Higher Ghrelin Concentrations Research Articles

Ghrelin is related to lower brain reward activation during touch.

The gut hormone ghrelin drives food motivation and increases food intake, but it is also involved in the anticipation of and response to rewards other than food. This pre-registered study investigated how naturally varying ghrelin concentrations affect the processing of touch as a social reward in humans. Sixty-seven volunteers received slow caressing touch (so-called CT-targeted touch) as a social reward and control touch on their shins during 3T functional imaging on two test days. On one occasion, participants were fasted, and on another, they received a meal. On each occasion, plasma ghrelin was measured at three time points. All touch was rated as more pleasant after the meal, but there was no association between ghrelin concentrations and pleasantness. CT-targeted touch was rated as the most pleasant and activated somatosensory and reward networks (whole brain). A region-of-interest in the right medial orbitofrontal cortex (mOFC) showed lower activation during all touches, the higher the ghrelin concentrations were. During CT-targeted touch, a larger satiety response (ghrelin decrease after the meal) was associated with higher mOFC activation, and this mOFC activation was associated with higher experienced pleasantness. Overall, higher ghrelin concentrations appear to be related to a lower reward value for touch. Ghrelin may reduce the value of social stimuli, such as touch, to promote food search and intake in a state of low energy. This suggests that the role of ghrelin goes beyond assigning value to food reward.

Influence of electroacupuncture on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase signaling pathway in spontaneously hypertensive rats

ObjectiveTo investigate the influence of electroacupuncture (EA) on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway in spontaneously hypertensive rats (SHRs). MethodsEight Wistar-Kyoto rats were used as the healthy blood pressure (BP) control (normal group), and 32 SHRs were randomized into model group, EA group, EA plus ghrelin group (EA + G group), and EA plus PF04628935 group (a potent ghrelin receptor blocker; EA + P group) using a random number table. Rats in the normal group and model group did not receive treatment, but were immobilized for 20 min per day, 5 times a week, for 4 continuous weeks. SHRs in the EA group, EA + G group and EA + P group were immobilized and given EA treatment in 20 min sessions, 5 times per week, for 4 weeks. Additionally, 1 h before EA, SHRs in the EA + G group and EA + P group were intraperitoneally injected with ghrelin or PF04628935, respectively, for 4 weeks. The tail-cuff method was used to measure BP. After the 4-week intervention, the rats were sacrificed by cervical dislocation, and pathological morphology of the abdominal aorta was observed using hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ghrelin, nitric oxide (NO), endothelin-1 (ET-1) and thromboxane A2 (TXA2) in the serum. Isolated thoracic aortic ring experiment was performed to evaluate vasorelaxation. Western blot was used to measure the expression of PI3K, Akt, phosphorylated Akt (p-Akt) and eNOS proteins in the abdominal aorta. Further, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure the relative levels of mRNA expression for PI3K, Akt and eNOS in the abdominal aorta. ResultsEA significantly reduced the systolic BP (SBP) and diastolic BP (DBP) (P < 0.05). HE staining showed that EA improved the morphology of the vascular endothelium to some extent. Results of ELISA indicated that higher concentrations of ghrelin and NO, and lower concentrations of ET-1 and TXA2 were presented in the EA group (P < 0.05). The isolated thoracic aortic ring experiment demonstrated that the vasodilation capacity of the thoracic aorta increased in the EA group. Results of Western blot and qRT-PCR showed that EA increased the abundance of PI3K, p-Akt/Akt and eNOS proteins, as well as expression levels of PI3K, Akt and eNOS mRNAs (P < 0.05). In the EA + G group, SBP and DBP decreased (P < 0.05), ghrelin concentrations increased (P < 0.05), and the concentrations of ET-1 and TXA2 decreased (P < 0.05), relative to the EA group. In addition, the levels of PI3K and eNOS proteins, the p-Akt/Akt ratio, and the expression of PI3K, Akt and eNOS mRNAs increased significantly in the EA + G group (P < 0.05), while PF04628935 reversed these effects. ConclusionEA effectively reduced BP and protected the vascular endothelium, and these effects may be linked to promoting the release of ghrelin and activation of the PI3K/Akt/eNOS signaling pathway.

