Des-acyl Ghrelin Levels Research Articles

Des-acyl ghrelin reduces alcohol intake and alcohol-induced reward in rodents

The mechanisms contributing to alcohol use disorder (AUD) are complex and the orexigenic peptide ghrelin, which enhances alcohol reward, is implied as a crucial modulator. The major proportion of circulating ghrelin is however the non-octanoylated form of ghrelin, des-acyl ghrelin (DAG), whose role in reward processes is unknown. As recent studies show that DAG decreases food intake, we hypothesize that DAG attenuates alcohol-related responses in animal models. Acute and repeated DAG treatment dose-dependently decreased alcohol drinking in male and female rats. In these alcohol-consuming male rats, repeated DAG treatment causes higher levels of dopamine metabolites in the ventral tegmental area, an area central to reward processing. The role of DAG in reward processing is further supported as DAG prevents alcohol-induced locomotor stimulation, reward in the conditioned place preference paradigm, and dopamine release in the nucleus accumbens in male rodents. On the contrary, DAG does not alter the memory of alcohol reward or affect neurotransmission in the hippocampus, an area central to memory. Further, circulating DAG levels are positively correlated with alcohol drinking in female but not male rats. Studies were conducted in attempts to identify tentative targets of DAG, which currently are unknown. Data from these recombinant cell system revealed that DAG does not bind to either of the monoamine transporters, 5HT2A, CB1, or µ-opioid receptors. Collectively, our data show that DAG attenuates alcohol-related responses in rodents, an effect opposite to that of ghrelin, and contributes towards a deeper insight into behaviors regulated by the ghrelinergic signaling pathway.

Peripheral Biomarkers of Anorexia Nervosa: A Meta-Analysis.

The pathogenesis of anorexia nervosa (AN) has been hypothesized to involve several biological systems. However, reliable biomarkers for AN have yet to be established. This study was aimed to identify statistically significant and clinically meaningful peripheral biomarkers associated with AN. A systematic literature search was conducted to identify studies published in English from inception until 30 June 2022. We conducted two-level random-effects meta-analyses to examine the difference between AN and comparison groups across 52 distinct biomarkers and found that acylated ghrelin, adrenocorticotropic hormone (ACTH), carboxy-terminal collagen crosslinks (CTX), cholesterol, cortisol, des-acyl ghrelin, ghrelin, growth hormone (GH), obestatin, and soluble leptin receptor levels were significantly higher in cases of AN compared with those in non-AN controls. Conversely, C-reactive protein (CRP), CD3 positive, CD8, creatinine, estradiol, follicle-stimulating hormone (FSH), free thyroxine, free triiodothyronine, glucose, insulin, insulin-like growth factor 1 (IGF-1), leptin, luteinizing hormone, lymphocyte, and prolactin levels were significantly lower in AN compared with those in non-AN controls. Our findings indicate that peripheral biomarkers may be linked to the pathophysiology of AN, such as processes of adaptation to starvation. Scientific investigation into peripheral biomarkers may ultimately yield breakthroughs in personalized clinical care for AN.

Ghrelin is associated with an elevated mood after an overnight fast in depression

BackgroundMajor depressive disorder (MDD) comprises subtypes with distinct symptom profiles. For example, patients with melancholic and atypical MDD differ in the direction of appetite and body weight changes as well as mood reactivity. Despite reported links to altered energy metabolism, the role of circulating neuropeptides from the gut in modulating such symptoms remains largely elusive. MethodsWe collected data from 103 participants, including 52 patients with MDD and 51 healthy control participants (HCP). After an overnight fast, we measured plasma levels of (acyl and des-acyl) ghrelin and participants reported their current metabolic and mood states using visual analog scales (VAS). Furthermore, they completed symptom-related questionnaires (i.e., STAI-T). ResultsPatients with atypical versus melancholic MDD reported less negative affect (p = 0.025). Higher levels of acyl ghrelin (corrected for BMI) were associated with improved mood (p = 0.012), specifically in patients with MDD. These associations of ghrelin were not mood-item specific and exceeded correlations with trait markers of negative affectivity. In contrast to associations with mood state, higher levels of ghrelin were not associated with increased hunger per se or changes in appetite in patients with MDD. LimitationsThe study is limited by the cross-sectional design without an intervention. ConclusionsOur results reveal potentially mood-enhancing effects of ghrelin in fasting individuals that exceed associations with metabolic state ratings. These associations with circulating neuropeptides might help explain anti-depressive effects of fasting interventions and could complement conventional treatments in patients with melancholic MDD.

