Increased Ghrelin Levels Research Articles

Patterned feeding induces neuroendocrine, behavioral and genetic changes that promote palatable food intake.

Selection of a healthy diet is the cornerstone for treating obesity and metabolic disease. Unfortunately, the majority of diets fail leading to weight regain and in some cases, pathological feeding behavior. We hypothesize that alternating bouts of caloric overconsumption and caloric restriction, behavioral manifestations of dieting induce neuroendocrine, behavioral and genetic changes that promote future bouts of palatable food intake. To test this hypothesis, we subjected male Long-Evans rats to a high-fat diet (HFD) feeding paradigm that induced a pattern of caloric overconsumption and caloric restriction. Under these conditions we measured operant responding for sucrose, pre-meal ghrelin secretion, the effects of peripheral ghrelin blockade on patterned feeding, HFD intake in an aversive environment and mRNA expression of the ghrelin receptor, orexin, orexin-1 and 2 receptors, and FTO in the medial prefrontal cortex, lateral hypothalamus and ventral tegmental area. Rats subjected to this feeding regimen displayed increased ghrelin levels prior to HFD exposure and blockade of this response attenuated patterned feeding behavior. In addition, patterned feeding promoted enhanced motivation for sucrose, diminished extinction of this response and increased HFD intake in an aversive environment. The neuroendocrine and behavioral changes correlated with increased hypothalamic expression of the ghrelin receptor and FTO. Collectively, these data indicate that patterns of feeding that include caloric overconsumption and caloric restriction induce neuroendocrine and neurobiological changes that signify an enhanced drive for palatable food.

Ghrelin and hormonal markers under exercise training in patients with heart failure with preserved ejection fraction: results from the Ex-DHF pilot study.

BackgroundOver 50% of patients with symptomatic heart failure (HF) experience HF with preserved ejection fraction (HFpEF). Exercise training (ET) is effective in improving cardiorespiratory fitness and dimensions of quality of life in patients with HFpEF. A systemic pro‐inflammatory state induced by comorbidities as the cause of myocardial structural and functional alterations has been proposed in HFpEF. ET modifies myocardial structure and has been related to inflammatory state. We investigated Ghrelin, related adipokines, markers of inflammation, and neuro‐hormonal activation in patients undergoing a structured ET vs. usual care are with HFpEF. Methods and resultsEx‐DHF‐P was a prospective, controlled, randomized multi‐centre trial on structured and supervised ET in patients with HFpEF. We performed a post hoc analysis in 62 patients from Ex‐DHF‐P. Ghrelin, adiponectin, leptin, IL‐1ß, IL‐6, IL‐10, tumour necrosis factor‐alpha, MR‐proANP, MR‐proADM, CT‐proET1, and CT‐proAVP were assessed to seize the impact of ET on these markers in patients with HFpEF. Thirty‐six (58%) patients were female, mean age was 64 years, and median ghrelin was 928 pg/mL (interquartile range 755–1156). When stratified for high versus low ghrelin, groups significantly differed at baseline in presence obesity, waist circumference, and adiponectin levels (P < 0.05, respectively). Overall, ghrelin levels rose significantly to 1013 pg/mL (interquartile range 813–1182) (P < 0.001). Analysis of covariance modelling for change in ghrelin identified ET (P = 0.013) and higher baseline adiponectin levels (P = 0.035) as influencing factors.ConclusionsExercise training tended to increase ghrelin levels in Ex‐DHF‐P. This increase was especially pronounced in patients with higher baseline adiponectin levels. Future trials are needed to investigate the effect of ET on endogenous ghrelin levels in regard to interactions with cardiac structure and clinically meaningful surrogate parameters.

Acute and short-term effects of caloric restriction on metabolic profile and brain activation in obese, postmenopausal women.

