Changes In Plasma Ghrelin Levels Research Articles

An ingestible, battery-free, tissue-adhering robotic interface for non-invasive and chronic electrostimulation of the gut

Ingestible electronics have the capacity to transform our ability to effectively diagnose and potentially treat a broad set of conditions. Current applications could be significantly enhanced by addressing poor electrode-tissue contact, lack of navigation, short dwell time, and limited battery life. Here we report the development of an ingestible, battery-free, and tissue-adhering robotic interface (IngRI) for non-invasive and chronic electrostimulation of the gut, which addresses challenges associated with contact, navigation, retention, and powering (C-N-R-P) faced by existing ingestibles. We show that near-field inductive coupling operating near 13.56 MHz was sufficient to power and modulate the IngRI to deliver therapeutically relevant electrostimulation, which can be further enhanced by a bio-inspired, hydrogel-enabled adhesive interface. In swine models, we demonstrated the electrical interaction of IngRI with the gastric mucosa by recording conductive signaling from the subcutaneous space. We further observed changes in plasma ghrelin levels, the “hunger hormone,” while IngRI was activated in vivo, demonstrating its clinical potential in regulating appetite and treating other endocrine conditions. The results of this study suggest that concepts inspired by soft and wireless skin-interfacing electronic devices can be applied to ingestible electronics with potential clinical applications for evaluating and treating gastrointestinal conditions.

Changes in plasma ghrelin levels following surgical and non-surgical weight-loss in female rats predict alcohol use

The weight-loss surgery Roux-en Y gastric bypass (RYGB) is a relatively effective, long-term treatment option for patients with morbid obesity. However, accumulating clinical evidence suggests that patients receiving RYGB may be at increased risk of developing alcohol use disorder. This observation has been repeatedly supported by preclinical studies showing rodents increase intake of ethanol (EtOH) after RYGB, and has been further confirmed by human studies. A promising alternative to RYGB is sleeve gastrectomy (SG), which has resulted in decreased EtOH consumption in some rodent studies. The exact mechanism underlying the differential alcohol outcomes after RYGB versus SG has yet to be elucidated. However, the gut hormone ghrelin has emerged as a potential candidate from previous preclinical studies specific to RYGB surgeries and due to its action to stimulate food and alcohol intake and cravings. To directly assess changes in plasma ghrelin levels following weigh loss surgeries in the context of alcohol intake, 24 female rats were separated into three surgical groups receiving RYGB, SG, or Sham surgery followed by caloric restriction to produce adiposity matched controls (Sham-AM). Blood was drawn for fasted and fed plasma ghrelin (acyl and des-acyl) assays at multiple time points: while on a normal diet (ND), after 5-week exposure to a high fat diet (HFD), following surgery, and after a series of two-bottle alcohol choice test with increasing concentrations (2%, 4%, 6%, 8%) of EtOH. Consistent with previous observations, RYGB rats drank more EtOH than SG rats across all concentrations. As expected, fasted ghrelin levels were blunted after HFD feeding, compared to normal diet baseline. After RYGB, fasted ghrelin levels returned to higher levels while remained blunted after SG and Sham-AM. Fed acyl ghrelin levels were significantly increased to above “normal” levels after RYGB, but remain low after SG and Sham-AM. Given that post-RYGB acyl ghrelin levels are raised to a fasted state regardless of actual prandial status, we conclude that RYGB may results in a hormonal state reminiscence of a fasted state with the inability of feeding to inhibit ghrelin production, an effect which could potentially contribute to increased EtOH intake following the surgery. In contrast, following SG, ghrelin levels in rats remain consistent with the fed state regardless of prandial status, potentially explaining lower alcohol intake and lower risk of developing AUD.

Time-Restricted Feeding in Mice Prevents the Disruption of the Peripheral Circadian Clocks and Its Metabolic Impact during Chronic Jetlag.