Effects of Iron Deficiency Anemia and its Treatment on Ghrelins, Obestatin and Heat Shock Protein 70

The impact of iron deficiency anemia (IDA) and its treatment on increased levels of heat shock protein 70 (HSP70) in settings with higher tissue stress induced by both ghrelin, which is both an antioxidant and a food intake stimulant, and also obestatin with opposing effects were investigated. The association of pica with these parameters was also examined. The study included 28 patients with IDA and 28 healthy controls. While acyl ve des-acyl ghrelin values were lower (p<0.05) in IDA. With treatment, ghrelin levels climbed. In IDA, obestatin levels were higher than the control values (p<0.05). With the IDA treatment, acyl and des-acyl Ghrelin levels increased. Contrarily, obestatin values fell down. The concentration of HSP 70 in IDA and during its therapy was above control values. Acyl, des-acyl ghrelin, obestatin, and HSP70 levels were increased in the pica group. In the pica group obestatin/acyl ghrelin ratio was comparatively higher (p<0.05). In IDA decrease in ghrelin and an increase in obestatin levels are observed, while HSP 70 remains the same. An increase in the obestatin/acyl ghrelin ratio might be responsible for the pica disorder.

Ghrelin proteolysis increases in plasma of men, but not women, with obesity

AimsSince plasma ghrelin can undergo des-acylation and proteolysis, the aim of this study was to investigate the extent to which an enhancement of these reactions is associated to the decrease of ghrelin in plasma after food intake or in individuals with obesity. Main methodswe performed an intervention cross-sectional study, in which levels of ghrelin, desacyl-ghrelin (DAG), glucose, insulin, ghrelin des-acylation and ghrelin proteolysis were assessed in plasma before and after a test meal in 40 people (n = 21 males) with normal weight (NW, n = 20) or overweight/obesity (OW/OB, n = 20). Key findingsPreprandial ghrelin and DAG levels were lower, whereas preprandial ghrelin proteolysis was ∼4.6-fold higher in plasma of males with OW/OB. In males, ghrelin proteolysis positively correlated with glycemia. Ghrelin and DAG levels were also lower in females with OW/OB, but preprandial ghrelin proteolysis was not different between females with NW or OW/OB. Ghrelin and DAG levels decreased postprandially in males and females, independently of BMI, and ghrelin proteolysis increased postprandially ∼2 folds only in individuals with NW. Ghrelin des-acylation remained unaffected by BMI or feeding status in both sexes. SignificanceCurrent study shows that ghrelin proteolysis increases in males with obesity as well as after meal in lean individuals. Therefore, ghrelin proteolysis may be an important checkpoint and, consequently, a putative pharmacological target to control circulating ghrelin levels in humans.

Relationship Between Acyl and Desacyl Ghrelin Levels with Insulin Resistance and Body Fat Mass in Type 2 Diabetes Mellitus.