Early anthropometric and metabolic changes during a caloric-restricted diet in obese postmenopausal women and correlations between these factors with activity in brain areas involved in processing of visual food related stimuli were investigated. An 8-week prospective intervention study of 18 healthy postmenopausal women, with a body mass index of 30-35 kg m-2. The first 2 weeks subjects were on an isocaloric diet and 4 weeks on a 1000 kcal restricted diet followed by 2 weeks on an isocaloric diet. Anthropometric and laboratory analyses were performed weekly during the isocaloric diet and three times a week during the caloric-restricted diet. Functional magnetic resonance imaging scans were obtained before and after the caloric restriction in four separate sessions (fasting or sated). Generalized Estimating Equations analysis was used for data analysis. A mean weight loss of 4.2±0.5 kg (4.8%) and a 4.2±0.4 cm decline in waist circumference were achieved. In the first week of caloric restriction, triglyceride, leptin, resistin and adiponectin levels as well as systolic blood pressure decreased and insulin-like growth factor-binding protein 1 levels increased. During and after weight loss, a significant increase in ghrelin levels was observed. Before weight loss, increased activation of the right amygdala was seen in response to food stimuli, and free fatty acids and glucose correlated with activity in various areas involved in food reward processing. After weight loss, fasting ghrelin and sated leptin levels correlated with activity in these areas. Already in the first week of caloric restriction in obese postmenopausal women, various favourable metabolic changes occur before clinically relevant weight loss is achieved. Activity in the amygdala region and correlations of metabolic factors with activity in brain areas involved in food reward processing differ substantially before and after weight loss.

Weight Regain Following Sleeve Gastrectomy-a Systematic Review.

Sleeve gastrectomy (SG) is a commonly performed bariatric procedure. Weight regain following SG is a significant issue. Yet the defining, reporting and understanding of this phenomenon remains largely neglected. Systematic review was performed to locate articles reporting the definition, rate and/or cause of weight regain in patients at least 2years post-SG. A range of definitions employed to describe weight regain were identified in the literature. Rates of regain ranged from 5.7% at 2years to 75.6% at 6years. Proposed causes of weight regain included initial sleeve size, sleeve dilation, increased ghrelin levels, inadequate follow-up support and maladaptive lifestyle behaviours. Bariatric literature would benefit from standardising definitions used to report weight regain and its rate in clinical series. Larger prospective studies are required to further understand mechanisms of weight regain following SG.

An Integrative Review on Role and Mechanisms of Ghrelin in Stress, Anxiety and Depression.

Ghrelin is orexigenic hormone primarily synthesized by endocrine X/A-like cells of gastric oxyntic mucosa to stimulate appetite and food intake along with regulation of growth hormone and insulin secretion; glucose and lipid metabolism; gastrointestinal motility; blood pressure, heart rate and neurogenesis. Furthermore, peripherally (after crossing the blood brain barrier) as well as centrally synthesized ghrelin (in the hypothalamus) regulates diverse functions of central nervous system including stress-associated behavioral functions. Exposure to stress alters the ghrelin levels and alteration in ghrelin levels significantly affects neuro-endocrinological parameters; metabolism-related physiology, behavior and mood. Studies have shown both anxiolytic and anxiogenic role of ghrelin suggesting its dual role in modulating anxiety-related behavior. However, it is proposed that increase in ghrelin levels during stress condition is an endogenous stress coping behavior and increased ghrelin levels may be required to prevent excessive anxiety. In preclinical and clinical studies, an elevation in ghrelin levels during depression has been correlated with their antidepressant activities. Ghrelin-induced modulation of stress and associated conditions has been linked to alteration in hypothalamic-pituitary-adrenal (HPA) axis; autonomic nervous system (mainly sympathetic nervous system and serotonergic neurotransmission. A reciprocal relationship has been reported between corticotropin-releasing hormone (CRH) and ghrelin as ghrelin increases the release of CRH, ACTH and corticosteroids; while CRH decreases the expression of ghrelin. Similarly, ghrelin increases the serotonin turnover and in turn, serotonin controls ghrelin signaling to modulate anxiety-related behavior. The present review discusses the dual role of ghrelin in stress and related behavioral disorders along with possible mechanisms.

Increased Ghrelin Levels and Unchanged Adipocytokine Levels in Major Depressive Disorder.

One of the hypotheses of the pathophysiology of major depressive disorder (MDD) proposes that there is a relationship between adipocytokine and ghrelin levels and depression. Patients with major depression with a BMI ≤25 kg/m2 between the ages of 11 and 18 years (n = 30) were compared with a healthy control group (n = 30). Both groups were evaluated across a pretreatment period (MD-PT) and an improved period (MD-I). We measured serum leptin, adiponectin, resistin, and ghrelin levels and other parameters related to metabolic syndrome, such as glucose, insulin, insulin resistance (homeostasis model assessment [HOMA]), triglycerides (TG), and total cholesterol (TCHOL). Leptin, adiponectin, and resistin levels did not differ across groups; however, ghrelin levels were increased in the MD-I group compared with the control and MD-PT groups (p < 0.05). HOMA levels were also higher in the MD-PT group than in the control group (p < 0.05). After treatment, there was no difference in this measurement. The relationship between adipocytokines and major depression may be dependent on ghrelin levels as a result of antidepressant treatment and subsequent obesity.