We used time-restricted feeding (TRF) to investigate whether microbial metabolites and the hunger hormone ghrelin can become the dominant entraining factor during chronic jetlag to prevent disruption of the master and peripheral clocks, in order to promote health. Therefore, hypothalamic clock gene and Agrp/Npy mRNA expression were measured in mice that were either chronically jetlagged and fed ad libitum, jetlagged and fed a TRF diet, or not jetlagged and fed a TRF diet. Fecal short-chain fatty acid (SCFA) concentrations, plasma ghrelin and corticosterone levels, and colonic clock gene mRNA expression were measured. Preventing the disruption of the food intake pattern during chronic jetlag using TRF restored the rhythmicity in hypothalamic clock gene mRNA expression of Reverbα but not of Arntl. TRF countered the changes in plasma ghrelin levels and in hypothalamic Npy mRNA expression induced by chronic jetlag, thereby reestablishing the food intake pattern. Increase in body mass induced by chronic jetlag was prevented. Alterations in diurnal fluctuations in fecal SCFAs during chronic jetlag were prevented thereby re-entraining the rhythmic expression of peripheral clock genes. In conclusion, TRF during chronodisruption re-entrains the rhythms in clock gene expression and signals from the gut that regulate food intake to normalize body homeostasis.

253-OR: Plasma Ghrelin Changes and Successful Weight Loss in Patients with Obesity: The POUNDS Lost Trial

The orexigenic gut hormone, ghrelin, has been implicated in the regulation of appetite, energy homeostasis, and adiposity. We investigated associations of plasma ghrelin changes after consuming weight loss diets with improvements in general adiposity, body fat accumulation, and energy metabolism among overweight and obese adults. We also tested whether short-term ghrelin changes in response to weight-loss diets were predictive of long-term successful weight loss. This study included 217 overweight and obese adults who participated in a weight-loss diet intervention study, the POUNDS Lost trial. Plasma ghrelin levels were measured at baseline and 6 months after the intervention. We examined associations of the 6-month changes in plasma ghrelin levels from the baseline with changes in weight, waist circumference (WC), body fat composition assessed by dual-energy X-ray absorptiometry (DEXA), fat distribution assessed by CT scans, and resting energy expenditure (REE). At baseline, higher ghrelin levels were significantly associated with lower adiposity (weight, WC, and body fat composition) and REE (p <0.05 for all). We found that plasma ghrelin levels tended to be increased at 6 months after the intervention among the total participants (with a median 6-month change of 77 pg/ml). Greater increases in plasma ghrelin were associated with larger decreases in weight (p <0.001), WC (p =0.002), trunk fat % (p <0.001), whole-body fat % (p <0.001), total adipose tissue (p=0.007), as well as REE (p=0.01). Further, greater 6-month increases in ghrelin levels were significantly associated with the achievement of successful weight loss (-5% or more weight reduction) at 1 year (P for linear trend=0.0059). Our study suggests that weight-loss diet-induced increases in ghrelin are associated with improvements in adiposity and body fat composition. Plasma ghrelin changes in response to weight-loss diets may be predictive of long-term weight loss success among patients with overweight and obesity. Disclosure Y. Heianza: None. Q. Xue: None. G. Bray: None. F. Sacks: None. L. Qi: None. J. Tong: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (DK091718, DK100383, DK115679)

Plasma ghrelin levels after percutaneous electrical nerve stimulation of dermatome T6 for the treatment of obesity