Overweight and obesity in type 1 diabetes is not associated with higher ghrelin concentrations

BackgroundSeveral studies have demonstrated suppressed levels of acylated (AG) and unacylated ghrelin (UAG) in patients with type 2 diabetes. However, the role of these hormones in type 1 diabetes has not been extensively studied. This study assessed the relationship between AG and UAG levels and body composition in patients with type 1 diabetes.MethodsWe selected eighteen patients with type 1 diabetes and divided them into two groups: non-obese (BMI < 25 kg/m2) and overweight (BMI ≥ 25 kg/m2). Demographics, parameters of body composition and serum parameters including AG and UAG, were assessed.ResultsThe patients with a BMI ≥ 25 kg/m2 were older and had a longer duration of diabetes. AG and UAG levels were not significantly different between non-obese and overweight groups (mean AG non-obese ± SD: 44.5 ± 29.4 pg/ml and mean UAG non-obese 42.4 ± 20.7 pg/ml vs mean AG overweight ± SD: 46.1 ± 29.6 pg/ml and mean UAG overweight 47.2 ± 18.2 pg/ml). AG/UAG ratios did not discriminate between these groups. There was a positive association of insuline dose/kg bodyweight with BMI (r2 = 0.45, p = 0.002).ConclusionsSurprisingly, unlike non-diabetics and in T2D, we did not observe a difference in plasma levels of AG and UAG between normal weight and overweight adult type 1 diabetics. However, we did observe a positive correlation between BMI and insuline dose/kg bodyweight, suggesting that exogenous insulin is more important than the ghrelin system in the development of obesity in type 1 diabetes.

Cord Blood IGF-I, Proinsulin, Leptin, HMW Adiponectin, and Ghrelin in Short or Skinny Small-for-Gestational-Age Infants.

Small-for-gestational-age (SGA) is an indicator of poor fetal growth "programming" an elevated risk of type 2 diabetes in adulthood. Little is known about early-life endocrine characteristics in SGA subtypes. Stunting (short) and wasting (skinny) are considered distinct SGA phenotypes in neonatal prognosis. This work aimed to assess whether SGA infants with stunting or wasting have similar alterations in neonatal endocrine metabolic health biomarkers. This was a nested case-control study based on the 3D (Design, Develop, and Discover) birth cohort in Canada. The study subjects were 146 SGA (birth weight < 10th percentile) and 155 optimal-for-gestational age (OGA, 25th-75th percentiles) infants. Stunting was defined as birth length less than the 10th percentile, and wasting as body mass index less than the 10th percentile for sex and gestational age, respectively. Main outcome measures included cord plasma concentrations of insulin-like growth factor I (IGF-I), proinsulin, leptin, high-molecular-weight (HMW) adiponectin, and ghrelin. Comparing to OGA infants adjusted for maternal and neonatal characteristics, SGA infants with either stunting only or wasting only had lower cord plasma IGF-I and leptin concentrations. HMW adiponectin concentrations were lower in SGA infants with wasting only (P = .004), but similar in SGA infants with stunting only (P = .816). Only SGA infants with both stunting and wasting had substantially lower proinsulin (P < .001) and higher ghrelin concentrations (P < .001) than OGA infants. This study is the first to demonstrate that SGA infants with wasting only are characterized by low HMW adiponectin concentrations, whereas those with stunting only are not. SGA with both stunting and wasting are characterized by low proinsulin and high ghrelin concentrations.

Strong Positive Correlation between TSH and Ghrelin in Euthyroid Non-Growth Hormone-Deficient Children with Short Stature.

The growth processes in children depend on the proper functioning of some hormones and growth factors. Recently, a positive correlation between ghrelin and TSH (thyroid stimulating hormone) in patients with hyper- and hypothyroidism was proved. Moreover, in hypothyroid rats with high ghrelin concentration, growth hormone (GH) and insulin-like growth factor I (IGF-I) secretion was suppressed. We analyzed these relationships in euthyroid prepubertal children with idiopathic short stature (ISS). The analysis comprised concentration of ghrelin, GH in stimulating tests and during the night, as well as IGF-I, TSH, free thyroxine (FT4) and free triiodothyronine (FT3) in 85 children with ISS (36 girls, 49 boys) aged 9.65 ± 3.02 years (mean ± SD). A strong positive correlation between ghrelin and TSH was confirmed (r = +0.44, p < 0.05). A higher ghrelin but lower nocturnal GH and lower IGF-I were observed in children with higher normal TSH concentration than those in children with lower normal TSH. Interestingly, alterations of TSH level were without any impact on FT4 and FT3 concentrations. Summing up, in ISS prepubertal euthyroid children, ghrelin and TSH secretion are closely related. On the other hand, the higher the TSH, the lower the nocturnal GH and IGF-I levels. The contribution of the above findings in deterioration of growth processes requires further studies.

