Peptide Ghrelin Research Articles

Anti-hypothalamus autoantibodies in anorexia nervosa: a possible new mechanism in neuro-physiological derangement?

PurposeAnorexia nervosa (AN) is a serious and complex mental disorder affecting mainly young adult women. AN patients are characterized by low body weight in combination with self-induced starvation, intense fear of gaining weight, and distortion of body image. AN is a multifactorial disease, linked by recent evidence to a dysregulation of the immune system.MethodsIn this pilot study, 22 blood serums from AN patients were tested for the presence of autoantibodies against primate hypothalamic periventricular neurons by immunofluorescence and by a home-made ELISA assay. Cellular fluorescence suggests the presence of autoantibodies which are able to recognize these neurons (both to body cell and fiber levels). By means of ELISA, these autoantibodies are quantitatively evaluated. In addition, orexigenic and anorexigenic molecules were measured by ELISA. As control, 18 blood serums from healthy age matched woman were analysed.ResultsAll AN patients showed a reactivity against hypothalamic neurons both by immunofluorescence and ELISA. In addition, ghrelin, pro-opiomelanocortin (POMC), and agouti-related peptide (AGRP) were significantly higher than in control serums (p < 0.0001). In contrast, leptin was significantly lower in AN patients than controls (p < 0.0001).ConclusionsImmunoreaction and ELISA assays on AN blood serum suggest the presence of autoantibodies AN related. However, it is not easy to determine the action of these antibodies in vivo: they could interact with specific ligands expressed by hypothalamic cells preventing their physiological role, however, it is also possible that they could induce an aspecific stimulation in the target cells leading to an increased secretion of anorexigenic molecules. Further studies are needed to fully understand the involvement of the immune system in AN pathogenesis.Level of evidenceV, descriptive study.

Effects of mindset on hormonal responding, neural representations, subjective experience and intake

A person can alternate between food-related mindsets, which in turn may depend on one's emotional state or situation. Being in a certain mindset can influence food-related thoughts, but interestingly it might also affect eating-related physiological responses. The current study investigates the influence of an induced ‘loss of control’ mindset as compared to an ‘in control’ mindset on hormonal, neural and behavioural responses to chocolate stimuli. Mindsets were induced by having female chocolate lovers view a short movie during two sessions in a within-subjects design. Neural responses to visual chocolate stimuli were measured using an ultra-high field (7T) scanner. Momentary ghrelin and glucagon-like peptide 1 (GLP-1) levels were determined on five moments and were simultaneously assessed with self-reports on perceptions of chocolate craving, hunger and feelings of control. Furthermore, chocolate intake was measured using a bogus chocolate taste test. It was hypothesized that the loss of control mindset would lead to hormonal, neural and behavioural responses that prepare for ongoing food intake, even after eating, while the control mindset would lead to responses reflecting satiety. Results show that neural activity in the mesocorticolimbic system was stronger for chocolate stimuli than for neutral stimuli and that ghrelin and GLP-1 levels responded to food intake, irrespective of mindset. Self-reported craving and actual chocolate intake were affected by mindset, in that cravings and intake were higher with a loss of control mindset than with a control mindset. Interestingly, these findings suggest that physiology on the one hand (hormonal and neural responses) and behavior and subjective experience (food intake and craving) on the other hand are not in sync, are not equally affected by mindset.

