placebo intake) in a randomized order on two examination days. Blood samples are taken repeatedly (every 10 min) during the study course on both measuring days to determine changes in acetylated and total ghrelin and insulin plasma levels. In parallel, subjective alcohol craving after the glucose or placebo intake as the primary outcome is assessed using the Alcohol Urge Questionnaire (AUQ) and a visual analog scale (VAS). To examine the mesolimbic cue reactivity as the secondary outcome, a fMRI measurement is conducted while being exposed to alcohol-related stimuli. Appropriate statistical analysis will be used for the evaluation of the outcomes.DiscussionIf successful, the results of this study could offer alcohol-dependent patients a new potential option for acute short-term reduction of alcohol craving and thus prevent relapses and prolong periods of abstinence in the long term.Trial registrationGerman Clinical Trials Register DRKS00022419 (UTN: U1111-1278-9428). Retrospectively registered on September 15, 2020.

Intestinal permeability and appetite regulating peptides-reactive immunoglobulins in severely malnourished women with anorexia nervosa

In the last decades, the role of microbiota-gut-brain axis has emerged in the regulation of eating behavior and in the pathophysiology of anorexia nervosa (AN) that remains poorly understood. Particularly, a gut-derived dysregulation of immune response has been proposed leading to immunoglobulins directed against appetite-regulating peptides. However, intestinal permeability in patients with anorexia nervosa has been poorly documented. In the present prospective case-control study, we thus compared intestinal permeability, appetite-regulating peptides and their reactive immunoglobulins measured in severely malnourished women with AN (n=17; 28 [21-35] y; 14.9 [14.1-15.2] kg/m2) to healthy volunteers (HV, n=34; 26 [23-35] y; 22.3 [20.6-23.6] kg/m2). Patients with AN exhibited an increased urinary lactulose/mannitol ratio, both in 0-5h (0.033 [0.013-0.116]) and 5-24h samples (0.115 [0.029-0.582]), when compared to HV (0.02 [0.008-0.045], p=0.0074 and 0.083 [0.019-0.290], p=0.0174, respectively), suggesting an increased intestinal permeability. Urinary excretion of sucralose and plasma zonulin were not different. The levels of plasma total ghrelin and desacyl-ghrelin were increased in patients with AN compared to HV, whereas plasma leptin concentration was decreased. In addition, αMSH remained unchanged compared to HV. Finally, we did not observe any modification of the levels of total or free αMSH, leptin or ghrelin-reactive immunoglobulin G and M, as well as for their affinity properties. Only, a weak decrease of the dissociation constant (kd) for acyl-ghrelin-reactive IgG was observed in patients with AN (p=0.0411). In conclusion, severely malnourished patients with AN show a higher intestinal permeability than HV without evidence of an effect on appetite regulating peptides-reactive immunoglobulins.

Association Between Self-rating Depression Scores and Total Ghrelin and Adipokine Serum Levels in a Large Population-Based Sample.

BackgroundGhrelin and the adipokines leptin and adiponectin have been suggested to be involved in mood and anxiety regulation and to be altered in affective disorders. However, studies investigating the association between ghrelin, leptin and adiponectin and depressive symptomatology are scarce but might contribute to a better understanding of their involvement in mood regulation. We thus aimed investigating the association between depressive symptomatology and total ghrelin as well as leptin and adiponectin serum levels in a large population-based sample.MethodsTotal serum ghrelin, adiponectin and leptin levels were determined in 1666 subjects of a population-based cross-sectional study (“LIFE”). The Center for Epidemiological Studies Depression Scale (CES-D) and the Inventory of Depressive Symptoms – Self Rating (IDS-SR) were administered. Multiple linear regression analyses were conducted to examine the association between total serum ghrelin, leptin and adiponectin and the intensity of depressive symptoms.ResultsIn the total sample (n = 1,092), neither ghrelin nor leptin or adiponectin serum levels showed a significant association with CES-D or IDS-SR sum scores (N = 1,092) or in depressed/non-depressed subjects. Leptin serum levels showed a significantly positive association with IDS-SR sum scores in elderly men (≥60 years; β = 0.122, 95% CI: 0.009; 0.236; p = 0.035).ConclusionOur study suggests that peripheral levels of ghrelin and adipokines in a cross-sectional study design might not be sufficient to measure their involvement in depression, suggesting that associations are more complex and multi-layered.