Effects of Opuntia ficus-indica in the diet of primiparous sows on the metabolic profile during late gestation and lactation and feed intake during lactation.

The goal of this study was to evaluate the effects of dietary Opuntia ficus-indica L. (OFI) on the metabolic profile of primiparous sows during late gestation and lactation, and its impact on voluntary feed intake (VFI) during lactation. From day 85 of gestation to weaning, 32 sows were divided into four feeding schemes (n=8sows/scheme): Basal diet (BD) without OFI supplementation; Test scheme I, BD during gestation and BD+OFI during lactation; Test scheme II, BD+OFI during both gestation and lactation, and Test scheme III, BD+OFI during gestation and BD during lactation. Blood samples were obtained during gestation (day 85 and 100) and lactation (day 0, 3, 7, 14 and 21) to determine plasma glucose, insulin, triglycerides, leptin, osteocalcin, ghrelin and agouti-related protein (AgRP). VFI was higher (20% higher than that of controls) in sows that received dietary OFI during lactation (p<.05). The concentration of plasma glucose was lower in sows that consumed OFI than sows fed the conventional diet (p<.05). Plasma insulin concentrations were higher in sows that consumed OFI, than in sows that did not (p<.05). Triglyceride concentrations during gestation, farrowing and lactation were also lower in sows that consumed OFI (p<.05). OFI intake caused lower plasma concentrations of leptin during lactation (p<.05). Osteocalcin was higher in sows that consumed OFI versus controls (p<.05): 8.6% and 13.4% during gestation and lactation respectively. From day 3 of lactation, sows that consumed OFI had higher concentrations of ghrelin (p<.05). The concentration of plasma AgRP was higher (p<.05) in sows that consumed OFI versus controls: 3.1% and 14.2% in gestation and lactation respectively. We concluded that OFI intake by primiparous sows during late gestation and lactation favourably modulated the factors that caused insulin resistance and increased sow performance.

Metabolic state and value-based decision-making in acute and recovered female patients with anorexia nervosa

Patients with anorexia nervosa forgo eating despite emaciation and severe health consequences. Such dysfunctional decision-making might be explained by an excessive level of self-control, alterations in homeostatic and hedonic regulation, or an interplay between these processes. We aimed to understand value-based decision-making in anorexia nervosa and its association with the gut hormone ghrelin. Besides its homeostatic function, ghrelin has been implicated in the hedonic regulation of appetite and reward via the modulation of phasic dopamine signalling. In a cross-sectional design, we studied acutely underweight (n = 94) and recovered (n = 37) patients with anorexia nervosa of the restrictive subtype, as well as healthy control participants (n = 119). We assessed plasma concentrations of desacyl ghrelin and parameters of delay discounting, probability discounting for gains and losses, and loss aversion. Recovered patients displayed higher risk aversion for gains, but we observed no group differences for the remaining decision-making parameters. Desacyl ghrelin was higher in acutely underweight and recovered participants with anorexia nervosa relative to healthy controls. Moreover, we found a significant group × desacyl ghrelin interaction in delay discounting, indicating that in contrast to healthy controls, acutely underweight patients with anorexia nervosa who had high desacyl ghrelin concentrations preferably chose the delayed reward option. We probed decision-making using monetary rewards, but patients with anorexia nervosa may react differently to disorder-relevant stimuli. Furthermore, in contrast to acyl ghrelin, the functions of desacyl ghrelin are unclear. Therefore, the interpretation of the results is preliminary. The propensity for risk aversion as found in recovered patients with anorexia nervosa could help them successfully complete therapy, or it could reflect sequelae of the disorder. Conversely, ghrelin findings might be related to a mechanism contributing to disease maintenance; that is, in acutely underweight anorexia nervosa, a hungry state may facilitate the ability to forgo an immediate reward to achieve a (dysfunctional) long-term goal.

Association of hot flushes with ghrelin and adipokines in early versus late postmenopausal women.