Appetite Suppression and Antiobesity Effect of a Botanical Composition Composed of Morus alba, Yerba mate, and Magnolia officinalis.

Background. Obesity and its comorbidities continue to challenge the world at an alarming rate. Although the long term solution lies on lifestyle changes in the form of dieting and exercising, drug, medical food, or dietary supplement interventions are required for those who are already obese. Here we describe a standardized blend composed of extracts from three medicinal plants: Morus alba, Yerba mate, and Magnolia officinalis for appetite suppression and metabolic disorders management. Method. Extracts were standardized to yield a composition designated as UP601. Appetite suppression activity was tested in acute feed intake rat model. Efficacy was evaluated in C57BL/6J mouse models treated with oral doses of 1.3 g/kg/day for 7 weeks. Orlistat at 40 mg/kg/day was used as a positive control. Body compositions of mice were assessed using a dual energy X-ray absorptiometry (DEXA). ELISA was done for insulin, leptin, and ghrelin level quantitation. Nonalcoholic steatohepatitis (NASH) scoring was conducted. Results. Marked acute hypophagia with 81.8, 75.3, 43.9, and 30.9% reductions in food intake at 2, 4, 6, and 24 hours were observed for UP601. Decreases in body weight gain (21.5% compared to the HFD at weeks 7 and 8.2% compared to baseline) and calorie intake (40.5% for the first week) were observed. 75.9% and 46.8% reductions in insulin and leptin, respectively, 4.2-fold increase in ghrelin level, and reductions of 18.6% in cholesterol and 59% in low-density lipoprotein were documented. A percentage body fat of 18.9%, 47.8%, 46.1%, and 30.4% was found for mice treated with normal control, HFD, Orlistat, and UP601, respectively. 59.3% less mesenteric fat pad and improved NASH scores were observed for UP601. Conclusion. UP601, a standardized botanical composition from Morus alba, Yerba mate, and Magnolia officinalis could be used as a natural alternative for appetite suppression, maintaining healthy body weight and metabolism management.

Elevated ghrelin predicts food intake during experimental sleep restriction.

ObjectiveSleep curtailment has been linked to obesity, but underlying mechanisms remain to be elucidated. We assessed whether sleep restriction alters 24-hour profiles of appetite-regulating hormones ghrelin, leptin and pancreatic polypeptide during a standardized diet, and whether these hormonal alterations predict food intake during ad libitum feeding.MethodsNineteen healthy, lean men were studied under normal sleep and sleep restriction in a randomized crossover design. Blood samples were collected for 24-hours during standardized meals. Subsequently, participants had an ad libitum feeding opportunity (buffet meals and snacks) and caloric intake was measured.ResultsGhrelin levels were increased after sleep restriction as compared to normal sleep (p<0.01). Overall, sleep restriction did not alter leptin or pancreatic polypeptide profiles. Sleep restriction was associated with an increase in total calories from snacks by 328 ± 140 Kcal (p=0.03), primarily from carbohydrates (p=0.02). The increase in evening ghrelin during sleep restriction was correlated with higher consumption of calories from sweets (r=0.48, p=0.04).ConclusionsSleep restriction as compared to normal sleep significantly increases ghrelin levels. The increase in ghrelin is associated with more consumption of calories. Elevated ghrelin may be a mechanism by which sleep loss leads to increased food intake and the development of obesity.

Ghrelin and GHS-R in the rat gastric mucosa: Are they involved in regulation of growth during early weaning?