IntroductionObese patients often find it difficult to adhere to long-term low-calorie diets. One of the reasons for dietary failure is the permanent feeling of hunger. Ghrelin is an orexigenic hormone, secreted by enterochromaffin cells in the gastric fundus.The aim of this study was to analyze changes in plasma ghrelin levels after PENS of dermatome T6 associated to a low-calorie diet, as well as changes in appetite and weight loss, as compared to a control group on a low-calorie alone. Material and methodsA prospective, non-randomized study was conducted including 20 patients who underwent PENS of dermatome T6 associated to a low-calorie diet before undergoing bariatric surgery to lose weight (Group 1), and 20 patients who were only prescribed a low-calorie diet before surgery (Group 2). In Group 1, plasma ghrelin levels were measured at 5 timepoints: before the first PENS session (Sample 1a); after the first PENS session (Sample 1b); before the last PENS session (Sample 2a); after the last PENS session (Sample 2b); and one month after treatment completion (Sample 3). In Group 2, only two samples were collected: before the start of the diet (Sample 1) and after 12 weeks of diet (Sample 2). ResultsAfter 12 weeks of treatment, BMI decreases of 8.42±2.6% and 1.32±0.98% were seen in Group 1 and Group 2 respectively (p=0.007). A significant decrease was seen in ghrelin levels between samples 1a and 2a, and between samples 1a and 3. In Group 2, a non-significant increase was seen in ghrelin levels. ConclusionPENS of dermatome T6 was associated to decreased plasma ghrelin levels. This therapy, associated to a low-calorie diet, achieves a BMI reduction greater than 8% after 12 weeks of treatment.

Fasting ghrelin levels after gastric bypass and vertical sleeve gastrectomy: An analytical cohort study

Background and objectiveNeuronal populations involved in the regulation of food intake, particularly the orexigenic (appetite-stimulating) hormone ghrelin, are found in the hypothalamus. Changes in plasma ghrelin levels have been observed following different bariatric surgery procedures, but the results from different studies are contradictory. Much remains unknown regarding the role of ghrelin in the weight loss process following bariatric surgery.Our objective was to describe the behavior of fasting ghrelin levels, comparing the changes occurring between 2 different surgical techniques (gastric bypass versus vertical sleeve gastrectomy) and their correlation with weight loss. Patients and methodA prospective, observational, analytic cohort study of 54 patients (27 for each surgical technique) with a 12-month follow-up period. We analyzed demographic data, anthropometric data, comorbidities, weight loss and evolution of fasting ghrelin. ResultsThe behavior of acylated ghrelin was similar with the 2 surgical techniques, with no significant differences between gastric bypass and vertical sleeve gastrectomy. With both procedures, there was an increase in acylated ghrelin on day 5 and a subsequent decrease, and levels then gradually increased to reach values at 12 months that were higher than those reported preoperatively. This increase in ghrelin levels did not affect weight loss, since one year post-surgery, 30% weight loss was achieved with both types of surgery. ConclusionsWe observed an increase in fasting acylated ghrelin levels at one year of follow-up with both surgical techniques, with 30% weight loss.

Evaluación de la grelina plasmática tras aplicación de neuroestimulación percutánea del dermatoma T6 en el tratamiento de la obesidad

IntroductionObese patients often find it difficult to adhere to long-term low-calorie diets. One of the reasons for dietary failure is the permanent feeling of hunger. Ghrelin is an orexigenic hormone, secreted by enterochromaffin cells in the gastric fundus.The aim of this study was to analyze changes in plasma ghrelin levels after PENS of dermatome T6 associated to a low-calorie diet, as well as changes in appetite and weight loss, as compared to a control group on a low-calorie alone. Material and methodsA prospective, non-randomized study was conducted including 20 patients who underwent PENS of dermatome T6 associated to a low-calorie diet before undergoing bariatric surgery to lose weight (Group 1), and 20 patients who were only prescribed a low-calorie diet before surgery (Group 2). In Group 1, plasma ghrelin levels were measured at 5 timepoints: before the first PENS session (Sample 1a); after the first PENS session (Sample 1b); before the last PENS session (Sample 2a); after the last PENS session (Sample 2b); and one month after treatment completion (Sample 3). In Group 2, only two samples were collected: before the start of the diet (Sample 1) and after 12 weeks of diet (Sample 2). ResultsAfter 12 weeks of treatment, BMI decreases of 8.42%±2.6% and 1.32%±0.98% were seen in Group 1 and Group 2 respectively (p=0.007). A significant decrease was seen in ghrelin levels between samples 1a and 2a, and between samples 1a and 3. In Group 2, a non-significant increase was seen in ghrelin levels. ConclusionPENS of dermatome T6 was associated to decreased plasma ghrelin levels. This therapy, associated to a low-calorie diet, achieves a BMI reduction greater than 8% after 12 weeks of treatment.