The relationship between ghrelin and inflammation in diabetic rat stomach

Ghrelin is a hormone that regulates the digestive system, as well as has immunomodulating effects. The aim of this study is to explain effects of ghrelin on inflammation and oxidative stress parameters in the stomach. Male Sprague Dawley rats 8-10 weeks old (n = 21) were randomly divided into three groups as control, type 2 diabetes (T2DM) and diabetes and given exogenous ghrelin (T2DM+Gh). The daily feed and water intake of the animals were measured. The levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), and interleukin-10 (IL-10) mRNA in tissues were analyzed using RT-PCR technique. Ghrelin and nuclear factor-κβ (NF-κβ) peptides were detected by immunohistochemistry. T2DM group had a significant increase in water intake when compared to control group. T2DM group had significantly higher levels of IL-6, IL-1, and IL-10 mRNA expression than control group. IL-1β and IL-10 mRNA expression were significantly lower in T2DM+Gh group than in T2DM group. In T2DM group, NF-κβ was higher than in control group, but it was lower in T2DM+Gh group. In terms of oxidative stress, there were non-significant changes. According to our findings, exogenous ghrelin intake was found to be highly effective in reducing inflammation in stomach tissue with type 2 diabetes (Tab. 1, Fig. 3, Ref. 33). Text in PDF www.elis.sk Keywords: ghrelin, rat, type 2 diabetes, stomach, inflammation.

Ameliorative Effect of Ghrelin on Thyroxin Hormones and Body Weight in Hyperthyroidism Male rats

The study's objective is to evaluate the enhanced effect of the ghrelin on the body weight and thyroid hormones in male rats after inducing hyperthyroidism by L–thyroxin. The rats (95 males) were split into two groups. The first group consisted of 25 male rats that were given normal saline for 30 days S.C and set as a control group. While the remainder of the animals were given levothyroxine 500g/kg subcutaneously for 30 days to induce hyperthyroidism. after induction the divided into 4 groups as followe ,the first one was the control group that mentioned previously, the second group was male rats were given normal saline for 30 days S.C, the third group was male rats were given ghrelin at a dose of (0.5nmol/100μl saline) for 30 days S.C, and the fourth group was male rats (1nmol/100μl saline) for 30 days S.C. The fifth group consisted of hyperthyroidism male rats that was given ghrelin at a dosage of (2nmol/100μl saline) for 30 days S.C. The results of final weight and weight gain are presented showed no significant difference in initial weight within all groups that were observed, while a significant decrease in final body weight in hyperthyroidism group compared with control group. On the other hand, the results revealed a significant decrease in body weight gain in male rats have hyperthyroidism compared with the control group. While the results observed a significant increase final body weight and body weight gain in all treated rats with ghrelin as compared with hyperthyroidism group. On other hand, the effect of hyperthyroidism on serum TSH, T3, and T4 concentrations revealed that the hyperthyroidism group had a significant rise in serum T3 and T4 concentrations when compared to the control group. While no significant drop in serum TSH concentration was observed in all hyperthyroidism groups handled with ghrelin (0.5, 1 and 2 nmol) as compared to the hyperthyroidism group, a significant decrease in serum T3 and T4 level was observed in all hyperthyroidism groups treated with ghrelin in comparison to the group of hyperthyroidism. Ghrelin peptide hormone and it has been shown to have potential effects on the body weight and thyroid hormone.

Ghrelin Enhancer, the Latest Evidence of Rikkunshito.

Rikkunshito is a Japanese herbal medicine (Kampo) that has been attracting attention and researched by many researchers not only in Japan but also worldwide. There are 214 rikkunshito articles that can be searched on PubMed by August 2021. The reason why rikkunshito has attracted so much attention is due to an epoch-making report (Gastroenterology, 2008) discovered that rikkunshito promotes the secretion of the orexigenic peptide ghrelin. Since then, many researchers have discovered that rikkunshito has a direct effect on the ghrelin receptor, GHS-R1a, and an effect of enhancing the ghrelin signal to the brain. Additionally, a lot of evidence that rikkunshito is expected to be effective for various gastrointestinal diseases have also been demonstrated. Numerous basic and clinical studies have suggested that rikkunshito affects (i) various discomforts caused by anticancer drugs, gastroesophageal reflux disease, functional dyspepsia, (ii) various stress-induced anorexia, (iii) hypophagia in the elderly, and (iv) healthy lifespan. In this review, as one who discovered the ghrelin enhancer effect of rikkunshito, we will review the research of rikkunshito so far and report on the latest research results.