PurposeAlthough strong evidence suggests that ghrelin plays an important role in regulating energy balance, the effects of acylated ghrelin (AG) and deacylated ghrelin (DAG) on fat mass are largely undefined. This study aimed to investigate the differential associations of both forms of ghrelin with insulin resistance and body fat mass in patients with type 2 diabetes mellitus (T2DM).Patients and MethodsA total of 162 patients with type 2 diabetes were recruited and classified based on BMI and visceral fat area (VFA) as VFA normal group (n = 78), normal-BMI VFA obesity group (n = 20) and high-BMI VFA obesity group (n = 64). VFA and subcutaneous fat area (SFA) were detected by bioelectrical impedance analysis. Blood samples were collected to measure fasting glucose, insulin, lipids, AG and DAG levels after clinical examination.ResultsCompared with VFA normal group, DAG levels were significantly lower (421.7 ± 106.0 and 388.7 ± 96.5 pg/mL vs 524.4 ± 141.5 pg/mL, P < 0.01) in the two VFA obesity groups. No significant difference was found in AG levels within three groups. Among all subjects, BMI, VFA, SFA, fasting insulin and HOMA-IR were negatively correlated with DAG but positively with AG/DAG ratio (P < 0.01). In contrast, AG was positively correlated with HOMA-IR and fasting glucose (P < 0.01). Multiple stepwise regression analysis showed that fasting glucose was the independent factor of AG, VFA and HOMA-IR were the independent factors related to DAG.ConclusionDAG levels have a strong negative association with excess body fat mass and insulin resistance, whereas AG levels are closely related to elevated blood glucose levels in T2DM patients.

Increased ghrelin and decreased leptin levels in patients with antisocial personality disorder

ObjectiveThe study aimed to compare acyl ghrelin (AG), des-acyl ghrelin (DAG), and leptin levels considered to be used as biological markers in the etiopathogenesis of antisocial personality disorder (ASPD) with healthy controls, and to investigate the relationship between these hormones and aggression and impulsivity. MethodThe study included 45 patients with ASPD and 61 healthy people in the control group. Sociodemographic data form, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Barratt Impulsiveness Scale (BIS-11), and Buss-Durkee Aggression Scale (BDAS) were applied to all participants. Fasting venous blood samples were taken from all participants at the same time of the day and the height and weight of the participants were measured. ResultsIt was found that the mean serum AG and DAG levels were significantly higher than that of healthy controls whereas leptin hormone levels were significantly lower in patients compared to healthy controls. BDI, BAI, BIS-11, and BDAS scores of the patients were significantly higher compared to healthy controls. There was a positive correlation between AG and DAG hormone levels and impulsivity and aggression. DiscussionThe present study is the first in the literature to examine AG, DAG, and leptin hormone levels of patients diagnosed with ASPD. According to the results of the study, it is believed that changes in serum leptin and ghrelin levels will bring a new perspective in terms of understanding the pathophysiological mechanism of ASPD. Further studies are required to explain the definitive roles of these hormones in ASPD.

A Randomized Trial of the Effect of a GnRH Analogue Injection on Ghrelin Levels in Girls

Introduction: Ghrelin concentrations decline during puberty by an unclear mechanism. Acylated ghrelin (AG) is unstable in sampling tubes, but no standardized sampling protocol exists. We hypothesized that ghrelin levels decrease as a consequence of increased gonadotropin-releasing hormone (GnRH) signalling and that the addition of a protease inhibitor to sampling tubes preserves the AG levels. Methods: In this randomized, placebo-controlled, cross-over study, 13 girls with suspected central precocious puberty were included. They performed an adjusted GnRH stimulation test twice and were given Relefact LHRH^® (100 μg/m²) or saline in a randomized order. Blood was sampled repeatedly for 150 min for the analysis of hormone concentrations. Oestradiol levels were only measured at baseline. The protease inhibitor 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) was added to the sampling tubes. Specific ELISA kits were used for the analysis of AG and desacylated ghrelin (DAG) levels. Results: Neither AG nor DAG levels changed after GnRH analogue injection in comparison to saline. The addition of AEBSF preserved AG levels (650.1 ± 257.1 vs. 247.6 ± 123.4 pg/mL, p < 0.001) and decreased DAG levels (51.9 [12.5–115.7] vs. 143.5 [71.4–285.7] pg/mL, p < 0.001). Both AG and DAG levels were inversely associated with insulin levels (r = −0.73, p = 0.005, and r = −0.78, p = 0.002, respectively). AG levels were inversely associated with oestradiol levels (rho = −0.57, p = 0.041). Conclusion: Ghrelin levels do not decrease following a pharmacological dose of a GnRH analogue in the short term in girls. Addition of a protease inhibitor to the sampling tubes decreases AG degradation, resulting in preserved AG and decreased DAG levels.