Comportamiento de ghrelina en ayunas después de bypass gástrico y gastrectomía vertical: estudio de cohortes analítico

Background and objectiveNeuronal populations involved in the regulation of food intake, particularly the orexigenic (appetite-stimulating) hormone ghrelin, are found in the hypothalamus. Changes in plasma ghrelin levels have been observed following different bariatric surgery procedures, but the results from different studies are contradictory. Much remains unknown regarding the role of ghrelin in the weight loss process following bariatric surgery.Our objective was to describe the behaviour of fasting ghrelin levels, comparing the changes occurring between 2 different surgical techniques (gastric bypass versus vertical sleeve gastrectomy) and their correlation with weight loss. Patients and methodA prospective, observational, analytic cohort study of 54 patients (27 for each surgical technique) with a 12-month follow-up period. We analysed demographic data, anthropometric data, comorbidities, weight loss and evolution of fasting ghrelin. ResultsThe behaviour of acylated ghrelin was similar with the 2 surgical techniques, with no significant differences between gastric bypass and vertical sleeve gastrectomy. With both procedures, there was an increase in acylated ghrelin on day 5 and a subsequent decrease, and levels then gradually increased to reach values at 12 months that were higher than those reported preoperatively. This increase in ghrelin levels did not affect weight loss, since one year post-surgery, 30% weight loss was achieved with both types of surgery. ConclusionsWe observed an increase in fasting acylated ghrelin levels at one year of follow-up with both surgical techniques, with 30% weight loss.

Pancreatogenic diabetes mellitus – Prevalence and risk factors

The gut peptide hormone ghrelin induces appetite and exhibits an anti-inflammatory effect. Serial perioperative changes in ghrelin have been examined in several surgical procedures, but few in pancreatectomy. The present study analyzed perioperative changes in plasma ghrelin levels after pancreaduodenectomy (PD).The study included 24 patients undergoing PD between May 2015 and January 2016 at Osaka University Hospital. Plasma ghrelin and interleukin-6 (IL-6) levels, as well as white blood cells (WBCs) and C-reactive protein (CRP), were measured preoperatively and on postoperative day (POD) 1, 3, 7, and 14 by enzyme-linked immunosorbent assay. The relationship between the individual ghrelin ratio relative to preoperative value (IGR) and the development of grade IIIa-V Clavien-Dindo (CD) complications was examined.Twelve patients (50%) developed grade IIIa CD complications (n = 6 [25%] pancreatic fistula, n = 7 [29%] intraabdominal abscess, n = 3 [13%] post-pancreatectomy hemorrhage, n = 5 [21%] wound infection, and n = 1 [4%] lymphorrhea). The IGR on POD 1 was significantly lower (p = 0.014) in patients who developed the complications compared to those who did not, but no significant differences were found in terms of WBC, CRP, or IL-6 on POD 1. When the IGR cut-off was set to 82% by receiver operative curve analysis, the sensitivity was 83%, specificity 75% and area under the curve 0.80. The lower IGR group (≤82%) had more postoperative complications and longer hospital stay.The IGR on POD 1 after PD is a useful marker for predicting postoperative complications.

Role of Hunger Hormone "Ghrelin" in Long-Term Weight Loss Following Laparoscopic Sleeve Gastrectomy.

