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Sample records for plasma total ghrelin

  1. Sequencing analysis of ghrelin gene 5' flanking region: relations between the sequence variants, fasting plasma total ghrelin concentrations, and body mass index.

    Science.gov (United States)

    Vartiainen, Johanna; Kesäniemi, Y Antero; Ukkola, Olavi

    2006-10-01

    Ghrelin is a 28-amino-acid peptide with several functions linked to energy metabolism. Low ghrelin plasma concentrations are associated with obesity, hypertension, and type 2 diabetes mellitus, whereas high concentrations reflect states of negative energy balance. Several studies addressing the hormonal and neural regulation of ghrelin gene expression have been carried out, but the role of genetic factors in the regulation of ghrelin plasma levels remains unclear. To elucidate the role of genetic factors in the regulation of ghrelin expression, we screened 1657 nucleotides of the ghrelin gene 5' flanking region (promoter and possible regulatory sites) for new sequential variations from patient samples with low (n = 50) and high (n = 50) fasting plasma total ghrelin concentrations (low- and high-ghrelin groups). Eleven single nucleotide polymorphisms (SNPs), 3 of which were rare variants (allelic frequency less than 1%) were found in our population. The genotype distribution patterns of the SNPs did not differ between the study groups, except for SNP-501A>C (P = .039). In addition, the SNP-01A>C was associated with body mass index (BMI) (P = .018). This variant was studied further in our large and well-defined Oulu Project Elucidating Risk for Atherosclerosis (OPERA) cohort (n = 1045) by the restriction fragment length polymorphism (RFLP) technique. No significant association of SNP-501A>C genotypes with fasting ghrelin plasma concentrations was found in the whole OPERA population. However, the association of this SNP with BMI and with waist circumference reached statistical significance in OPERA (P = .047 and .049, respectively), remaining of borderline significance for BMI after adjustments (P = .055). The results indicate that factors other than the 11 SNPs found in this study in the 5' flanking region of ghrelin gene are the main determinants of ghrelin plasma levels. However, SNP-501 A>C genotype distribution seems to be different in subjects having the highest

  2. Dose-dependent response of plasma ghrelin and growth hormone concentrations to bovine ghrelin in Holstein heifers.

    Science.gov (United States)

    ThidarMyint, Hnin; Yoshida, Hiroko; Ito, Tetsuya; Kuwayama, Hideto

    2006-06-01

    The stimulatory effect of the novel gastric-derived hormone, ghrelin, on growth hormone (GH) secretion has been reported in domestic animals as well as in humans and rats. The octanoyl modification on the Ser3 residue of ghrelin appears to be essential for its endocrine activity. A major portion of circulatory ghrelin lacks acylation but possesses some biological activities other than GH stimulation; therefore, both types of acylated and des-acyl ghrelin are supposed to be important for energy homeostasis. The effects of pharmacological doses of rat and/or human ghrelin on GH secretion have been reported recently in ruminants; however, the physiological effect of exogenous bovine ghrelin on its own plasma level and on GH secretion is still unknown. Moreover, the RIA systems for the measurement of bovine active ghrelin and for bovine total ghrelin including acylated ghrelin, des-acyl ghrelin and all ghrelin peptides with an intact bovine C-terminal have not yet been validated. In this study, we established the RIA system for bovine ghrelin, and the dose-dependent effects of synthesized acylated bovine ghrelin(1-27) on plasma active and total ghrelin, GH, insulin and metabolites were measured in Holstein heifers. Six animals were intravenously injected with synthesized acylated bovine ghrelin (0, 0.1, 0.5, 1.0, 5.0, 10.0 microg/kg body weight (BW)) and plasma hormone concentrations were measured from serially collected samples. Bovine ghrelin RIA showed that the basal level of total ghrelin is approximately 16 times higher than that of active ghrelin in bovine plasma. Both forms of ghrelin were increased in a dose-dependent manner in response to bovine ghrelin injections, peak values were reached at 5 min after administration and returned to pre-injected values within 15 min. Plasma GH was responsive to all doses of bovine ghrelin in a dose-dependent manner, peaked as early as at 5-10 min after injection and returned to the basal value within 60 min. The GH area