Nutritional and Anthropometric Indices in Children Receiving Haemodiafiltration vs Conventional Haemodialysis - The HDF, Heart and Height (3H) Study

The "HDF-Heart-Height" study showed that haemodiafiltration (HDF) is associated with improved growth compared to conventional haemodialysis (HD). We report a post-hoc analysis of this study assessing the effect of extracorporeal dialysis therapies on nutritional indices. 107 children were included in the baseline cross-sectional analysis, of whom 79 (43 HD, 36 HDF) completed the 12-month follow-up. Height (Ht), optimal 'dry' weight (Wt), and body mass index (BMI) standard deviations scores (SDS), waist-to-hip ratio, des-acyl ghrelin (DAG), adiponectin, leptin, insulin-like growth factor-1 (IGF-1)-SDS and insulin were measured. The levels of nutritional indices were comparable between HDF and HD patients at baseline and 12-month. On univariable analyses Wt-SDS positively correlated with leptin and IGF-1-SDS, and negatively with DAG, while Ht-SDS of the overall cohort positively correlated with IGF1-SDS and inversely with DAG and adiponectin. On multivariable analyses, higher 12-month Ht-SDS was inversely associated with baseline DAG (beta=-0.13 per 500 higher; 95%CI -0.22, -0.04; P=.004). Higher Wt-SDS at 12-month was positively associated with HDF modality (beta=0.47 vs HD; 95%CI 0.12-0.83; P=.01) and inversely with baseline DAG (beta=-0.18 per 500 higher; 95%CI -0.32, -0.05; P=.006). Growth Hormone (GH) treated patients receiving HDF had higher annualized increase in Ht SDS compared to those on HD. In children on HD and HDF both Wt- and Ht-SDS independently correlated with lower baseline levels of the anorexygenic hormone DAG. HDF may attenuate the resistance to GH, but further studies are required to examine the mechanisms linking HDF to improved growth.

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.

Prospective Evaluation of Ghrelin and Des-Acyl Ghrelin Plasma Levels in Children with Newly Diagnosed Epilepsy: Evidence for Reduced Ghrelin-to-Des-Acyl Ghrelin Ratio in Generalized Epilepsies.

Children with epilepsy and identified as responders to antiseizure medications (ASMs) were found to present markedly higher ghrelin plasma levels when compared to drug-resistant patients. However, it was undetermined if this phenotype could be influenced by the ASMs. Here, we prospectively investigated total ghrelin and des-acyl ghrelin (DAG) plasma levels by enzyme-linked immunosorbent assay before and after ASM administration. Inclusion criteria were: (i) subject with a suspicion of epilepsy; (ii) age ranging from 0 to 16 years; and (iii) informed consent signed by parents or caregivers. Exclusion criteria were acute or chronic metabolic disorders with occasional convulsions but without epilepsy. Fifty patients were followed over a period of one year in Italian neuropediatric centers. Apart from a few exceptions, the majority of children were responsive to ASMs. No differences were found in total ghrelin and DAG levels before and after the treatment, but total ghrelin levels were significantly lower in children with generalized epilepsy compared to those with combined focal and generalized epilepsy. Moreover, the ghrelin-to-DAG ratio was also markedly lower in generalized epilepsies compared to all the other types of epilepsy. Finally, ghrelin was unchanged by ASMs, including the first (e.g., carbamazepine), second (levetiracetam), and third (lacosamide) generation of anticonvulsants.