Metabolic profiles, energy expenditures, and body compositions of the weight regain versus sustained weight loss patients who underwent Roux-en-Y gastric bypass.

Weight regain (WR) has been an emerging problem after Roux-en Y gastric bypass (RYGB) and little is known about the mechanisms of WR after RYGB. To evaluate the mechanisms of WR after RYGB through the postprandial gut hormones response, particularly glucagon-like peptide-1 (GLP-1), which regulates appetite control, energy expenditure, body composition, physical activities, dietary intake, and psychological factors. Duke University Medical Center, Durham, North Carolina. A cross sectional study of 34 patients who underwent RYGB at least 2 years and achieved ≥50% of excess weight loss at 1year was conducted. The subjects were categorized into WR group or sustained weight loss group, based upon whether their WR was ≥15% of postoperative lowest weight. The WR group had less augmented postprandial GLP-1 response but exaggerated hyperinsulinemia. Postprandial peptide YY, ghrelin, and glucose were not different between group. Patients who regained weight required less weight-adjusted energy expenditure and had more percentage body fat and less percentage lean mass. The caloric intake and diet composition were comparable between groups; however, the WR group had higher depression scores, binge eating scales, and hunger rating and spent significantly less time on vigorous exercise. The mechanisms of WR in patients who were initially successful after RYGB are complex and involved not only the role of postprandial gut hormone response but are also related to energy expenditure adaptation and body composition changes. Moreover, food preference and physical activity may play roles in weight control after bariatric surgery. Further prospective controlled trial is needed to explore the mechanisms of WR.

Involvement of Ghrelin Dynamics in Stress-Induced Eating Disorder: Effects of Sex and Aging.

Stress, a factor that affects appetite in our daily lives, enhances or suppresses appetite and changes palatability. However, so far, the mechanisms underlying the link between stress and eating have not been fully elucidated. Among the peripherally produced appetite-related peptides, ghrelin is the only orexigenic peptide, and abnormalities in the dynamics and reactivity of this peptide are involved in appetite abnormalities in various diseases and psychological states. This review presents an overview of the research results of studies evaluating the effects of various stresses on appetite. The first half of this review describes the relationship between appetite and stress, and the second half describes the relationship between the appetite-promoting peptide ghrelin and stress. The effects of sex differences and aging under stress on appetite are also described.

Nanosecond pulsed electric fields prime mesenchymal stem cells to peptide ghrelin and enhance chondrogenesis and osteochondral defect repair in vivo.

Mesenchymal stem cells (MSCs) are important cell sources in cartilage tissue development and homeostasis, and multiple strategies have been developed to improve MSCs chondrogenic differentiation with an aim of promoting cartilage regeneration. Here we report the effects of combining nanosecond pulsed electric fields (nsPEFs) followed by treatment with ghrelin (a hormone that stimulates release of growth hormone) to regulate chondrogenesis of MSCs. nsPEFs and ghrelin were observed to separately enhance the chondrogenesis of MSCs, and the effects were significantly enhanced when the bioelectric stimulation and hormone were combined, which in turn improved osteochondral tissue repair of these cells within Sprague Dawley rats. We further found that nsPEFs can prime MSCs to be more receptive to subsequent stimuli of differentiation by upregulated Oct4/Nanog and activated JNK signaling pathway. Ghrelin initiated chondrogenic differentiation by activation of ERK1/2 signaling pathway, and RNA-seq results indicated 243 genes were regulated, and JAK-STAT signaling pathway was involved. Interestingly, the sequential order of applying these two stimuli is critical, with nsPEFs pretreatment followed by ghrelin enhanced chondrogenesis of MSCs in vitro and subsequent cartilage regeneration in vivo, but not vice versa. This synergistic prochondrogenic effects provide us new insights and strategies for future cell-based therapies.