  3. Plasma total ghrelin and leptin levels in human narcolepsy and matched healthy controls: Basal concentrations and response to sodium oxybate

    NARCIS (Netherlands)

    Donjacour, C.E.; Pardi, D.; Aziz, N.A.; Frolich, M.; Roelfsema, F.; Overeem, S.; Pijl, H.; Lammers, G.J.

    2013-01-01

    STUDY OBJECTIVES: Narcolepsy is caused by a selective loss of hypocretin neurons and is associated with obesity. Ghrelin and leptin interact with hypocretin neurons to influence energy homeostasis. Here, we evaluated whether human hypocretin deficiency, or the narcolepsy therapeutic agent sodium oxy

  4. Plasma levels of acylated ghrelin in patients with functional dyspepsia

    Institute of Scientific and Technical Information of China (English)

    Yeon Soo Kim; Joon Seong Lee; Tae Hee Lee; Joo Young Cho; Jin Oh Kim; Wan Jung Kim; Hyun Gun Kim; Seong Ran Jeon; Hoe Su Jeong

    2012-01-01

    AIM:To investigate the relationship between plasma acylated ghrelin levels and the pathophysiology of functional dyspepsia.METHODS:Twenty-two female patients with functional dyspepsia and twelve healthy volunteers were recruited for the study.The functional dyspepsia patients were each diagnosed based on the Rome Ⅲ criteria.Eligible patients completed a questionnaire concerning the severity of 10 symptoms.Plasma acylated ghrelin levels before and after a meal were determined in the study participants using a commercial human acylated enzyme immunoassay kit; electrogastrograms were performed for 50 min before and after a standardized 10-min meal containing 265 kcal.RESULTS:There were no significant differences in plasma acylated ghrelin levels between healthy volunteers and patients with functional dyspepsia.However,in patients with functional dyspepsia,there was a negative correlation between fasting plasma acylated ghrelin levels and the sum score of epigastric pain (r =-0.427,P =0.047) and a positive correlation between the postprandial/fasting plasma acylated ghrelin ratio and the sum score of early satiety (r =0.428,P =0.047).Additionally,there was a negative correlation between fasting acylated ghrelin plasma levels and fasting normogastria (%) (r =-0.522,P =0.013).Interestingly,two functional dyspepsia patients showed paradoxically elevated plasma acylated ghrelin levels after the meal.CONCLUSION:Abnormal plasma acylated ghrelin levels before or after a meal may be related to several of the dyspeptic symptoms seen in patients with functional dyspepsia.

  5. Dietary Caprylic Acid (C8:0) Does Not Increase Plasma Acylated Ghrelin but Decreases Plasma Unacylated Ghrelin in the Rat.

    Science.gov (United States)

    Lemarié, Fanny; Beauchamp, Erwan; Dayot, Stéphanie; Duby, Cécile; Legrand, Philippe; Rioux, Vincent