Introduction:Laparoscopic sleeve gastrectomy (LSG) has become a popular weight loss technique in morbidly obese patients. The aim of our study was to evaluate the changes in plasma ghrelin levels in relation to weight loss following LSG and to study the efficacy of LSG in terms of long-term glycemic control and resolution of diabetes.Methodology:The study was conducted on 70 morbidly obese patients (body mass index [BMI] >40 kg/m2) or severely obese patients (BMI >35 kg/m2) with comorbidities who underwent LSG in Dayanand Medical College and Hospital, Ludhiana, India. Ghrelin levels were measured preoperatively and postoperatively at 1 week, 3 months, and 6 months along with measurements of various weight loss parameters and glycosylated hemoglobin.Results:A significant decrease in plasma ghrelin levels was observed in relation to the mean weight and percentage excess weight loss at 3 months postoperatively. However, at 6 months, fall in ghrelin reached a plateau phase while weight loss was still sustained and significant. There was a significant fall in glycosylated hemoglobin levels with patients achieving good control/resolution of diabetes Type II.Conclusion:LSG is an effective weight loss surgery and brings about excellent weight loss in morbidly obese individuals in addition to achievement of good glycemic control in diabetic individuals. Serum levels of ghrelin fall significantly after sleeve gastrectomy. However, long term implications of ghrelin induced weight loss cannot be elucidated.

Gastric Mucosal Changes and Ghrelin Expression and Their Relation to Weight Reduction After Sleeve Gastrectomy

Background: Weight loss after laparoscopic sleeve gastrectomy (LSG) is usually attributed to the volume restrictive effect of the procedure in addition to specific hormonal changes. Objective: The present study aimed to investigate the changes in plasma ghrelin levels, the number of ghrelin producing cells and histopathological changes in the remaining pouch after LSG. Methods: The present study included 27 patients with morbid obesity. The plasma ghrelin levels were measured before and six months after LSG and the change in their levels was assessed in relation to body mass index (BMI) after LSG. Immunohistochemical staining of cellular ghrelin was used to evaluate the number and distribution of ghrelin producing cells in the resected specimen and the mucosal changes in the remaining gastric pouch after LSG were assessed at 6 months postoperatively. Results: The mean age of patients was 33.9± 21.9 years. At six months after LSG, BMI decreased from 52.6± 12.8 to 40.8± 7.2 Kg/m² (p= 0.0001). The plasma ghrelin level decreased significantly from 564.1± 15 to 434.7± 22.6 at six months after LSG. There was strong positive correlation between BMI after LSG and plasma ghrelin level (R= 0.906, p= <0.0001). A significant improvement in the inflammatory parameters was noticed by histopathologic examination. The mean ghrelin positive cell per specimen decreased significantly from 25.37± 3.5 to 13.7 ± 2.12. Conclusion: There was good positive correlation between weight loss and lowering of plasma ghrelin level, also complete removal of the fundus was associated with more weight loss.

Plasma ghrelin suppression as an early predictor for postoperative complications after pancreatoduodenectomy

Background/ObjectivesThe gut peptide hormone ghrelin induces appetite and exhibits an anti-inflammatory effect. Serial perioperative changes in ghrelin have been examined in several surgical procedures, but few in pancreatectomy. The present study analyzed perioperative changes in plasma ghrelin levels after pancreaduodenectomy (PD). MethodsThe study included 24 patients undergoing PD between May 2015 and January 2016 at Osaka University Hospital. Plasma ghrelin and interleukin-6 (IL-6) levels, as well as white blood cells (WBCs) and C-reactive protein (CRP), were measured preoperatively and on postoperative day (POD) 1, 3, 7, and 14 by enzyme-linked immunosorbent assay. The relationship between the individual ghrelin ratio relative to preoperative value (IGR) and the development of grade IIIa-V Clavien-Dindo (CD) complications was examined. ResultsTwelve patients (50%) developed grade IIIa CD complications (n = 6 [25%] pancreatic fistula, n = 7 [29%] intraabdominal abscess, n = 3 [13%] post-pancreatectomy hemorrhage, n = 5 [21%] wound infection, and n = 1 [4%] lymphorrhea). The IGR on POD 1 was significantly lower (p = 0.014) in patients who developed the complications compared to those who did not, but no significant differences were found in terms of WBC, CRP, or IL-6 on POD 1. When the IGR cut-off was set to 82% by receiver operative curve analysis, the sensitivity was 83%, specificity 75% and area under the curve 0.80. The lower IGR group (≤82%) had more postoperative complications and longer hospital stay. ConclusionsThe IGR on POD 1 after PD is a useful marker for predicting postoperative complications.