Circulating acyl and des-acyl ghrelin levels in obese adults: a systematic review and meta-analysis

Ghrelin is the only known orexigenic gut hormone, and its synthesis, secretion and degradation are affected by different metabolic statuses. This meta-analysis aimed to investigate the potential differences in plasma acyl ghrelin (AG) and des-acyl ghrelin (DAG) concentrations between normal weight and obese adults. Systematic literature searches of PubMed, Embase and Web of Science through October 2021 were conducted for articles reporting AG or DAG levels in obesity and normal weight, and 34 studies with 1863 participants who met the eligibility criteria were identified. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated to evaluate group differences in circulating AG and DAG levels. Pooled effect size showed significantly lower levels of baseline AG (SMD: − 0.85; 95% CI: − 1.13 to − 0.57; PSMD < 0.001) and DAG (SMD: − 1.06; 95% CI: − 1.43 to − 0.69; PSMD < 0.001) in obese groups compared with healthy controls, and similar results were observed when subgroup analyses were stratified by the assay technique or storage procedure. Postprandial AG levels in obese subjects were significantly lower than those in controls when stratified by different time points (SMD 30 min: − 0.85, 95% CI: − 1.18 to − 0.53, PSMD < 0.001; SMD 60 min: − 1.00, 95% CI: − 1.37 to − 0.63, PSMD < 0.001; SMD 120 min: − 1.21, 95% CI: − 1.59 to − 0.83, PSMD < 0.001). In healthy subjects, a postprandial decline in AG was observed at 120 min (SMD: − 0.42; 95% CI: − 0.77 to − 0.06; PSMD = 0.021) but not in obese subjects (SMD: − 0.28; 95% CI: − 0.60 to 0.03; PSMD = 0.074). The mean change in AG concentration was similar in both the obese and lean health groups at each time point (ΔSMD30min: 0.31, 95% CI: − 0.35 to 0.97, PSMD = 0.359; ΔSMD60min: 0.17, 95% CI: − 0.12 to 0.46, PSMD = 0.246; ΔSMD120min: 0.21, 95% CI: − 0.13 to 0.54, PSMD = 0.224). This meta-analysis strengthens the clinical evidence supporting the following: lower baseline levels of circulating AG and DAG in obese individuals; declines in postprandial circulating AG levels, both for the healthy and obese individuals; a shorter duration of AG suppression in obese subjects after meal intake. These conclusions have significance for follow-up studies to elucidate the role of various ghrelin forms in energy homeostasis.

The Burden of Peripheral Neuropathy in Nondiabetic Chronic Kidney Disease and the Role of Ghrelin Isoforms in its Development.

Peripheral neuropathy is one of the most common complications in chronic kidney disease (CKD). The neuroprotective role of ghrelin is being explored recently. Here we aim to determine the burden of neuropathy in nondiabetic CKD and to find the association of peripheral nerve function with plasma ghrelin levels in these patients. This was a cross-sectional study conducted in nondiabetic CKD patients on conservative management to determine the magnitude of neuropathy. The association of ghrelin isoforms with nerve functions was assessed between three groups, namely CKD with neuropathy, CKD without neuropathy, and healthy volunteers, with 20 participants in each group. The proportion of neuropathy in nondiabetic CKD was 78% (n = 78), of which 51% (n = 40) were asymptomatic. Des acyl ghrelin (DAG) and total ghrelin (TG) levels were 1545.5 ± 487.4 and 1567.4 ± 485.3 pg/mL, respectively, in CKD patients with neuropathy and were found to be elevated compared to those without neuropathy, who had 1000.4 ± 264.2 and 1019.7 ± 264.3 pg/mL of DAG and TG, respectively (P < 0.001). Assessment of correlation between nerve conduction parameters and DAG levels showed positive correlation between DAG levels and common peroneal latency (r = 0.69; P < 0.01), median sensory latency (r = 0.45; P < 0.05), and sural latency (r = 0.51; P < 0.05). We found negative correlation between median velocity (r =-0.56; P < 0.05), common peroneal velocity (r = -0.64; P < 0.01), median sensory velocity (r =-0.49; P < 0.05), and sural velocity (r = -0.54; P < 0.05). There was no statistically significant difference in acyl ghrelin levels among the groups. The prevalence of peripheral neuropathy in CKD is significantly higher with almost half of them being asymptomatic. Impaired renal clearance in CKD leads to the accumulation of DAG, which subsequently inhibits the neuroprotective functions of AG leading to neuropathy in CKD.

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

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

Acylated Ghrelin Attenuates l-Thyroxin-induced Cardiac Damage in Rats by Antioxidant and Anti-inflammatory Effects and Downregulating Components of the Cardiac Renin-angiotensin System.