    2015-01-01

    Focusing on the caprylic acid (C8:0), this study aimed at investigating the discrepancy between the formerly described beneficial effects of dietary medium chain fatty acids on body weight loss and the C8:0 newly reported effect on food intake via ghrelin octanoylation. During 6 weeks, Sprague-Dawley male rats were fed with three dietary C8:0 levels (0, 8 and 21% of fatty acids) in three experimental conditions (moderate fat, caloric restriction and high fat). A specific dose-response enrichment of the stomach tissue C8:0 was observed as a function of dietary C8:0, supporting the hypothesis of an early preduodenal hydrolysis of medium chain triglycerides and a direct absorption at the gastric level. However, the octanoylated ghrelin concentration in the plasma was unchanged in spite of the increased C8:0 availability. A reproducible decrease in the plasma concentration of unacylated ghrelin was observed, which was consistent with a decrease in the stomach preproghrelin mRNA and stomach ghrelin expression. The concomitant decrease of the plasma unacylated ghrelin and the stability of its acylated form resulted in a significant increase in the acylated/total ghrelin ratio which had no effect on body weight gain or total dietary consumption. This enhanced ratio measured in rats consuming C8:0 was however suspected to increase (i) growth hormone (GH) secretion as an increase in the GH-dependent mRNA expression of the insulin like growth Factor 1 (IGF-1) was measured (ii) adipocyte diameters in subcutaneous adipose tissue without an increase in the fat pad mass. Altogether, these results show that daily feeding with diets containing C8:0 increased the C8:0 level in the stomach more than all the other tissues, affecting the acylated/total ghrelin plasma ratio by decreasing the concentration of circulating unacylated ghrelin. However, these modifications were not associated with increased body weight or food consumption.

  6. Plasma Ghrelin Levels Are Associated with Anorexia but Not Cachexia in Patients with NSCLC

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    Blauwhoff-Buskermolen, Susanne; Langius, Jacqueline A. E.; Heijboer, Annemieke C.; Becker, Annemarie; de van der Schueren, Marian A. E.; Verheul, Henk M. W.

    2017-01-01

    Background and Aims: The ghrelin receptor is one of the new therapeutic targets in the cancer anorexia-cachexia syndrome. Previous studies revealed that plasma ghrelin levels were high in patients with anorexia nervosa and low in obese subjects. We studied to what extent ghrelin levels are related with anorexia and cachexia in patients with cancer. Materials and Methods: Fasted ghrelin levels were determined as well as anorexia and cachexia in patients with stage III/IV non-small cell lung cancer before chemotherapy. Total plasma ghrelin was measured by radioimmunoassay. Anorexia was measured with the FAACT-A/CS questionnaire (cut-off value ≤ 37). Cachexia was determined as >5% weight loss (WL) in 6 months or >2% WL in 6 months in combination with low BMI or low muscle mass. The Kruskal-Wallis test was performed to assess differences in plasma ghrelin levels between four groups: patients with (+) or without (−) anorexia (A) or cachexia (C). Multiple regression analyses were performed to assess differences in plasma ghrelin levels between patients C+ and C− and patients with A+ and A− (adjusted for age and sex). Results: Forty patients with stage III (33%) or stage IV (68%) were recruited, of which 50% was male. Mean age was 59.6 ± 10.3 years. Sixteen patients had no anorexia or cachexia (A−C−), seven patients had both anorexia and cachexia (A+C+), ten patients had anorexia without cachexia (A+C−) and seven patients had cachexia without anorexia (A−C+). The levels of total plasma ghrelin were significantly different between the four groups of patients with or without anorexia or cachexia (p = 0.032): the A+C− patients had significantly higher ghrelin levels [median (IQR): 1,754 (1,404–2,142) compared to the A−C+ patients 1,026 (952–1,357), p = 0.003]. A+ patients had significantly higher ghrelin levels compared A− patients (C+ and C− combined, β: 304, p = 0.020). Plasma ghrelin levels were not significantly different in C+ patients

  7. Impaired postprandial fullness in Type 2 diabetic subjects is rescued by acute exercise independently of total and acylated ghrelin.