GDF15: emerging biology and therapeutic applications for obesity and cardiometabolic disease.

Growth differentiation factor 15 (GDF15) is a member of the TGFβ superfamily whose expression is increased in response to cellular stress and disease as well as by metformin. Elevations in GDF15 reduce food intake and body mass in animal models through binding to glial cell-derived neurotrophic factor family receptor alpha-like (GFRAL) and the recruitment of the receptor tyrosine kinase RET in the hindbrain. This effect is largely independent of other appetite-regulating hormones (for example, leptin, ghrelin or glucagon-like peptide 1). Consistent with an important role for the GDF15-GFRAL signalling axis, some human genetic studies support an interrelationship with human obesity. Furthermore, findings in both mice and humans have shown that metformin and exercise increase circulating levels of GDF15. GDF15 might also exert anti-inflammatory effects through mechanisms that are not fully understood. These unique and distinct mechanisms for suppressing food intake and inflammation makes GDF15 an appealing candidate to treat many metabolic diseases, including obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease, cardiovascular disease and cancer cachexia. Here, we review the mechanisms regulating GDF15 production and secretion, GDF15 signalling in different cell types, and how GDF15-targeted pharmaceutical approaches might be effective in the treatment of metabolic diseases.

Changes in ghrelin, substance P and vasoactive intestinal peptide levels in the gastroduodenal mucosa of patients with morbid obesity

AimsThe aim of the study was to assess changes in levels of substance P (SP), vasoactive intestinal peptide (VIP) and ghrelin in the gastroduodenal mucosa of obese individuals, which has not been studied before. MethodsForty-six patients with a body mass index (BMI) of >40 kg/m2 and 20 patients with a BMI of 18–25 kg/m2 were included in the study. VIP and SP levels in the fundus, antrum and duodenal mucosa were measured in freshly frozen tissues using enzyme-linked immunosorbent assay (ELISA). Fasting levels of ghrelin in blood were also measured with ELISA. Tissue levels of ghrelin were assessed by immunohistochemical staining, and immunoreactivity scores were used for ghrelin evaluation in tissues. ResultsAntrum SP levels were higher in the obese group than in the control group. A significant number of obese patients had low VIP levels in the fundus and antrum. Intense ghrelin staining was observed in a limited number of cells in the mucosal area of the gastric fundus that was similar in the control and patient groups. In the antrum and duodenum, ghrelin staining was low in all the samples examined. ConclusionHere, we found that SP levels are increased, while VIP levels are decreased in the antrum of morbidly obese individuals. Previous studies show that SP increases gastroduodenal motility, that VIP slows it down, and that the gastric emptying rate is higher in obese individuals, preventing negative feedback mechanisms upon food intake. Therefore, increases in SP and decreases in VIP levels in the antrum may contribute to obesity by accelerating gastric emptying.

Effects of Adding Novel Fibre Composition to White Rice in a Meal on Glycemic, Insulinemic and Appetite Responses - A Randomized Controlled Trial