Vasomotor flushing (hot flushes) is a common menopausal symptom experienced by most women going through the menopausal transition; flushing continues for a variable period in postmenopause. Primarily due to lack of ovarian estrogen, other biomarkers of hot flushes have not been clearly identified. We examined the relationship of hot flushes with ghrelin and adipokines. Baseline data from two clinical trials, the Women's Isoflavone Soy Health (WISH) trial and Early versus Late Intervention Trial of Estrogen (ELITE), were used in this post hoc cross-sectional study. Both WISH and ELITE had similar study designs, inclusion criteria, and data collection processes. Study participants were healthy postmenopausal women not taking estrogen-based hormone therapy, free of cardiovascular disease, or any other chronic diseases. Both trials used the same hot flush diary in which participants recorded the number of daily hot flushes by severity over a month on average. Serum concentrations of ghrelin, leptin, adiponectin, and resistin were assessed in stored fasting blood samples using highly specific radioimmunoassay. In this analysis, self-reported flushing experience was tested for an association with leptin, adiponectin, resistin, and ghrelin concentrations using logistic regression and mean comparisons. A total of 898 postmenopausal women from the ELITE and WISH trials contributed to this analysis. Mean (SD) age was 60.4 (7.0) years, body mass index (BMI) 27 (5.3) kg/m, 67% were white, and 47% were within 10 years of menopause. Reported flushing was significantly associated with younger age, lower education, lower BMI, being married, and more recent menopause. Adjusted for these factors other than BMI, women in the highest quartile of ghrelin had significantly greater likelihood of experiencing hot flushes (OR [95% CI] = 1.84 [1.21-2.85]) compared to women in the lowest quartile. The association was more pronounced among overweight or obese women (OR [95% CI] = 2.36 [1.28-4.35]) compared to those with normal BMI (1.24 [0.54, 2.86]; interaction P value = 0.46). The association between ghrelin and hot flushes was similar among early (within 10 y) and late (over 10 y) postmenopausal women. Blood levels of adiponectin and resistin were not associated with hot flushes. Higher concentrations of ghrelin were associated with greater likelihood of hot flushes in both early- and late-postmenopausal women. Leptin, adiponectin, and resistin levels were not associated with hot flushes in postmenopausal women.

Growth and feed intake regulation responses to anorexia, adaptation and fasting in Japanese seabss, Lateolabrax japonicas when fishmeal is totally replaced by plant protein

In captivity, Lateolabrax japonicas, a carnivorous fish, is given fishmeal-based diets and does not thrive when fed plant proteins. In the present study, when dietary fishmeal was totally replaced with plant protein, the fish showed anorexia in the first 2 weeks followed by the phenotypes of feeding adaptation and compensation after 4 weeks. The negative energy balance resulting from anorexia in fish given the plant-based diet induced up-regulation of ghrelin and down-regulation of leptin transcription in the stomach, along with high plasma ghrelin concentration, which indicated that the peripheral organs were effective at sensing the nutrients intake deficiency. However, activation of mTOR in the hypothalamus decreased the phosphorylation of downstream S6K1, accompanied by further up-regulation of anorectic gene POMC and down-regulation of orexigenic gene AgRP expression in anorectic stage, indicating that the central nervous system (CNS) failed to respond to peripheral hungry. As soon as the fish adapted to the plant protein diet, no matter pre-prandial or fasting for 3 weeks, the regulating responses in CNS were consistent with the peripheral energy state. Therefore, the voluntary anorexia induced by plant protein was under different regulation mechanism from feeding adaption and the passive feeding inhibition caused by fasting.

Relationship between IGF-I Concentration and Metabolic Profile in Children with Growth Hormone Deficiency: The Influence of Children's Nutritional State as well as the Ghrelin, Leptin, Adiponectin, and Resistin Serum Concentrations.

Background Some, however not all, children with growth hormone deficiency (GHD) reveal a tendency towards metabolic disorders. Insulin-like growth factor I (IGF-I) is the main mediator of GH anabolic effects. Objective The aim of the study was to compare ghrelin, adiponectin, leptin, resistin, lipid, glucose, and insulin concentrations in GHD children, depending on the IGF-I bioavailability. Methods The analysis comprised 26 children with GHD, aged 5.7–15.3 yrs. Fasting serum concentrations of IGF-I, IGFBP-3, ghrelin, leptin, adiponectin, resistin, lipids, glucose, and insulin were measured. The GHD children were divided into two subgroups: (1) with lower IGF-I/IGFBP-3 molar ratio and (2) with higher IGF-I/IGFBP-3 molar ratio. The control group consisted of 39 healthy children, aged 5.1–16.6 yrs, of normal height and body mass. Results GHD children with lower IGF-I/IGFBP-3 molar ratio were found to have a significantly lower body mass and insulin and triglyceride concentrations, as well as significantly higher ghrelin and adiponectin concentrations than GHD children with higher IGF-I/IGFBP-3. Conclusions A better metabolic profile characterised GHD children with low IGF-I bioavailability. This phenomenon may be the result of high adiponectin and ghrelin concentrations in those children and their influence on adipose tissue, glucose uptake, and orexigenic axis.