ObjectivesBased on previous evidence showing that early weaning disturbs the ontogenesis of rat gastric glands, which are the major site of ghrelin synthesis, we investigated the distribution of ghrelin and its receptor (GHS-R) in the rat gastric epithelium during postnatal development and evaluated the effects of early weaning on their levels. Additionally, we studied the contribution of ghrelin to gastric growth during the abrupt nutrient transition. MethodsWistar rats were submitted to early weaning at 15 d and suckling counterparts were taken as controls. ResultsBy running quantitative reverse transcription polymerase chain reaction, immunoblots, and immunohistochemistry, we detected a variation of ghrelin levels and an increase of expression and number of immunolabeled cells, 3 d after treatment (P < 0.05). Through confocal microscopy, we identified GHS-R in the neck region of the gland and did not observe changes in protein levels. Growth was evaluated after ghrelin antagonist ([d-Lys-3]-GHRP-6) administration, which reduced DNA synthesis index in early-weaned rats (P < 0.05) as determined by bromodeoxyuridine incorporation. ConclusionThe present study demonstrated that ghrelin and GHS-R are distributed in gastric mucosa during the postnatal development, indicating that they can signal and function in epithelial cells. We concluded that early weaning increased ghrelin levels in the stomach, and it takes part of cell proliferation control that is essential for stomach growth. Therefore, among the many effects previously described for early weaning, this abrupt nutrient transition also changed ghrelin levels, which might represent an additional element in the complex mechanism that coordinates stomach development.

Effects of high frequency stimulation of nucleus accumbens shell subregion on food intake in obesity rats and regulation of appetite-related hormones

Objective To explore the effects of chronic high frequency deep brain stimulation (DBS) of nucleus accumbens shell subregion on food intake and regulation of appetite-related hormones. Methods High-fat diet induced obesity rats were randomly divided into two groups, namely DBS group and sham-DBS group.Stimulating electrodes were implanted in the bilateral shell subregion of nucleus accumbens. The amount of food intake was measured before and during stimulation.Peripheral concentrations of ghrelin, NPY, and leptin were tested before and after DBS or sham-DBS. Results The amount of food intake began to significantly decrease once stimulation was on. After 7 days'continuous stimulation, peripheral concentrations of NPY and leptin decreased significantly (Leptin: pre-DBS: 32±10 vs.post-DBS: 20±10pg/ml, P<0.05; NPY: pre-DBS: 1 302±287 vs. post-DBS: 926±299 pg/ml, P<0.05), and ghrelin increased significantly (Pre-DBS: 1066±310 vs. Post-DBS: 1603±848 pg/ml, P<0.05). Conclusions NAc shell subregion is an effective DBS target to decrease food intake in obesity rats. NAc-shell DBS seems to temporarily inhibit the hypothalamic secretion of NPY. Increase of ghrelin levels maybe a second result of decreased food intake caused by NAc-shell stimulation. Key words: Deep brain stimulation; Nucleus accumbens; Obesity; Ghrelin; Leptin; Neuropeptide Y; Rats

The Levels of Ghrelin in Children with Cyanotic and Acyanotic Congenital Heart Disease

The cause of growth retardation in congenital heart disease is multifactorial. The relationship between congenital heart disease (CHD), malnutrition, and growth retardation is well documented. Ghrelin has effects on nutrient intake and growth. Ghrelin exerts potent GH-releasing activity and stimulates food intake. Circulating ghrelin levels are increased in anorexia and cachexia, reduced in obesity and restored by weight recovery. The relation between ghrelin and congenital heart disease is evident in adults but it is not studied well in pediatric age. The aim of the present study is to evaluate the serum ghrelin in congenital heart disease. We measured serum ghrelin, using ELISA technique in 60 patients with congenital heart disease (20 with acyanotic congenital heart disease with no heart failure (HF), 15 with cyanotic congenital heart disease with no HF) and 25 patients with congenital heart disease (cyanotic or acyanotic) with HF, in addition to 30 age and sex matched children as a control group. All children were subjected to measurement of height, weight, body mass index (BMI). In comparison to controls, serum ghrelin levels were significantly higher in patients with congenital heart disease (acyanotic patients and cyanotic with or without HF than in the control group (p=0.01). Also ghrelin level was significantly increased in children with cyanotic congenital heart disease than in those with acyanotic congenital heart disease. Patient with congenital heart disease with evidence of HF had significant higher levels of serum ghrelin than those with congenital heart disease without HF. Weight, height and BMI were significantly lower in cyanotic and acyanotic patients compared to the control group (p=0.001), also these measures were significantly reduced in patients with congenital heart disease with HF than in those without heart failure. There was a significant negative correlation between serum ghrelin and BMI in patients with heart failure, cyanotic patients and acyanotic patients; (r = -0.608, -0.831 and -0.458) and (p = 0.007, 0.02 and 0.017) respectively. In onclusion, serum ghrelin levels is elevated in children with acyanotic and cyanotic congenital heart disease with or without HF. Increased ghrelin levels represents malnutrition and growth retardation in these patients. This may suggest that ghrelin may have an important role as a compensatory mechanism in the regulation of the metabolic balance in these patients.

