Des-acyl Ghrelin Research Articles

Short term changes in des-acyl ghrelin following bariatric surgery

Short term changes in des-acyl ghrelin following bariatric surgery

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.

Exploring the role of ghrelin and des-acyl ghrelin in chemotherapy-induced nausea and vomiting

Ghrelin and its mimetics have been shown to reduce cisplatin-induced emesis in preclinical studies using ferrets and shrews. This study investigated the effectiveness of ghrelin and des-acyl ghrelin (DAG) in antagonizing cisplatin-induced emesis and physiological changes indicative of nausea in Suncus murinus. Animals implanted with radiotelemetry devices were administered ghrelin (0.2, 1.0, and 5.0 μg/day), DAG (0.2, 1.0, and 5.0 μg/day), or saline (14 μL/day) intracerebroventricularly 4 days before and 3 days after treatment with cisplatin (30 mg/kg). At the end, the anti-apoptotic potentials of ghrelin and DAG were assessed by measuring Bax expression and cytochrome C activity. Neurotransmitter changes in the brain were evaluated using liquid chromatography–mass spectrometry analysis. Ghrelin and DAG reduced cisplatin-induced emesis in the delayed (24–72 h) but not the acute phase (0–24 h) of emesis. Ghrelin also partially reversed the inhibitory effects of cisplatin on food intake without affecting gastrointestinal myoelectrical activity or causing hypothermia; however, ghrelin or DAG did not prevent these effects. Ghrelin and DAG could attenuate the cisplatin-induced upregulation of Bax and cytochrome C in the ileum. Cisplatin dysregulated neurotransmitter levels in the frontal cortex, amygdala, thalamus, hypothalamus, and brainstem, and this was partially restored by low doses of ghrelin and DAG. Our findings suggest that ghrelin and DAG exhibit protective effects against cisplatin-induced delayed emesis. The underlying antiemetic mechanism may involve GHSR and/or unspecified pathways that modulate the neurotransmitters involved in emesis control in the brain and an action to attenuate apoptosis in the gastrointestinal tract.

The New Trends in Physiological and Pathological Actions of Ghrelin (Brain-Heart Axis) on the Heart and Cardiovascular System

Background: Ghrelin increased significantly the Left Ventriculus Eject Fraction and end-systolic volume after 30 minutes of intra-venous injection and without alterations heart rate and blood pressure. Ghrelin was discovered in 1999 as an only one 28 amino acid peptides (with octanoyl serine group) located on the short arm of chromosome 3 (position 3p25-26) having six exons, two are noncoding and four introns and encodes a 511 bp mRNA. Ghrelin is synthesized by the endocrine X/A-like cells located from the gastric fundus mucosa through the whole mucosa of the medium right vertical side of the stomach until to the 1 inch before anatomical pylorus. These cells are responsible to produced 80% of the whole ghrelin produced in the human body. Furthermore, other place of this production occurs at the hypothalamus, the pituitary, second portion of duodenum, pancreas, heart and other tissues. Bibliographic references also demonstrate the importance of ghrelin’s action in the main cardiovascular activities. Related to cardiovascular activities, ghrelin plays multitudinous beneficial and thereby help during cardiovascular diseases. Several studies demonstrated that ghrelin cause an anti-inflammatory activity by the inhibition of proinflammatory cytokines which can diminish inflammatory diseases in the heart, pericardium and specific innervations, for instance, vagus nerve and inhibited sympathetic nerves. Outcomes of this review emphasize these important actions of ghrelin. Methods: A systematic review of ghrelin activities over the heart and cardiovascular system with the inclusion of papers in review involved the physiological and physio pathological activities of ghrelin in vivo and in vitro studies. Results: Ghrelin is a natural tide with the growth hormone secretagogue (GHS) receptor (GHS-R) which cloned in 1996. The processes which generate this peptide and ghrelin-related peptides are transcriptional, translational and posttranslational. Homo and heterodimers of GHS-R and other yet unidentified receptors mediate the biological actions of acyl ghrelin and desacyl ghrelin. However, the main biological functions of ghrelin involve the secretion of growth hormone, stimulation of appetite and food intake at the hypothalamus, modulate acid secretion and motility, endocrine and exocrine pancreas secretion, blockaded insulin activity, heart functions and cardiovascular responses and other. Conclusion: One of the main occurrences in acute heart infarction is an increase activation of cardiac sympathetic nerve activity (CSNA) which is one of the causes of chronic cardiac dysfunction (CCD). Ghrelin is an effective for obtain a better cardiac function and by the suppression of renal sympathetic nerve activity which also have an important benefit to the acute myocardial infarction. Therefore, the physiological effects of ghrelin are very important to the body homeostasis even in the grave heart and cardiovascular diseases and in the immunological system.