Lower Plasma Ghrelin Levels are Found in Women with Diabetes-Complicated Pregnancies.

Objective:To evaluate the associations of glycemic control and gestational age with ghrelin and proinsulin levels in cord blood and mothers’ peripheral blood during pregnancy.Methods:This is a cross-sectional comparative study of twenty-four pregnant women with gestational diabetes (GD), 18 with type 2 diabetes mellitus (T2DM), and 36 without diabetes, as well as their neonates. Levels of proinsulin, ghrelin, and glycated hemoglobin A1c (HbA1c) were measured from maternal blood during the last week before caesarian delivery and in neonatal umbilical cord blood samples.Results:Mothers with GD and T2DM had significantly lower ghrelin levels compared to the healthy mothers (p<0.001). Maternal proinsulin was lower in women with GD than in women without diabetes (p<0.001). Proinsulin was significantly elevated in the neonates of women with GD and in women with HbA1c ≥6.5% (p<0.001). However, maternal ghrelin levels were higher (p=0.031) and neonate proinsulin levels lower in the pre-term offspring of mothers with GD (p=0.033). There was a negative correlation between HbA1c levels and birth weight (r=–0.407, p<0.001).Conclusion:Ghrelin levels were lower in pregnant women with diabetes, although pre-term birth appeared to reverse this trend in GD. Proinsulin levels were also low in pregnant women with diabetes and even lower in pre-term vs. at-term births. Both ghrelin and proinsulin levels were lower in pregnant women with diabetes and HbA1c of <6.5%. Thus, ghrelin participates in the adaptation to the caloric imbalance of diabetic pregnancy and may play a similar role in pregnancy-related complications, since high ghrelin concentrations may be necessary for normal fetal development.

The impact of sugar sweetened beverage intake on hunger and satiety in minority adolescents

Limited research has examined the effects of habitual SSB consumption on hunger/fullness ratings and gut hormones. This study hypothesized that high versus low intakes of habitual SSBs would result in greater hunger, decreased fullness, and a blunted gut hormone response, however the high versus low fiber group would exhibit decreased hunger and increased fullness. This was a randomized crossover feeding trial with 47 African American and Hispanic adolescents. The experiment included three 24-hour recalls to assess habitual dietary intake. During the test meal phase, subjects were served breakfast and lunch. During the ad libitum meal phase, subjects were fed an ad libitum dinner. During the test meal phase, blood was drawn every 30 minutes for 3 hours. During the ad libitum meal phase, hunger and fullness visual analogue scales were completed. For this analysis, subjects were grouped into the following habitual SSB categories: low SSB (≤1 SSB serv/day), medium SSB (>1 - <2 serv/day), and high SSB (≥2 serv/day). Fiber categories were created based on quartiles of intake. Mixed modeling was used to explore how SSB and fiber categories predicted ghrelin/PYY values and hunger/fullness ratings across time within and between test meals. The following a priori covariates included: sex, ethnicity, age, and obesity status. The low SSB group had higher fullness ratings over the ad libitum meal compared to the high SSB group (β =-0.49, CI=(-0.89, -0.08), p=0.02) and higher ghrelin concentrations than the medium and high SSB group over the test meal phase (β =-1.86, CI=(-2.81, -0.92), p<0.01). Habitual SSB intake appears to play a key role in moderating fullness responses possibly via ghrelin.

Ghrelin and Leptin Have a Complex Relationship with Risk of Barrett's Esophagus.