Relation between ghrelin level and treatment response in functional constipation

Ghrelin stimulates gastrointestinal motility. Although there are some experimental and clinical studies supporting the role of ghrelin for gastrointestinal motility disorders, limited research for constipation has been published. The purpose of this study was to evaluate the possible role of ghrelin in the pathophysiology of functional constipation in childhood. Forty-three newly diagnosed constipated children aged 1-6 years and 25 healthy age-matched controls were included. Serum ghrelin levels were analyzed initially in both groups. Treatment protocol consisted of dietary modification, lactulose, and administration of pediatric enema. Ghrelin levels of children with functional constipation were reanalyzed after two monthsof treatment. Initial serum ghrelin levels of constipated patients were found to be lower than those of healthy children (p<0.001). Ghrelin levels increased during therapy. The differences between initial and second month serum ghrelin levels of constipated patients were found to be statistically significant (p<0.05). Our data supports the potential role of ghrelin in children with functional constipation. Observation of an increase in serum ghrelin levels with nonspecific treatment supports the hypothesis that low serum ghrelin levels might be a result rather than the cause of constipation.

Short Duration of Sleep Is Associated with Hyperleptinemia in Taiwanese Adults

Higher plasma levels of leptin have been associated with increased cardiometabolic risk. The aim of this study was to investigate the association between short duration of sleep and hyperleptinemia in Taiwanese adults. We examined the association between duration of sleep and hyperleptinemia in 254 men and women recruited from the physical examination center at a regional hospital in southern Taiwan. Hyperleptinemia was defined as a plasma leptin level of 8.13 ng/mL and above. Short sleep duration was defined as < 6.5 h/day. Multiple logistic regression analysis was used to assess the association between short duration of sleep and hyperleptinemia. In females, short duration of sleep (< 6.5 h/day; OR = 2.15, 95% CI = 0.99-4.78), greater hip circumference (OR = 3.00, CI = 1.13-8.78), higher percent body fat (OR = 1.75, CI = 1.07-2.95), and higher white blood cell counts (OR = 1.67, CI = 1.26-2.28) were associated with an increased risk of hyperleptinemia. In males, greater body weight was significantly associated with an increased risk of hyperleptinemia (OR = 3.55, 95% CI = 1.46-10.23). There was also a trend of association (p = 0.096) between short duration of sleep and an increased risk of hyperleptinemia (OR = 4.98, 95% CI = 0.80-42.40). In this study of healthy Taiwanese adults, short duration of sleep was significantly associated with hyperleptinemia in women, and the association was independent of adiposity.

Long-term Changes in Leptin, Chemerin and Ghrelin Levels Following Different Bariatric Surgery Procedures: Roux-en-Y Gastric Bypass and Sleeve Gastrectomy

Different studies have evaluated changes in adipo/cytokine levels after bariatric surgery and have given conflicting results. The adipo/cytokines, leptin and chemerin, and the orexigenic hormone, ghrelin, have been shown to play a role in the regulation of metabolism and appetite. The aims of our study were to test the levels of these molecules after bariatric surgery and to compare the results between Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy. We analysed circulating levels of chemerin, ghrelin and leptin in 30 morbidly obese women (body mass index of >40 kg/m2). Subjects were studied at three time points: baseline (before the surgery started), and after 6 and 12 months. After surgery, chemerin (baseline, 95.03 ± 23.79; after 12 months, 76.80 ± 21.51; p = 0.034) and leptin levels (baseline, 248.17 ± 89.16; after 12 months, 63.85 ± 33.48; p < 0.001) were significantly lower than their baseline levels, whereas ghrelin was higher (baseline, 0.87 ± 0.38; after 12 months, 1.08 ± 0.31; p = 0.010). Fasting glucose, insulin and homeostasis model assessment of insulin resistance levels were markedly lower postoperatively. High-density lipoprotein levels moderately increased and triglyceride levels sharply decreased. There were no differences between the types of bariatric surgery in terms of weight reduction, general metabolic state or adipo/cytokine levels after surgery. Our study demonstrates a marked decrease in fasting leptin and chemerin levels, and an increase in ghrelin levels, after bariatric surgery-induced weight loss, independently of the type of surgery performed. Further studies are needed on the interrelation between the changes in the circulating levels of these molecules and the efficacy of the bariatric surgery procedures to induce the beneficial metabolic changes and to sustain body weight loss.