Acute effects of exercise intensity on butyrylcholinesterase and ghrelin in young men: A randomized controlled study

Background/objectivesButyrylcholinesterase (BChE), a liver-derived enzyme that hydrolyzes acylated ghrelin to des-acylated ghrelin, may trigger a potential mechanism responsible for the acute exercise-induced suppression of acylated ghrelin. However, studies examining the effects of an acute bout of high-intensity exercise on BChE and acylated ghrelin have yielded inconsistent findings. This study aimed to examine the acute effects of exercise intensity on BChE, acylated ghrelin and des-acylated ghrelin concentrations in humans. MethodsFifteen young men (aged 22.7 ± 1.8 years, mean ± standard deviation) completed three, half-day laboratory-based trials (i.e., high-intensity exercise, low-intensity exercise and control), in a random order. In the exercise trials, the participants ran for 60 min (from 09:30 to 10:30) at a speed eliciting 70 % (high-intensity) or 40 % (low-intensity) of their maximum oxygen uptake and then rested for 90 min. In the control trial, participants sat on a chair for the entire trial (from 09:30 to 12:00). Venous blood samples were collected at 09:30, 10:00, 10:30, 11:00, 11:30 and 12:00. ResultsThe BChE concentration was not altered over time among the three trials. Total acylated and des-acylated ghrelin area under the curve during the first 60 min (i.e., from 0 min to 60 min) of the main trial were lower in the high-intensity exercise trial than in the control (acylated ghrelin, mean difference: 62.6 pg/mL, p < 0.001; des-acylated ghrelin, mean difference: 31.4 pg/mL, p = 0.035) and the low-intensity exercise trial (acylated ghrelin, mean difference: 87.7 pg/mL, p < 0.001; des-acylated ghrelin, mean difference: 43.0 pg/mL, p = 0.042). ConclusionThe findings suggest that BChE may not be involved in the modulation of ghrelin even though lowered acylated ghrelin concentration was observed after high-intensity exercise.

Desacylghrelin modulates GHS-R1 receptor expression and cell differentiation in placental BeWo cells

Backgroundand purpose: Ghrelin is the endogenous ligand of the growth hormone secretagogue receptor (GHS-R1). Ghrelin, and GHS-R1, may have a role in placental growth and function, and its unacylated form desacylghrelin (DAG) could be involved in fetal growth. Nevertheless, the effects of DAG on placental function, and the receptor involved in its actions, remain to be determined. We aimed to investigate the effect of DAG in placental BeWo cells viability, proliferation, differentiation, and GSH-R1 expression. MethodsBeWo cells, a human trophoblast cell line, was cultured with 3 nM DAG during 12, 24, 48, and 72 h. Cell viability, proliferation, differentiation (assessed by human Chorionic Gonadotropin quantification), and GSH-R1 expression were analyzed. To evaluate the mechanism of DAG effect on GSH-R1, 30 nM receptor antagonist ([D-Lys3]-GHRP-6) was added alone or in combination with 3 nM DAG during 12 h and 24 h. ResultsDAG has no effect on cell proliferation or viability, but it has an inhibitory effect on cell differentiation. DAG had a stimulatory effect on GSH-R1 expression at 12 and 24 h (p = 0.029 and p = 0.025, respectively). On the contrary, culture with 48 h DAG inhibits GSH-R1 expression compared to the control (p = 0.005), while GSH-R1 antagonist inhibited the effect of DAG on GSH-R1 expression. DAG also reduces intracellular (p = 0.020) and secreted (p = 0.011) hCG concentration in BeWo cells. ConclusionDAG increases GHS-R1 expression, potentially mediated through GHS-R1 itself. DAG may also inhibit placental BeWo cell differentiation, suggesting a possible role of DAG in placental and fetal physiology.

Measurement of Ghrelin as a Marker of Appetite Dysregulation in Cats with and without Chronic Kidney Disease.

Appetite abnormalities and weight loss are important comorbidities in the treatment of chronic kidney disease (CKD) in cats. Ghrelin, a key hormone involved in the regulation of appetite and metabolism, is a potential marker of appetite dysregulation in cats with CKD. The aim of this study was to compare the plasma concentrations of acylated, desacyl, and total ghrelin in normal cats and cats with CKD. Storage methodology was investigated prior to evaluating ghrelin concentrations in normal and CKD cats to facilitate clinical sample collection. Twelve normal cats and twelve cats with CKD were enrolled. Plasma acylated and total ghrelin concentrations were measured using radioimmunoassay. Desacyl ghrelin was calculated (total ghrelin minus acylated ghrelin). Cats with CKD had significantly increased total ghrelin and calculated desacyl ghrelin concentrations in comparison to normal cats (p < 0.0001 and p = 0.0001). There was no significant difference in active ghrelin concentrations between groups. Both total ghrelin and calculated desacyl ghrelin were significantly correlated with serum creatinine concentrations (p < 0.0001, r = 0.70 and p < 0.0001, r = 0.73). Elevated plasma desacyl ghrelin concentrations in cats with CKD provides evidence for dysregulation of appetite in feline CKD.