Abdominal obesity is a risk factor for Barrett's esophagus independent of GERD symptoms, but little is understood about the biological mechanisms between obesity and the carcinogenic pathway of esophageal adenocarcinoma. To evaluate whether ghrelin and leptin may partially explain the association between obesity and Barrett's esophagus. We conducted a case-control study using patients with a new diagnosis of Barrett's esophagus (cases) and two control groups frequency matched to cases for age, gender, and geographic region: (1) patients with gastroesophageal reflux disease (GERD) and (2) a sample of the general population. We generated odds ratios using logistic regressions to evaluate quartiles of serum ghrelin or serum leptin, adjusting for known risk factors for Barrett's esophagus. We evaluated potential interaction variables using cross products and ran stratified analyses to generate stratum-specific odds ratios. A total of 886 participants were included in the analysis. Higher ghrelin concentrations were associated with an increased risk of Barrett's esophagus, when compared to the population controls, but not the GERD controls. Ghrelin concentrations were not associated with the frequency of GERD symptoms, but ghrelin's relationship with Barrett's esophagus varied significantly with the frequency of GERD symptoms. Leptin concentrations were positively associated with at least weekly GERD symptoms among the population controls and were inversely associated with Barrett's esophagus only among the GERD controls. Adjusting for waist circumference did not change the main associations. Higher levels of ghrelin were associated with an increased risk of Barrett's esophagus among the general population. In contrast, leptin was positively associated with frequent GERD symptoms, but inversely associated with the risk of Barrett's esophagus among the GERD controls.

Tu1206 Dyspeptic Symptoms in Inflammatory Bowel Diseases (IBD) Are Associated With Prolonged Gastric Emptying and High Serum Leptin Levels

Background: Symptoms compatible with GI functional disorders are higher in patients with IBD compared with controls. We demonstrated that delayed gastric emptying was associated with dyspeptic symptoms in inactive Crohn's disease. Serum ghrelin and leptin levels were elevated in IBD patients and it was described that these hormones couldmodify the gastrintestinal motility. High ghrelin or leptin serum concentrations are associated with symptoms in functional dyspepsia. The relationship between ghrelin and leptin with GI symptoms and gastric motility in IBD patients has not been studied. Aim: To investigate the relationship between dyspeptic symptoms, gastric emptying, serum levels of ghrelin and leptin in IBD. Methods: Twenty seven patients with IBD (14 with Crohn's disease and 13 with ulcerative colitis) underwent a gastric emptying test by breath test using 13C octanoic acid coupled to a solid meal and answered a validated questionnaire (PADYQ, The Porto Alegre Dyspeptic Symptoms Questionnaire) to assess dyspeptic symptoms; fasting blood samples were also collected to measure active ghrelin or leptin by a RIA. Then, IBD patients were allocated in two groups according to their total PADYQ score: non-dyspeptic (score=0), dyspeptic (score > 0). Control group was composed by 26 sex-matched healthy volunteers. The study was approved by the local Ethical Committee (049.07.08). Results: IBD patients had a significantly (p<0.01) slower gastric emptying (t1⁄2= 243.9 ± 14.2 min) than the controls (t1⁄2= 174.1 ± 6.3 min). IBD patients with dyspepsia (t1⁄2=265.9 ± 21.7 min, N=14) had significantly (p<0.05) prolonged gastric emptying when compared to IBD patients without dyspeptic symptoms (t1⁄2= 220.2 ± 16.1 min, N=13). Leptin (25.9 ± 5.8 ng/ml), but not active ghrelin (28.5 ± 2.4 pg/ml), was significantly (p<0.05) higher in IBD patients with dyspepsia than in IBD patients without dyspepsia (leptin= 13.7 ± 3.4 ng/ml, ghrelin=33.2 ± 6.0 pg/ml). In IBD patients with dyspepsia, only vomiting had positive linear correlation with gastric emptying (t1⁄2) (p=0.03) and leptin levels (p=0.06). No difference between the subgroups of patients with respect to type of disease (Crohn or ulcerative colitis), gender or age was found. However, the group with dyspepsia had more patients with active diseases than the group without dyspepsia (p<0.01). Conclusion: In IBD patients, dyspeptic symptoms, particularly vomiting, were associated with prolonged gastric emptying, high leptin serum levels and the presence of disease activity. The clinical relevance of the present findings remains to be demonstrated. Financial support: Capes, CNPq.