THU0407 Serum ghrelin and obestatin levels in behçet’s disease

BackgroundGhrelin is a potent endogenous orexigenic peptide controlling food intake and energy expenditure.It is produced by inflammatory cells in addition to gastric cells and mediates anti-inflammatory effects. Moreover, increased ghrelin...

Ghrelin and Its Relation with N-Terminal Brain Natriuretic Peptide, Endothelin-1 and Nitric Oxide in Patients with Idiopathic Pulmonary Hypertension

Objectives: To investigate ghrelin levels in patients with idiopathic pulmonary arterial hypertension (IPAH) and the association of ghrelin with N-terminal brain natriuretic peptide (N-BNP), endothelin-1 (ET-1) and nitric oxide (NO). Methods: Plasma ghrelin, N-BNP, ET-1 and NO were measured, and echocardiography was performed in 20 IPAH patients and in 20 control subjects matched for age, sex and body mass index. Results: Plasma ghrelin and NT-proBNP levels were significantly higher in IPAH patients compared with values in control subjects (p < 0.05). In IPAH patients, ghrelin levels correlated positively with N-BNP (r = 0.616, p = 0.004), NO (r = 0.464, p = 0.039), right ventricle diameter (RVD; r = 0.485, p = 0.030) and pulmonary arterial systolic pressure (PASP; r = 0.591, p = 0.006). N-BNP levels correlated positively with RVD (r = 0.551, p = 0.012) and ET-1 (r = 0.451, p = 0.046). Conclusions: Plasma ghrelin levels were elevated in IPAH. Increased ghrelin levels correlated positively with N-BNP, PASP, RVD and NO, and N-BNP levels correlated positively with RVD and ET-1. Pulmonary vascular pathology is a complex imbalance of opposing forces. Ghrelin may not only provide a novel prognostic biomarker for IPAH but also be a potential new therapeutic strategy.

Relationships between changes in leptin and insulin resistance levels in obese individuals following weight loss

Obesity can augment insulin resistance (IR), leading to increased risk of diabetes and heart disease. Leptin, ghrelin, and various fatty acids present in the cell membrane may modulate IR. In this study, we aimed to investigate the impact of weight loss on IR, serum leptin/ghrelin levels, and erythrocyte fatty acids, and studied the associations between changes in these variables. A total of 35 obese (body mass index ≥ 27) adults participated in a weight loss program for 3 months. IR was assessed using homeostasis model assessment for insulin resistance (HOMA-IR). The obese participants had a mean weight loss of 5.6 ± 3.8 kg followed by a 16.7% and 23.3% reduction in HOMA-IR and leptin (p < 0.001) levels, and an 11.3% increase in ghrelin levels (p = 0.005). The level of erythrocyte saturates decreased by 2.8%, while the level of n–3 polyunsaturates increased by 16.8% (all p < 0.05). The changes in leptin levels (−5.63 vs. −1.57 ng/mL) were significantly different (p = 0.004) in those with improved IR (changes in HOMA-IR < 0) than those without improvement (changes in HOMA-IR ≥ 0), though there were no differences in the changes of ghrelin (p = 0.120) and erythrocyte fatty acids (all p > 0.05) levels. After adjusting for age, gender, changes in ghrelin, and body fat, we found a significant correlation between decreases in leptin and less risk of no improvement in HOMA-IR levels [odds ratio (OR) = 0.69, p = 0.039]. In conclusion, a moderate weight reduction in obese participants over a short period significantly improved IR. This weight reduction concomitantly decreased serum leptin, increased ghrelin, and elevated some erythrocyte unsaturates. Only leptin correlated independently with IR improvement upon multivariable logistic regression analysis, which indicates that leptin may play a role in the modulation of IR following weight loss.