Abstract Objectives Using modern food technologies, a novel fibre composition was designed to reduce the glycemic response of white rice while maintaining its organoleptic properties. An increased intake of dietary fibre improves glycemic control and satiety. The incorporation of fibre into staple foods may be a viable dietary strategy against type 2 diabetes mellitus (T2DM) and obesity. This study investigated the postprandial glucose, insulin and appetite changes to a novel grain shape fibre composition, fibre grains, in a mixed meal. Methods A randomized, controlled, crossover feeding trial was conducted with 22 healthy adults. Participants were randomized to consume control and fiber grains in a meal. Primary outcomes measured were postprandial glucose and insulin levels. Appetite changes were assessed using a visual analogue scale (VAS) and gut hormones, ghrelin and glucagon-like peptide 1(GLP-1). Results The addition of fibre grains brought about a non-significant reduction in the 2 h postprandial glycemic and insulinemic responses. The rated satiety scores were not significantly different for desire to eat, hunger and fullness. However, prospective food intake was suppressed to a smaller extent following the consumption of fibre grain (mean area under the curve (AUC) ± SEM: −2888.9 ± 498.1 mm.min) compared to the control (−4615.2 ± 730.9 mm.min, p = 0.024). The postprandial ghrelin was found to be significantly larger for fibre grain meal (AUC: 9345.7 ± 4114.5 pg/ml.min) compared to the control (AUC: −7637.7 ± 5359.0 pg/ml.min, p = 0.031). The level of GLP-1 was also significantly larger after fibre grain meal (AUC: 1108.5 ± 114.9 pM/min) compared to the control (AUC: 877.4 ± 110.2 pM/min, p = 0.044). Conclusions The application of fibre grains at the current level did not significantly reduce the postprandial glycemic and insulinemic responses in a mixed meal. However, a significant increase in postprandial GLP-1 may have implications in blood glucose management and appetite control and warrants further studies. Funding Sources This study is supported by a joint project grant received from the National University of Singapore and National University Health System, Singapore, through the Health Innovation Programme. It is also supported by Alchemy Foodtech Pte. Ltd. Funding agencies have no role in data collection and interpretation.

Gastrointestinal Motility and Gut Hormone Secretion in response to Shenhuang Plaster in a Postoperative Ileus Rat Model.

Postoperative ileus (POI), a gastrointestinal function disorder, is a complication that arises from surgery. Shenhuang plaster (SHP) application to the Shenque acupoint (CV8) to promote the recovery of gastrointestinal function has achieved definite curative effects in clinical settings; however, the underlying pharmacological mechanism remains unknown. In this study, we evaluated the effects of SHP using a Sprague Dawley rat POI model. Then, gastrointestinal transit in different rat groups was evaluated by the movement of fluorescein-labelled dextran. Ghrelin, obestatin, motilin (MTL), and vasoactive intestinal peptide (VIP) plasma concentrations were measured via a radioimmunoassay. The expression of the ghrelin and obestatin receptors (GHS-R1α and GPR39) in the intestinal muscularis of rats in different groups was comparatively identified via western blotting. The results indicated that SHP application improved gastrointestinal motility in POI model rats. SHP application significantly increased ghrelin concentration and the expression of its receptor and inhibited obestatin concentration and the expression of its receptor in blood. Further, ghrelin concentration and the capability of gastrointestinal transit were positively correlated. Simultaneously, SHP application also promoted the secretion of other gastrointestinal motility hormones, such as MTL and VIP. Hence, these results provide evidence that SHP can promote the recovery of gastrointestinal transmission in POI rat models through regulation of ghrelin and other intestinal hormones.

Ghrelin and PYY in low-weight females with avoidant/restrictive food intake disorder compared to anorexia nervosa and healthy controls

BackgroundAvoidant/restrictive food intake disorder (ARFID) is characterized by restrictive eating and failure to meet nutritional needs but is distinct from anorexia nervosa (AN) because restriction is not motivated by weight/shape concerns. We examined levels of orexigenic ghrelin and anorexigenic peptide YY (PYY) in young females with ARFID, AN and healthy controls (HC). Methods: 94 females (22 low-weight ARFID, 40 typical/atypical AN, and 32 HC ages 10–22 years) underwent fasting blood draws for total ghrelin and total PYY. A subset also provided blood 30, 60 and 120 min after a standardized meal.Results:Females with ARFID ate less than those with AN or HC (ps<0.012); were younger (14.4 ± 3.2 years) than those with AN (18.9 ± 3.1 years) and HC (17.4 ± 3.1 years) (ps<0.003) and at a lower Tanner stage (3.1 ± 1.5) than AN (4.5 ± 1.1;) and HC (4.4 ± 1.1; ps<0.005), but did not differ in BMI percentiles or BMI Z-scores from AN (ps>0.44). Fasting and postprandial ghrelin were lower in ARFID versus AN (ps≤.015), but not HC (ps≥0.62). Fasting and postprandial PYY did not differ between ARFID versus AN or HC (ps≥0.13); ARFID did not demonstrate the sustained high PYY levels post-meal observed in those with AN and HC. Secondary analyses controlling age or Tanner stage and calories consumed showed similar results. Exploratory analyses suggest that the timing of the PYY peak in ARFID is earlier than HC, showing a peak PYY level 30 min post-meal (p = .037).Conclusions:ARFID and AN appear to have distinct patterns of secretion of gut-derived appetite-regulating hormones that may aid in differential diagnosis and provide new treatment targets.