High plasma ghrelin protects from coronary heart disease and Leu72Leu polymorphism of ghrelin gene from cancer in healthy adults during the 19 years follow-up study

The aim of our investigation was to find out if ghrelin concentrations or polymorphisms predict the future risk for cardiovascular diseases and cancer in a population-based cohort initiated in 1991 (491 hypertensive and 513 control subjects). Total mortality and hospital events were followed up for 19 years. Fasting total ghrelin concentrations were determined and Arg51Gln, Leu72Met and −501A>C polymorphisms identified. Cox regression analysis was performed. The mean value in the control cohort was 674pg/ml whereas in the hypertensive cohort it was 661pg/ml. The associations found suggest that in the controls the highest ghrelin quartile protected from CHD (coronary heart disease). The results were significant without or with adjustments for age, sex, smoking, systolic blood pressure and LDL cholesterol, BMI, type 2 diabetes or QUICK index. C/C variant of the promoter associated with the prevention of IHD (ischemic heart disease) in the hypertensive group (p<0.05). The controls with the Leu72Leu genotype had less cancer (p<0.05). In conclusion, high plasma ghrelin concentration was related to protection from CHD and Leu72Leu genotype to prevention of cancer in healthy adults during the 19 years follow-up. C/C promoter protects from IHD in the hypertensive subjects.

Gut hormone activity of children born to women with and without gestational diabetes

What is already known about this subject Children born to women with gestational diabetes have greater risk for obesity. Obesity in adults and children is associated with blunted postprandial gut hormone responses. What this study adds Children of women with gestational diabetes have a blunted postprandial response of GLP-1. Children of women with gestational diabetes have high fasting PYY concentrations. Intrauterine exposure to gestational diabetes mellitus (GDM) increases risk for obesity. Obesity is associated with a blunted postprandial gut hormone response, which may impair satiety and thereby contribute to weight gain. The postprandial response of gut hormones among children of women with GDM has not previously been investigated. To examine whether children of women with GDM have suppressed peptide-tyrosine-tyrosine (PYY) and glucagon-like-peptide-1 (GLP-1), and higher concentrations of ghrelin, following a meal challenge. A secondary objective was to investigate associations of these hormones with children's free-living energy intake. Children (n = 42) aged 5-10 years were stratified into two groups: offspring of GDM mothers (OGD) and of non-diabetic mothers (CTRL). Body composition was measured by dual-energy X-ray absorptiometry, and circulating PYY, GLP-1 and total ghrelin were measured during a liquid meal challenge. Energy intake was assessed by three 24-h diet recalls. Between-groups analyses of fasting and incremental area under the curve (AUC) found no differences in ghrelin. Incremental AUC for GLP-1 was greater among the CTRL vs. OGD (P < 0.05), and fasting PYY, but not incremental AUC, was higher among OGD vs. CTRL (P < 0.01). Associations of fasting and incremental AUC for each gut hormone with children's usual energy intake did not differ significantly by group. Further research is needed to more fully examine the potential role of postprandial GLP-1 suppression and high-fasting PYY concentrations on the feeding behaviour and risk for obesity among children exposed to GDM in utero.

Ghrelin, leptin and insulin in cirrhotic children and adolescents: Relationship with cirrhosis severity and nutritional status

ObjectiveGhrelin, leptin, and insulin concentrations are involved in the control of food intake and they seem to be associated with anorexia–cachexia in cirrhotic patients. The present study aimed to investigate the relationship between the nutritional status and fasting ghrelin, leptin and insulin concentrations in pediatric cirrhotic patients. MethodsThirty-nine patients with cirrhosis and 39 healthy controls aged 0–15years matched by sex and age were enrolled. Severity of liver disease was assessed by Child–Pugh classification, and Pediatric for End Stage Liver Disease (PELD) or Model for End-stage Liver Disease (MELD) scores. Blood samples were collected from patients and controls to assay total ghrelin, acyl ghrelin, leptin and insulin by using a commercial ELISA kit. Anthropometry parameters used were standard deviation score of height-for-age and triceps skinfold thickness-for-age ratio. A multiple linear regression analysis was used to determine the correlation between dependent and independent variables. ResultsAcyl ghrelin was significantly lower in cirrhotic patients than in controls [142 (93–278) pg/mL vs 275 (208–481) pg/mL, P=0.001]. After multiple linear regression analysis, total ghrelin and acyl ghrelin showed an inverse correlation with age; acyl ghrelin was associated with the severity of cirrhosis and des-acyl ghrelin with PELD or MELD scores ≥15. Leptin was positively correlated with gender and anthropometric parameters. Insulin was not associated with any variable. ConclusionLow acyl ghrelin and high des-acyl ghrelin concentrations were associated with cirrhosis severity, whereas low leptin concentration was associated with undernourishment in children and adolescents with cirrhosis.