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&lt;0.05) in IDA. With treatment, ghrelin levels climbed. In IDA, obestatin levels were higher than the control values (p&lt;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&lt;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.

Relation of Aortic Waveforms with Gut Hormones following Continuous and Interval Exercise among Older Adults with Prediabetes.

Prediabetes raises cardiovascular disease risk, in part through elevated aortic waveforms. While insulin is a vasodilatory hormone, the gut hormone relation to aortic waveforms is less clear. We hypothesized that exercise, independent of intensity, would favor aortic waveforms in relation to gut hormones. Older adults (61.3 ± 1.5 yr; 33.2 ± 1.1 kg/m2) with prediabetes (ADA criteria) were randomized to undertake 60 min of work-matched continuous (CONT, n = 14) or interval (INT, n = 14) exercise for 2 wks. During a 180 min 75-g OGTT, a number of aortic waveforms (applanation tonometry) were assessed: the augmentation pressure (AP) and index (AIx75), brachial (bBP) and central blood pressure (cBP), pulse pressure (bPP and cPP), pulse pressure amplification (PPA), and forward (Pf) and backward pressure (Pb) waveforms. Acylated-ghrelin (AG), des-acylated ghrelin (dAG), GIP, and GLP-1active were measured, and correlations were co-varied for insulin. Independent of intensity, exercise increased VO2peak (p = 0.01) and PPA120min (p = 0.01) and reduced weight (p < 0.01), as well as AP120min (p = 0.02) and AIx75120min (p < 0.01). CONT lowered bSBP (p < 0.02) and bDBP (p < 0.02) tAUC180min more than INT. There were decreases dAG0min related to Pb120min (r = 0.47, p = 0.03), cPP120min (r = 0.48, p = 0.02), and AP120min (r = 0.46, p = 0.02). Declines in AG tAUC60min correlated with lower Pb120min (r = 0.47, p = 0.03) and cPP120min (r = 0.49, p = 0.02) were also found. GLP-1active 0min was reduced associated with lowered AP180min (r = 0.49, p = 0.02). Thus, while CONT exercise favored blood pressure, both intensities of exercise improved aortic waveforms in relation to gut hormones after controlling for insulin.

Liver-Expressed Antimicrobial Peptide 2 Is a Hepatokine That Predicts Weight Loss and Complete Remission of Type 2 Diabetes Mellitus after Vertical Sleeve Gastrectomy in Japanese Individuals

Introduction: Vertical sleeve gastrectomy (VSG) is considered one of the most effective treatments for sustained weight loss and complete remission of type 2 diabetes mellitus (CR-T2DM). Liver-expressed antimicrobial peptide 2 (LEAP2), a ghrelin receptor antagonist peptide, is a metabolic hormone regulated by VSG. However, it is unknown whether LEAP2 can be used to predict the outcomes of VSG. This study aimed to evaluate LEAP2 as a predictive factor for weight loss and CR-T2DM after VSG. Methods: This retrospective study included 39 Japanese participants with obesity who underwent VSG. Serum LEAP2, des-acyl ghrelin (DAG), and other metabolic and anthropometric parameters were studied before and at 12 months after VSG. Receiver operating characteristics (ROC) curve was generated to evaluate predictive score for weight loss with cut-off value of >50 percent excess weight loss. ROC curve was also generated to assess CR-T2DM. Results: Serum LEAP2 levels were significantly higher in participants with body mass index (BMI) 32–50 kg/m² than in those with normal weight. Participants with BMI >50 kg/m² had lower serum LEAP2 concentrations than those with BMI 32–50 kg/m². VSG caused a significant reduction in serum DAG concentrations, but it did not affect serum LEAP2 concentrations in either male or female participants. Preoperative serum LEAP2 concentration of 2.88 pmol/mL was the optimal cutoff value for predicting weight loss after VSG, with sensitivity of 80.0% and specificity of 75.9%. Preoperative serum LEAP2 level higher than 4.67 pmol/mL predicted CR-T2DM after VSG with sensitivity of 100% and specificity of 58.8%. Conclusion: Preoperative serum LEAP2 could predict weight loss and CR-T2DM as outcomes of VSG.