Changes in plasma ghrelin levels accompanying a decrease in muscle volume can affect the prognosis of amyotrophic lateral sclerosis patients

Background: Alteration of nutritional status is a prognostic factor for patients with amyotrophic lateral sclerosis (ALS). Nutritional intervention may therefore positively impact their survival. However, these patients often suffer from anorexia, which may hinder nutritional intervention.

The effect of hydro-alcoholic extract of Achillea millefolium on appetite hormone in rats.

Achillea millefolium (A. millefolium) is known as an orexigenic herb in Iranian traditional medicine. In this study, the possible orexigenic effect of hydro-alcoholic extract of A. millefolium was investigated by measuring plasmaghrelin level. Thirty male Wistar rats were divided into five groups. Control group received water. Treatment groups received 50, 100 or 150 mg/kg of A. millefolium extract for 7 days via gavage. Before the intervention, daily amount of the food eaten by each rat was measured for 10 days. During the investigation, the amount of energy intake of each rat was also estimated 1, 2, 4, 6 and 24 hr after each intake, for 7 days. Later, the orexigenic dose of extract and distilled water was fed to two separate groups of 6 male Wistar rats. Plasma ghrelin level was measured 0.5, 1, 2 and 4 hrafter extract intake. The change in energy intake after treatment by 50and 100mg/kg of the extract was significantly higher than other groups (p<0.001).Administration of Achillea 100mg/kg significantly (p<0.05) decreased ghrelin level one hrafter intervention but there was no significant (p>0.05) difference among control and treated group. This study indicated that A. millefolium had positive dose-related effects on appetite in rats. It seems that the orexigenicactivity of extract was not related to changes in plasma ghrelin levels.

Overexpression of intraislet ghrelin enhances β-cell proliferation after streptozotocin-induced β-cell injury in mice

Previously, we reported that exogenous administration of ghrelin ameliorates glucose metabolism in a neonate streptozotocin (STZ)-induced diabetic rat model through enhancement of β-cell proliferation. However, it was not clear whether the observed β-cell proliferation was a direct or indirect effect (e.g., via orexigenic or growth hormone-stimulated pathways) of ghrelin activity. Here, we aimed to investigate whether ghrelin directly impacts β-cell proliferation after STZ-induced injury in mice. Seven-week-old male rat insulin II promoter-ghrelin internal ribosomal sequence ghrelin O-acyltransferase transgenic (RIP-GG Tg) mice, which have elevated pancreatic ghrelin levels, but only minor changes in plasma ghrelin levels when fed a medium-chain triglyceride-rich diet, were treated with STZ. Then, serum insulin, pancreatic insulin mRNA expression, and islet histology were evaluated. We found that the serum insulin levels, but not blood glucose levels, of RIP-GG Tg mice were significantly ameliorated 14 days post-STZ treatment. Pancreatic insulin mRNA expression was significantly elevated in RIP-GG Tg mice, and β-cell numbers in islets were increased. Furthermore, the number of phospho-histone H3⁺ or Ki67⁺ proliferating β-cells was significantly elevated in RIP-GG Tg mice, whereas the apoptotic indexes within the islets, as determined by TUNEL assay, were not changed. These results indicate that ghrelin can directly stimulate β-cell proliferation in vivo after β-cell injury even without its orexigenic or GH-stimulating activities, although it did not have enough impact to normalize the glucose tolerance in adult mice.