High fasting ghrelin concentrations are related to low fatty acid flux in overweight subjects

Ghrelin plays a role in glucose metabolism. Given the competitive interaction between free fatty acids (FFA) and glucose as fuel sources, the present study determined relationships between acylghrelin and postprandial metabolism in overweight, nondiabetic Hispanic and African American men and women (n=19, BMI 34.8 ± 6.7 kg/m2, 47.1 ± 9.3 yrs). Subjects were admitted for 24 h and consumed a 40g‐fat meal test. Blood metabolite and hormones profiles were determined biochemically, substrate oxidation by indirect calorimetry, insulin sensitivity by IVGTT, and FFA flux by stable isotope infusion and GC/MS. Fasting ghrelin was negatively correlated with fasting insulin (r = −0.47, P = 0.04) and FFA flux (r = −0.55, P = 0.03); it tended to be positively related to glucose oxidation (r = +0.46, P = 0.06). After the meal, the absolute fall in ghrelin correlated with fasting ghrelin (r = +0.88, P &lt; 0.001) suggesting a biological limit of activity. The % decrease in ghrelin correlated positively with insulin sensitivity (r = +0.47, P = 0.04) and fasting TG (r = +0.53, P = 0.02). These data suggest that in overweight subjects, high fasting ghrelin signals efficient glucose use, lower FFA flux, and allows for greater postprandial ghrelin reduction. The connection between ghrelin and fasting FFA flux and TG suggests its role in body weight regulation is mediated through FFA metabolism, as well as though glucose metabolism.

Plasma Leptin, Ghrelin and Indexes of Glucose and Lipid Metabolism in Relation to the Appearance of Post‐Weaning Oestrus in Mediterranean Obese Sows (Iberian Pig)

Iberian pig is the most abundant Mediterranean swine. The lack of knowledge of the reproductive physiology of Mediterranean genotypes, with predisposition to obesity, led us to evaluate the influence of body condition and metabolic status at weaning on the resumption of follicular growth and the appearance of post-weaning oestrus. Females failing to display post-weaning oestrus showed a high decrease in backfat mass during lactation; backfat depth at weaning was therefore lower than in sows becoming in oestrus. Females not bearing oestrus behaviour showed lower plasma leptin levels and higher ghrelin concentrations at weaning. Moreover, these sows evidenced dyslipidemic profile (increased triglyceridemia and cholesterolemia) and mobilization of fat reserves. Hence, changes in metabolic regulation of Iberian pigs may originate large effects on the resumption of ovulatory activity after weaning.

Hormonal, hypothalamic and striatal responses to reduced body weight gain are attenuated in anorectic rats bearing small tumors

Lack of compensatory or even reduced food intake is frequently observed in weight-losing cancer patients and contributes to increased morbidity and mortality. Our previous work has shown increased transcription factor expression in the hypothalamus and ventral striatum of anorectic rats bearing small tumors. mRNA expression of molecules known to be involved in pathways regulating appetite in these structures was therefore assessed in this study. Given that pain, pro-inflammatory cytokines and metabolic hormones can modify food intake, spinal cord cellular activation patterns and plasma concentrations of cytokines and hormones were also studied. Morris hepatoma 7777 cells injected subcutaneously in Buffalo rats provoked a 10% lower body weight and 15% reduction in food intake compared to free-feeding tumor-free animals 4weeks later when the tumor represented 1–2% of body mass. No differences in spinal cord activation patterns or plasma concentration of pro-inflammatory cytokines were observed between groups. However, the changes in plasma ghrelin and leptin concentrations found in food-restricted weight-matched rats in comparison to ad libitum-fed animals did not occur in anorectic tumor-bearing animals. Real-time PCR showed that tumor-bearing rats did not display the increase in hypothalamic agouti-related peptide mRNA observed in food-restricted weight-matched animals. In addition, microarray analysis and real-time PCR revealed increased ventral striatal prostaglandin D synthase expression in food-restricted animals compared to anorectic tumor-bearing rats. These findings indicate that blunted hypothalamic AgRP mRNA expression, probably as a consequence of relatively high leptin and low ghrelin concentrations, and reduced ventral striatal prostaglandin D synthesis play a role in maintaining cancer-associated anorexia.