Unusual orthologs shed new light on the binding mechanism of ghrelin to its receptor GHSR1a

The gastric peptide ghrelin has important functions in energy metabolism and cellular homeostasis by activating growth hormone secretagogue receptor type 1a (GHSR1a). The N-terminal residues of ghrelin orthologs from all vertebrates are quite conserved; however, in orthologs from Cavia porcellus and Phyllostomus discolor, Ser2 and Leu5 are replaced by a smaller Ala and a positively charged Arg, respectively. In the present study, we first demonstrated that the hydrophobic Leu5 is essential for the function of human ghrelin, because Ala replacement caused an approximately 100-fold decrease in activity. However, replacement of Leu5 by an Arg residue caused much less disruption; further replacement of Ser2 by Ala almost restored full activity, although the [S2A] mutation itself showed slight detriments, implying that the positively charged Arg5 in the [S2A,L5R] mutant might form alternative interactions with certain receptor residues to compensate for the loss of the essential Leu5. To identify the responsible receptor residues, we screened GHSR1a mutants in which all conserved negatively charged residues in the extracellular regions and all aromatic residues in the ligand-binding pocket were mutated separately. According to the decrease in selectivity of the mutant receptors towards [S2A,L5R]ghrelin, we deduced that the positively charged Arg5 of the ghrelin mutant primarily interacts with the essential aromatic Phe286 at the extracellular end of the sixth transmembrane domain of GHSR1a by forming cation−π and π−π interactions. The present study provided new insights into the binding mechanism of ghrelin with its receptor, and thus would facilitate the design of novel ligands for GHSR1a.

Relationship between Orexigenic Peptide Ghrelin Signal, Gender Difference and Disease.

Growth hormone secretagogue receptor 1a (GHS-R1a), which is one of the G protein-coupled receptors (GPCRs), is involved in various physiological actions such as energy consumption, growth hormone secretion promoting action, and cardiovascular protective action. The ligand was searched for as an orphan receptor for a while, but the ligand was found to be acylated ghrelin (ghrelin) discovered by Kangawa and Kojima et al. in 1999. Recently, it has also been reported that dysregulation of GHS-R1a mediates reduced feeding in various diseases. On the other hand, since the physiological effects of ghrelin have been studied exclusively in male mice, few studies have been conducted on gender differences in ghrelin reactivity. In this review, we describe (1) the characteristics of GHS-R1a, (2) the role of ghrelin in hypophagia due to stress or anticancer drugs, and (3) the gender differences in the physiological effects of GHS-R1a and the influence of stress on it.

Ghrelin Expression in Mast Cells of Infant Lung with Respiratory Distress Syndrome