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    Knudsen, Sine H; Karstoft, Kristian; Solomon, Thomas P J

    2013-09-01

    Ghrelin levels are suppressed in obese subjects and subjects with Type 2 diabetes mellitus (T2DM). Exercise-stimulated decreases in plasma ghrelin are a proposed mediator of exercise-induced satiety in healthy subjects. However, exercise-induced satiety and the impact of impaired ghrelin levels in obesity-related disease are poorly understood. Therefore our objective was to investigate exercise-induced postprandial satiety and ghrelin responses in overweight subjects with T2DM (N = 8) and healthy controls (N = 7). Visual analog scale satiety questionnaires (assessing hunger, thirst, food that could be eaten, nausea, and fullness) and circulating levels of glucose, insulin, and total and acylated ghrelin were measured at baseline and in response to a 75 g oral glucose load, provided immediately after an aerobic exercise bout (1 h at 50% Wmax) or no exercise (rest trial), on two separate occasions. Baseline levels of total (284.4 ± 15.9 and 397.6 ± 35.2 pmol/l) and acylated ghrelin (7.9 ± 1.0 and 13.7 ± 1.2 pmol/l) were lower in subjects with T2DM compared with healthy subjects (P Exercise increased postprandial fullness in the T2DM group (P ghrelin levels were unaffected. Our data suggest that the presence of T2DM likely drives suppressed ghrelin levels and poor appetite regulation, but a single exercise bout is sufficient to restore oral glucose-induced fullness independently of ghrelin.

  8. Regular physical activity influences plasma ghrelin concentration in adolescent girls.

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    Jürimäe, Jaak; Cicchella, Antonio; Jürimäe, Toivo; Lätt, Evelin; Haljaste, Kaja; Purge, Pritt; Hamra, Jena; von Duvillard, Serge P

    2007-10-01

    We examined the effect of regular physical activity on plasma ghrelin concentration after onset of puberty in girls. In addition, we also examined the association of fasting plasma ghrelin concentration with various plasma biochemical, body composition, and aerobic capacity variables in healthy adolescent girls. Fifty healthy schoolgirls ages 11 to 16 yr were divided either into a physically active (N = 25) or a physically inactive (N = 25) group. The physically active group consisted of swimmers who had trained on an average of 6.2 +/- 2.0 h.wk(-1) for the last 2 yr, whereas the inclusion criterion for the physically inactive group was the participation in physical education classes only. The subjects were matched for age (+/- 1 yr) and body mass index (BMI; +/- 2 kg.m(-2)). Maturation I group (14 matched pairs) included pubertal stages 2 and 3, and maturation II group (11 matched pairs) included pubertal stages 4 and 5. Physically active girls had significantly higher (P ghrelin levels than the physically inactive girls (maturation I: 1152.1 +/- 312.9 vs 877.7 +/- 114.8 pg.mL(-1); maturation II: 1084.0 +/- 252.5 vs 793.4 +/- 164.9 pg.mL(-1)). Plasma ghrelin concentration was negatively related to percent body fat, fat mass, peak oxygen consumption per kilogram of body mass, leptin, estradiol, insulin, and insulin-like growth factor-I (IGF-I) (r > -0.298; P ghrelin concentration using the variables that were significantly associated with ghrelin concentration demonstrated that plasma IGF-I was the most important predictor of plasma ghrelin concentration (beta = -0.396; P = 0.008). Regular physical activity influences plasma ghrelin concentrations in girls with different pubertal maturation levels. Plasma IGF-I concentration seems to be the main determinant of circulating ghrelin in healthy, normal-weight adolescent girls.

  9. Factors associated with fasting plasma ghrelin levels in children and adolescents

    Institute of Scientific and Technical Information of China (English)