Reduction in total plasma ghrelin levels following catecholamine depletion: Relation to bulimic and depressive symptoms

There is increasing preclinical and clinical evidence of the important role played by the gastric peptide hormone ghrelin in the pathogenesis of symptoms of depression and eating disorders. To investigate the role of ghrelin and its considered counterpart, peptide tyrosine tyrosine (PYY), in the development of bulimic and depressive symptoms induced by catecholamine depletion, we administered the tyrosine hydroxylase inhibitor alpha-methyl-paratyrosine (AMPT) in a randomized, double-blind, placebo-controlled crossover, single-site experimental trial to 29 healthy controls and 20 subjects with fully recovered bulimia nervosa (rBN). We found a decrease between preprandial and postprandial plasma ghrelin levels (p<0.0001) and a postprandial rise in plasma PYY levels (p<0.0001) in both conditions in the entire study population. Plasma ghrelin levels decreased in the entire study population after treatment with AMPT compared to placebo (p<0.006). AMPT-induced changes in plasma ghrelin levels were negatively correlated with AMPT-induced depressive symptoms (p<0.004). Plasma ghrelin and plasma PYY levels were also negatively correlated (p<0.05). We did not observe a difference in ghrelin or PYY response to catecholamine depletion between rBN subjects and healthy controls, and there was no correlation between plasma ghrelin and PYY levels and bulimic symptoms induced by catecholamine depletion. These findings suggest a relationship between catecholamines and ghrelin with depressive symptoms.

Time dependent response in ghrelin levels in mesenteric ischemia in rat

The objective of this study was to determine the value of time-dependent ischemia-modified ghrelin in mesenteric ischemia. The authors investigated whether or not there is changes in plasma ghrelin levels in the acute period in a rat model of mesenteric ischemia were time-related. 42 mature male rats were divided into seven groups: one control and six ischemia groups. In the ischemia groups, following laparotomy the superior mesenteric artery (SMA) was ligated using a 2/0 silk suture, and blood samples were taken at 30, 60, 90, 120, 150 and 180 min. Plasma ghrelin levels in all the ischemia groups were significantly higher compared to the control group. In addition, the highest level of ghrelin was observed at 180 min. In our current study we have shown a direct increase in ghrelin in cases of acute mesenteric ischemia (AMI). This is a result of ghrelin’s protective effect against ischema/reperfusion (I/R) damage on the intestines, as in most of the other organs. With these characteristics, ghrelin can be easily applied in AMI and appears to be a prognosis parameter that can be used in clinics and needs no technological equipment or experience. Key words: Ischemia, superior mesenteric arteria, ghrelin, rat. INTRODUCTION Acute mesenteric ischemia (AMI) is one of many abdominal emergencies. It refers to a sudden onset of intestinal hypoperfusion, which can be due to an occlusive or a nonocclusive obstruction of arterial or venous blood flow (Stamatakos et al., 2008). AMI is caused by mesenteric occlusive vascular disease and is more common in adult patients who have additional cardiovascular problems, with a mortality rate of 30 to 90%. The causes of AMI in the pediatric age group include mesenteric vascular occlusion due to invasive aortic monitoring devices, neonatal aortic thrombosis,

Central Injection of the Stable Somatostatin Analog ODT8-SST Induces a Somatostatin2 Receptor-Mediated Orexigenic Effect: Role of Neuropeptide Y and Opioid Signaling Pathways in Rats