Abstract This article sheds light on some features of ghrelin (GHR)- and tryptase (Try)-positive mast cells (MCs) distribution in human lung of preterm newborns with respiratory distress syndrome (RDS). GHR possessed anti-inflammatory activity and reliable therapeutic properties in some lung diseases. So far, GHR expression has been defined predominantly in neuroendocrine cells of bronchial mucosa in fetal and infant lungs. Lung tissue from 8 dead newborns with RDS were investigated immunohistochemically with anti-GHR and anti-Try antibodies. The number of GHR+ and Try+ MCs was determined in three locations –bronchi, bronchiole and in alveolar septa. MCs were more numerous around main bronchi with diminishing numbers around bronchiole and in alveolar septa. The number of MCs in the latter was increased in newborns with pneumonia. The number of GHR+ MCs in alveolar septa was lower in newborns with RDS as compared to newborns with RDS combined with pneumonia (2.83 ± 1.13 vs 4.81 ± 2.6, p &lt; 0.001). The amount of Try+ MCs along bronchial wall was significantly more than GHR+ MCs in RDS newborns (6.97 ± 4.53 vs 3.85 ± 4.30, p = 0.001). It could be supposed that pulmonary MCs increased in newborn lungs in inflammatory process. MCs in human lung contained GHR peptide that had immunomodulatory function and participated in hormone regulation of inflammation.

Can a Higher Protein/Low Glycemic Index vs. a Conventional Diet Attenuate Changes in Appetite and Gut Hormones Following Weight Loss? A 3-Year PREVIEW Sub-study

Background: Previous research showed that weight-reducing diets increase appetite sensations and/or circulating ghrelin concentrations for up to 36 months, with transient or enduring perturbations in circulating concentrations of the satiety hormone peptide YY.Objective: This study assessed whether a diet that is higher in protein and low in glycemic index (GI) may attenuate these changes.Methods: 136 adults with pre-diabetes and a body mass index of ≥25 kg/m2 underwent a 2-month weight-reducing total meal replacement diet. Participants who lost ≥8% body weight were randomized to one of two 34-month weight-maintenance diets: a higher-protein and moderate-carbohydrate (CHO) diet with low GI, or a moderate-protein and higher-CHO diet with moderate GI. Both arms involved recommendations to increase physical activity. Fasting plasma concentrations of total ghrelin and total peptide YY, and appetite sensations, were measured at 0 months (pre-weight loss), at 2 months (immediately post-weight loss), and at 6, 12, 24, and 36 months.Results: There was a decrease in plasma peptide YY concentrations and an increase in ghrelin after the 2-month weight-reducing diet, and these values approached pre-weight-loss values by 6 and 24 months, respectively (P = 0.32 and P = 0.08, respectively, vs. 0 months). However, there were no differences between the two weight-maintenance diets. Subjective appetite sensations were not affected by the weight-reducing diet nor the weight-maintenance diets. While participants regained an average of ~50% of the weight they had lost by 36 months, the changes in ghrelin and peptide YY during the weight-reducing phase did not correlate with weight regain.Conclusion: A higher-protein, low-GI diet for weight maintenance does not attenuate changes in ghrelin or peptide YY compared with a moderate-protein, moderate-GI diet.Clinical Trial Registry: ClinicalTrials.gov registry ID NCT01777893 (PREVIEW) and ID NCT02030249 (Sub-study).

Ghrelin peptide improves glial conditioned medium effects on neuronal differentiation of human adipose mesenchymal stem cells

The influences of ghrelin on neural differentiation of adipose-derived mesenchymal stem cells (ASCs) were investigated in this study. The expression of typical neuronal markers, such as protein gene product 9.5 (PGP9.5) and Microtubule Associated Protein 2 (MAP2), as well as glial Fibrillary Acid Protein (GFAP) as a glial marker was evaluated in ASCs in different conditions. In particular, 2 µM ghrelin was added to control ASCs and to ASCs undergoing neural differentiation. For this purpose, ASCs were cultured in Conditioned Media obtained from Olfactory Ensheathing cells (OEC-CM) or from Schwann cells (SC-CM). Data on marker expression were gathered after 1 and 7 days of culture by fluorescence immunocytochemistry and flow cytometry. Results show that only weak effects were induced by the addition of only ghrelin. Instead, dynamic ghrelin-induced modifications were detected on the increased marker expression elicited by glial conditioned media. In fact, the combination of ghrelin and conditioned media consistently induced a further increase of PGP9.5 and MAP2 expression, especially after 7 days of treatment. The combination of ghrelin with SC-CM produced the most evident effects. Weak or no modifications were found on conditioned medium-induced GFAP increases. Observations on the ghrelin receptor indicate that its expression in control ASCs, virtually unchanged by the addition of only ghrelin, was considerably increased by CM treatment. These increases were enhanced by combining ghrelin and CM treatment, especially at 7 days. Overall, it can be assumed that ghrelin favors a neuronal rather than a glial ASC differentiation.