This study investigated the protective effect of acylated ghrelin (AG) against l-thyroxin (l-Thy)-induced cardiac damage in rats and examined possible mechanisms. Male rats were divided into five intervention groups of 12 rats/group: control, control + AG, l-Thy, l-Thy + AG, and l-Thy + AG + [D-Lys3]-GHRP-6 (AG antagonist). l-Thy significantly reduced the levels of AG and des-acyl ghrelin and the AG to des-acyl ghrelin ratio. Administration of AG to l-Thy-treated rats reduced cardiac weights and levels of reactive oxygen species and preserved the function and structure of the left ventricle. In addition, AG also reduced the protein levels of cleaved caspase-3 and cytochrome c and prevented mitochondrial permeability transition pore opening. In the left ventricle of both control + AG-treated and l-Thy + AG-treated rats, AG significantly increased left ventricular levels of manganese superoxide dismutase (SOD2), total glutathione (GSH), and Bcl2. It also reduced the levels of malondialdehyde, tumor necrosis factor-α (TNF-α), interleukin-6, and Bax and the nuclear activity of nuclear factor-kappa B. Concomitantly, in both treated groups, AG reduced the mRNA and protein levels of NADPH oxidase 1, angiotensin (Ang) II type 1 receptor, and Ang-converting enzyme 2. All the beneficial effects of AG in l-Thy-treated rats were prevented by the coadministration of [D-Lys3]-GHRP-6, a selective growth hormone secretagogue receptor subtype 1a antagonist. In conclusion, AG protects against hyperthyroidism-induced cardiac hypertrophy and damage, which is mainly due to its antioxidant and anti-inflammatory potentials and requires the activation of GHS-R1a.

Ghrelin after chemotherapy as a prognostic predictor of progression-free survival in patients with muscle-invasive bladder cancer.

BackgroundAlthough the patients with muscle-invasive bladder cancer (MIBC) generally have poor prognosis, the utility of these biomarkers for the prediction of oncological outcomes in MIBC has not been completely explored. Ghrelin regulates processes associated with cancer, including cell proliferation, apoptosis, cell migration, cell invasion, and angiogenesis. Thus, we aimed to evaluate the impact of serum ghrelin levels on survival in MIBC.MethodsIn this study, we reviewed the clinical and pathological records of 56 patients who were diagnosed with MIBC between November 2015 and November 2019 at Gifu and Hirosaki University Hospitals. We focused on 27 patients who had received chemotherapy and collected blood samples before and after chemotherapy. Blood samples were collected before chemotherapy and after completing two cycles of chemotherapy. Serum acyl (AG) and desacyl ghrelin (DG) were measured using AG and DG enzyme-linked immunosorbent assay kits (SCETI, Tokyo, Japan), respectively.ResultsThe 3-year overall and progression-free survival (PFS) rates were 82.9% and 68.3%, respectively. According to the AG level after chemotherapy, the 3-year PFS rates were 77.5% and 53.0% in patients with AG levels ≥1.34 and <1.34 pg/mL, respectively (P=0.038). With regard to DG levels after chemotherapy, the 3-year PFS rates were 90.9% and 43.3% in patients with DG levels <92.3 and ≥92.3 pg/mL, respectively (P=0.039). On multivariate analysis, serum AG levels were significantly associated with PFS.ConclusionsThis study suggested the usefulness of the ghrelin as a prognostic predictor of PFS in patients with MIBC.

Importance of plasma ghrelin levels with special reference to nutritional metabolism and energy expenditure in pediatric patients with severe motor and intellectual disabilities.