Somatostatin and octreotide injected into the brain have been reported to modulate food intake. However, little is known regarding the underlying mechanisms. The stable oligosomatostatin analog, des-AA(1,2,4,5,12,13)-[DTrp(8)]-somatostatin (ODT8-SST), like somatostatin, binds to all five somatostatin receptors (sst(1-5)). We characterized the effects of ODT8-SST injected intracerebroventricularly (i.c.v.) on food consumption and related mechanisms of action in freely fed rats. ODT8-SST (0.3 and 1 microg per rat, i.c.v.) injected during the light or dark phase induced an early onset (within 1 h) and long-lasting (4 h) increase in food intake in nonfasted rats. By contrast, i.p. injection (0.3-3 mg/kg) or i.c.v. injection of selective sst(1) or sst(4) agonists (1 microg per rat) had no effect. The 2 h food intake response during the light phase was blocked by i.c.v. injection of a sst(2) antagonist, the neuropeptide Y (NPY) Y(1) receptor antagonist, BIBP-3226, and ip injection of the mu-opioid receptor antagonist, naloxone, and not associated with changes in plasma ghrelin levels. ODT8-SST (1 microg per rat, i.c.v.) stimulated gastric emptying of a solid meal which was also blocked by naloxone. The increased food intake was accompanied by a sustained increase in respiratory quotient, energy expenditure, and drinking as well as mu-opioid receptor-independent grooming behavior and hyperthermia, while ambulatory movements were not altered after ODT8-SST (1 microg per rat, i.c.v.). These data show that ODT8-SST acts primarily through brain sst(2) receptors to induce a long-lasting orexigenic effect that involves the activation of Y(1) and opiate-receptors, accompanied by enhanced gastric transit and energy expenditure suggesting a modulation of NPYergic and opioidergic orexigenic systems by brain sst(2) receptors.

The effect of estrogens on plasma ghrelin concentrations in women

Data regarding the possible effects of estrogen on ghrelin secretion in humans are limited and contradictory. To investigate the effect of estradiol (E2) on ghrelin levels in normal pre- and post-menopausal women. A total of 21 women divided into 3 groups, i.e.13 normally cycling women (no.=7, group 1 and no.=6, group 2) and 8 post-menopausal women (group 3). Women of group 1 received increasing doses of E2 through skin patches from cycle days 3 to 5. Women of group 2, underwent total abdominal hysterectomy plus bilateral salpingo-oophorectomy (TAH+BSO) on cycle day 3. Women of group 3 received po increasing doses of E2 valerate for 15 days. Acylated ghrelin and E2 were measured in all blood samples. In group 1, plasma ghrelin levels did not show any significant changes for the week following cycle day 3. In group 2, ghrelin levels were similar before and after TAH+BSO and remained stable during the first 7 post-operative days. In group 3, no significant changes in plasma ghrelin levels were seen during the 15 days of E2 administration. The present study demonstrates for the first time that ghrelin values were not affected either by exogenous short-term estrogen administration to pre- and post-menopausal women or following ovariectomy in pre-menopausal women. It is suggested that ovarian hormones are not involved in the regulation of ghrelin secretion in women.

Persistent Correlation of Ghrelin Plasma Levels with Body Mass Index Both in Stable Weight Conditions and during Gastric-bypass-induced Weight Loss

Studies done on serial changes in plasma ghrelin levels after gastric bypass (GBP) have yielded contrasting results since decreased, unchanged, or increased levels have been reported in the literature. This study investigates whether or not GBP has an inhibitory effect on fasting ghrelin levels independently of weight loss. Fasting ghrelin levels were measured in 115 stable body weight females, classified as normal body weight (NW; body mass index (BMI)<25 kg/m2), overweight (OW; BMI 25-30 kg/m2), and obese subjects, divided in three subgroups with increasing BMI (BMI 30-40 kg/m2; BMI 40-50 kg/m2; BMI>50 kg/m2). Each obese subgroup showed significantly lower ghrelin levels as compared to both NW (p<0.0001) and OW subjects (p<0.05 or 0.005); however, no significant differences were observed within the three obese subgroups. Forty-nine obese patients underwent a GBP. Plasma ghrelin, measured at 3, 6, and 12 months after GBP, significantly increased from the sixth month on (p<0.0001). When patients were classified, at each postoperative time point, according to their actual BMI, ghrelin was significantly (p=0.0002) related to postoperative BMI and not significantly different from ghrelin measured in stable body weight conditions. Fasting ghrelin displays an inversely significant correlation with BMI in both stable body weight conditions and after GBP. No evidence was found that GBP had an effect on fasting ghrelin levels, independent of weight loss.