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.

Involvement of ghrelin in the regulation of swallowing motor activity in an arterially perfused rat preparation

Ghrelin, a peripheral peptide produced in the stomach, is involved in the neural networks that control food intake. Alterations in motor components, such as swallowing, are believed to be significant in the regulation food intake by orexigenic signals. However, there has been no detailed investigation of the relationship between ghrelin and swallowing activities induced in motor nerves innervating the pharyngeal and laryngeal muscles. In this study, we examined the effects of ghrelin administration on swallowing motor activity in arterially perfused rats. Injection of distilled water (0.5 ml) into the oral cavity or electrical stimulation of the superior laryngeal nerve evoked swallowing motor activity in the cervical vagus nerve. Administration of ghrelin (6 nM), but not des-acylated ghrelin (6 nM), into the perfusate increased the peak burst amplitude and burst duration, and shortened the first burst interval of water injection-induced swallowing. These ghrelin-induced changes in swallowing motor activity were blocked by the administration of JMV2959 (6 µM), a growth hormone secretagogue receptor antagonist. In preparations in which the hypothalamus was removed, ghrelin had no effect on swallowing motor activity. Furthermore, ghrelin-induced changes were counteracted by the administration of BIBO3304 (1 µM) or L-152,804 (1 µM), antagonists of neuropeptide Y Y1 and Y5 receptors, respectively, which are essential for ghrelin-induced enhancement of food intake. Ghrelin also increased the peak burst amplitude and burst duration of the swallowing motor activity evoked by electrical stimulation of the superior laryngeal nerve, although the effects of ghrelin on the number of swallowing bursts and burst intervals varied with stimulus intensity. These results suggest that ghrelin enhances the magnitude and frequency of bursts of swallowing motor activity by acting via the hypothalamic neural network, and that neuropeptide Y Y1 and Y5 receptors are involved in this enhancement.

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.

Ghrelin, growth hormone and insulin-like growth Factor-I levels in people with protein C deficiency

The primary objective of this study was to examine if people with protein C deficiency, which is a natural anticoagulant and also an endogenous acyl ghrelin peptidase, have elevated circulating levels of acyl ghrelin. The clinical trial was conducted in a university hospital setting. People with protein C deficiency were identified and invited to participate by a specialized coagulation outpatient clinic. People with protein C deficiency were examined and compared to age, sex, and body mass index matched healthy controls with regards to acyl ghrelin, unacylated ghrelin, growth hormone (GH) and insulin-like growth-factor I (IGF-I) in a cross-sectional case-control study. Systemic levels of acyl ghrelin, desacyl ghrelin, acyl-to-desacyl ghrelin ratio, GH and IGF-I were similar in people with protein C deficiency and healthy controls. Despite a significant reduction of protein C in people with protein C deficiency, there was no difference in acyl ghrelin or the secondary end points unacylated ghrelin, GH, or IGF-I in people with protein C deficiency.

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.

Acylated ghrelin suppresses doxorubicin-induced testicular damage and improves sperm parameters in rats via activation of Nrf2 and mammalian target of rapamycin.

Exogenous administration of acylated ghrelin (AG) afforded reproductive protective effect in several animal models but not in those treated with doxorubicin (DOX). This study evaluated the protective effect of AG against DOX-induced testicular damage and impairment in sperm parameters in rats and examined the potential mechanisms of action. Adult male rats were divided into five groups (n = 8/each) as control, control + AG (40 nmol/kg/day; subcutaneous), DOX (10 mg/kg/day 1; intraperitoneal [i.p.]), DOX + AG, and DOX + AG + brusatol (an Nrf2 inhibitor) (2 mg/kg/every 3 days; i.p.). The treatment regimen continued for 65 days. AG prevented testicular damage and apoptosis; increased sperm count, motility, and viability; and reduced the number of abnormal sperms. It also increased their circulatory levels of AG, des-acylated ghrelin (DAG), and AG/DAG ratio and the testicular mRNA levels of ghrelin and growth hormone secretagogue receptor 1a Concomitantly, AG increased serum and testicular testosterone levels, reduced serum levels of the follicle-stimulating hormone and luteinizing hormone, and upregulated the testicular protein levels of the steroidogenic acute regulatory protein and 3β-hydroxysteroid dehydrogenase in DOX-treated rats. In the testes of the control and DOX-treated rats, AG increased the phosphorylation of mammalian target of rapamycin and stimulated the levels of glutathione and superoxide dismutase, as well as the nuclear activation of Nrf2. All these effects were completely prevented by co-treatment with brusatol. AG replacement therapy could be a novel strategy to prevent reproductive toxicity in cancer patients.