Nutritional metabolism is complex in pediatric patients with severe motor and intellectual disability (SMID), and therefore, appropriate estimation of the energy requirements is difficult. Focusing on ghrelin's role in energy metabolism regulation, we investigated plasma ghrelin levels in pediatric SMID patients and analyzed its nutritional significance as a regulatory marker of energy reserve. Fasting plasma total, acyl, and des-acyl ghrelin levels in 40 patients with SMID, including cerebral palsy (CP) (n=20) and muscular disease (MD) (n=8), and healthy controls (n=13) were investigated. The correlations of plasma ghrelin levels with anthropometry, blood nutritional markers, energy intake, and resting energy expenditure (REE) measured with indirect calorimetry were analyzed. A p value<0.05 was considered significant. SMID patients had significantly higher acyl ghrelin, and lower body mass index (BMI), z-scores of body weight (BW), body height and BMI, and albumin than controls. CP patients had significantly higher total and acyl ghrelin, z-score of the mid-upper arm circumference (MUAC), retinol-binding protein, transthyretin, creatinine, and glucose than MD patients. Total and acyl ghrelin in CP patients and des-acyl ghrelin in MD patients had significant negative correlations with MUAC and upper arm fat area. In CP patients, total and acyl ghrelin had significant positive correlations with REE/BW (kcal/kg), and total ghrelin was predictive of REE/BW (r2=0.625, p<0.0001). An increase in acyl ghrelin observed in SMID patients possibly indicates energy reserve deficiency. In CP patients, total and acyl ghrelin inversely reflected total body fat mass, resulting in strongly positive correlations with REE/BW. The measurement of plasma ghrelin may be useful to assess nutritional metabolism and energy reserve in pediatric SMID patients, such as CP and MD patients.

Quantitative and Topographic Analysis by Immunohistochemical Expression of Ghrelin Gastric Cells in Patients with Morbid Obesity.

PurposeThe cellular distribution of ghrelin positive cells is not well defined. The aim of the study is to quantify and determine the distribution of ghrelin cells in gastric mucosa in patients with morbid obesity and relate this finding to gender, comorbidities, gastritis, and plasmatic levels of acyl and desacylghrelin before and after laparoscopic sleeve gastrectomy.Patient and MethodsWe performed a study on 61 patients with BMI≥50 kg/m2 operated by laparoscopic sleeve gastrectomy. Three gastric regions were analyzed by histopathology and immunohistology. Blood sample was taken before surgery, and at 6 and 12 months post-surgery, to study the plasma levels of ghrelin isoforms.ResultsGhrelin cells are present in all regions of the gastric mucosa, with a greater number in the body and the fundus. Difference was found in the antrum between male and female patients (p=0.018). Patients with arterial hypertension also showed a lower level of cells in antrum (p<0.05). Acylghrelin levels after surgery were significantly lower (32.83+5.6 pg/mL to 10.09+11.8 pg/mL, p<0.05). Values of desacylghrelin tended to decrease but no significant variation was observed (207.4+39.3 pg/mL to 188.84+52.3 pg/mL).ConclusionOur patients show ghrelin cells in all areas of the stomach. Gender, comorbidities, and gastritis are determinant on gastric ghrelin-producing cells distribution.

Influence of endurance training-induced weight loss on the levels of ghrelin and obestatin of obese women with polycystic ovary syndrome

Polycystic ovary syndrome is an observed plurimetabolic syndrome associated with central obesity and insulin resistance. The purpose of the present study was to investigate the effects of 12-week training program on weight loss, serum ghrelin, acylated ghrelin, des-acylated ghrelin, and obestatin levels in obese sedentary women with polycystic ovary syndrome (PCOS). To this end, thirty sedentary obese women with PCOS (mean age 31.07 ± 2.49 years, height 162.23 ± 2.39 cm, weight: 87.23 ± 4.48 kg, BMI 33.12 ± 0.92) were recruited from a multidisciplinary PCOS specialty clinic in Tabriz city in 2017 and evaluated before and after a 12-week training program, including 45 min per session of aerobic training at an intensity of 60–75% of age-predicted maximum heart rate (300 kcal/day). After the exercise program, body weight, waist circumference, and percentage body fat mass were decreased. Also, fasting glucose, insulin, and serum acylated ghrelin levels were significantly decreased (P 0.05). The moderate aerobic exercise training is associated with improvements in obestatin and health profiles of obese women with PCOS without associated structured energy restriction.

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

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