Intravenous injection of urocortin 1 induces a CRF2 mediated increase in circulating ghrelin and glucose levels through distinct mechanisms in rats

Urocortins (Ucns) injected peripherally decrease food intake and gastric emptying through peripheral CRF2 receptors in rodents. However, whether Ucns influence circulating levels of the orexigenic and prokinetic hormone, ghrelin has been little investigated. We examined plasma levels of ghrelin and blood glucose after intravenous (iv) injection of Ucn 1, the CRF receptor subtype involved and underlying mechanisms in ad libitum fed rats equipped with a chronic iv cannula. Ucn 1 (10μg/kg, iv) induced a rapid onset and long lasting increase in ghrelin levels reaching 68% and 219% at 0.5 and 3h post injection respectively and a 5-h hyperglycemic response. The selective CRF2 agonist, Ucn 2 (3μg/kg, iv) increased fasting acyl (3h: 49%) and des-acyl ghrelin levels (3h: 30%) compared to vehicle while the preferential CRF1 agonist, CRF (3μg/kg, iv) had no effect. <!-- no-mfc -->Ucn 1's<!-- /no-mfc --> stimulatory actions were blocked by the selective CRF2 antagonist, astressin2-B (100μg/kg, iv). Hexamethonium (10mg/kg, sc) prevented Ucn 1-induced rise in total ghrelin levels while not altering the hyperglycemic response. These data indicate that systemic injection of Ucns induces a CRF2-mediated increase in circulating ghrelin levels likely via indirect actions on gastric ghrelin cells that involves a nicotinic pathway independently from the hyperglycemic response.

Ghrelin Levels Increase After Pictures Showing Food

The neuropeptide ghrelin is a major signal for food intake in various species including humans. After exogenous ghrelin administration, food intake and body weight increase in rodents. In normal human subjects, ghrelin administration increases self-rated appetite and calorie intake and prompts the imagination of favorite meals. It is unclear so far whether ghrelin levels are affected by external cues such as sight of food. We investigated the influence of pictures showing food compared to neutral pictures on ghrelin levels in young normal male subjects (n = 8). The study consisted of two consecutive sessions with a one-week interval. During each session, blood for later analysis of plasma concentrations of ghrelin was collected between 08:15 and 13:00 every 15 min (between 10:30 and 11:30 every 10 min). Breakfast and lunch was provided at 08:30 and 12:00, respectively. Fifty pictures were presented from 10:30 to 10:45 showing neutral images during the first session and food contents during the second session. As expected, ghrelin levels increased before each meal independent of the picture contents. In addition, ghrelin levels during the 30-min interval following the presentation of pictures with food increased significantly compared to the 30-min interval before this presentation (area under the curve (AUC): 188 % vs. 158 %, P < 0.05). The difference in the increases between the two picture conditions was also significant (P < 0.05). Our findings suggest that sight of food elevates ghrelin levels in healthy volunteers.

Association of Ghrelin Receptor Promoter Polymorphisms with Weight Loss Following Roux-en-Y Gastric Bypass Surgery

Ghrelin plays a role in appetite and has been hypothesized to play a role in the mechanism of Roux-en-Y gastric bypass (RYGB) surgery. Single nucleotide polymorphisms (SNPs) in the promoter region of its receptor gene (growth hormone secretagogue receptor type 1a--GHSR) have also been associated with weight loss outcomes following long-term dietary intervention in adults with impaired glucose tolerance. Our objectives were to evaluate changes in serum ghrelin levels and determine the effect of GHSR promoter polymorphisms on post-RYGB surgery weight loss. Preoperative and 6-month postoperative serum ghrelin levels were measured in 37 patients with extreme obesity undergoing RYGB surgery. Total ghrelin was also measured in liver tissue collected intraoperatively. Association analysis between genotypes for SNPs rs9819506 and rs490683 in the promoter region of the GHSR gene and weight loss outcomes in the 30 months following surgery was performed in over 650 RYGB patients. Serum ghrelin levels increased after RYGB surgery. Weight loss trajectories were significantly different using an additive model for both ghrelin SNPs, with patients homozygous for the rs490683 CC genotype exhibiting the most weight loss. Weight loss trajectories were also different using a dominant model. The rs490683 risk allele demonstrated decreased promoter activity in vitro. The role of increased ghrelin levels in weight loss outcomes following RYGB surgery may be influenced by variation in the GHSR gene.