A ghrelin receptor antagonist reduces the ability of ghrelin, alcohol or amphetamine to induce a dopamine release in the ventral tegmental area and in nucleus accumbens shell in rats

The orexigenic peptide ghrelin increases the release of dopamine in the nucleus accumbens (NAc) shell via central ghrelin receptors, especially those located in the ventral tegmental area (VTA). The activity of the VTA dopamine neurons projecting to NAc shell, involves somatodendritic dopamine release within the VTA. However, the effects of ghrelin on the concomitant dopamine release in the VTA and NAc shell is unknown. It is further unknown whether addictive drugs, such as alcohol and amphetamine, enhance the dopamine levels in both these areas via ghrelin receptor dependent mechanisms. Thus, the effects of a ghrelin receptor antagonist, JMV2959, on the ability of i) central ghrelin ii) systemic alcohol or iii) systemic amphetamine to increase the dopamine release in the VTA and in the NAc shell in rats by using in vivo microdialysis was explored. We showed that systemic administration of JMV2959 blocks the ability of central ghrelin to increases dopamine release in the VTA and the NAc shell, and reduces the alcohol- and amphetamine-induced dopamine release in both these areas. Locomotor activity studies was then conducted in an attempt to correlate the ghrelin-induced dopamine release in the VTA to a behavioural outcome. These revealed that local infusion of a dopamine D1 receptor antagonist into the VTA blocks the ability of central ghrelin to cause a locomotor stimulation in mice. Collectively, this study adds to the growing body of evidence indicating that ghrelin signalling modulates the ability of ghrelin, and addictive drugs, to activate the mesoaccumbal dopamine pathway.

Evaluation of serum ghrelin, nesfatin-1, irisin, and vasoactive intestinal peptide levels in temporal lobe epilepsy patients with and without drug resistance: a cross-sectional study.

Epilepsy is a common disorder that affects the nervous systems of 1% of worldwide population. In epilepsy, one-third of patients are unresponsive to current drug therapies and develop drug-resistant epilepsy. Alterations in ghrelin, nesfatin-1, and irisin levels with epilepsy were reported in previous studies. Vasoactive intestinal peptide is among the most common neuropeptides in the hippocampus, which is the focus of the seizures in temporal lobe epilepsy. However, there is also lack of evidence of whether these four neuropeptide levels are altered with drug resistant temporal lobe epilepsy or not. The aim herein was the evaluation of the serum levels of nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide in drug-resistant temporal lobe epilepsy patients and temporal lobe epilepsy (TLE) without drug resistance, and to compare them to healthy controls. This cross-sectional study group included 58 temporal lobe epilepsy patients (24 with drug resistant temporal lobe epilepsy and 34 with temporal lobe epilepsy who were not drug-resistant) and 28 healthy subjects. Nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide serum levels were determined using enzyme-linked immunosorbent assay. The serum ghrelin levels of patients with drug resistant temporal lobe epilepsy were seen to have significantly decreased when compared to those of the control group (p<0.05). Serum nesfatin-1, vasoactive intestinal peptide, and irisin levels were seen to have decreased in the drug resistant temporal lobe epilepsy group when compared to those of the control and temporal lobe epilepsy groups; however, the difference was non-significant (p>0.05). The results herein suggested that ghrelin might contribute to the pathophysiology of drug resistant temporal lobe epilepsy. However, further studies are needed to confirm this hypothesis.