    Chao-Chun Zou; Li Liang; Zheng-Yan Zhao

    2008-01-01

    AIM:To measure plasma ghrelin levels in children and adolescents,analyze the associated factors,and investigate the role of ghrelin in obesity,insulin resistance and reproductive physiology.METHODS:A total of 283 subjects aged 4.8-15.8 year were enrolled.Fasting blood samples were collected and plasma ghrelin levels were measured by radioimmunoassay.Fasting glucose (FG),fasting insulin (FI),baseline testosterone (T),estradiol (E2),prolactin (PRL),luteinizing hormone (LH),follicle-stimulating hormone (FSH),serum total cholesterol (TC),triglyceride (TG),alanine aminotransferase (ALT) and uric acid (UA) were measured.Body mass index (BMI),insulin resistance by homeostasis model (HOMA-IR) and beta cell function by homeostasis model (HOMA-β) were calculated.RESULTS:The median ghrelin level was 290 ng/L (15.0-1325.0 ng/i).Bivariate correlation analysis showed that ghrelin levels were inversely correlated with BMI,ALT,TG,UA,LH,FI and HOMA-IR (all P<0.05).No other significant correlation was found between ghrelin levels and age,gender,TC,E2,FSH,PRL,FG and HOMA-β.Stepwise multiple regression analysis showed that only BMI and FI were independent determinants of plasma ghrelin levels in these children and adolescents (P = 0.018 and P = 0.046,respectively),which explained 25.4% of the variance.CONCLUSION:These data suggest that the lower ghrelin levels in obese subjects may be the result of obesity and hyperinsulinemia,which is very common in obese subjects.Moreover,ghrelin may regulate human reproductive physiology indirectly.

  10. Total and acylated ghrelin levels in children with poor growth.

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    Pinsker, Jordan E; Ondrasik, Deborah; Chan, Debora; Fredericks, Gregory J; Tabisola-Nuesca, Eludrizza; Fernandez-Aponte, Minela; Focht, Dean R; Poth, Merrily

    2011-06-01

    Ghrelin, an enteric hormone with potent appetite stimulating effects, also stimulates growth hormone release. We hypothesized that altered levels of total ghrelin (TG) or acylated ghrelin (AG) could affect growth by altering growth hormone secretion, subsequently affecting insulin-like growth factor-1 (IGF-1) generation or by altering appetite and food intake. After institutional review board approval, 52 children presenting for evaluation of chronic gastrointestinal symptoms (group 1), poor weight gain (group 2), or poor linear growth (group 3) were evaluated for fasting TG and AG levels in addition to their regular evaluation. Serum ghrelin, IGF-1, and prealbumin were compared between groups. No difference was observed for mean fasting TG between groups. However, mean fasting AG was highest in patients in group 2 (465 ± 128 pg/mL) versus group 1 (176 ± 37 pg/mL) and group 3 (190 ± 34 pg/mL). IGF-1 was lowest in patients in group 2 despite similar prealbumin levels among the three groups. We conclude that serum AG levels are highest in children with isolated poor weight gain compared with children with short stature or chronic gastrointestinal symptoms, suggesting the possibility of resistance to AG in underweight children. Additional studies are needed to further clarify ghrelin's role in growth and appetite.

  11. Prognostic Significance of Preoperative and Postoperative Plasma Levels of Ghrelin in Gastric Cancer: 3-Year Survival Study

    Science.gov (United States)

    Soleyman-Jahi, Saeed; Abdirad, Afshin; Fallah, Amir Afraz; Ghasemi, Sevil; Sadeghi, Fatemeh; Heidari, Reza; Mahmoodzadeh, Habibollah; Zendehdel, Kazem

    2017-01-01

    OBJECTIVES: We aimed to investigate prognostic effects of plasma levels of ghrelin before and after gastrectomy in gastric cancer (GC). METHODS: We followed 81 GC patients up to 3 years in this study. They were candidates for curative gastrectomy with or without neoadjuvant chemotherapy. Plasma levels of total and active ghrelins before and after the operation were assessed. Association of plasma levels of ghrelin with survival were assessed and adjusted for other potential prognostic factors using Cox regression analyses. RESULTS: Both total and active ghrelins dropped after gastrectomy (Pcachexia (HR=2.99, 95% CI: 1.35–6.63), and receiving no neoadjuvant chemotherapy (HR=2.02, 95% CI: 1.04–3.92) were other poor prognostic factors. CONCLUSIONS: Preoperative and postoperative plasma levels of ghrelin could predict survival of GC patients with different patterns. This prognostic effect was independent of stage and cachexia. Measurement of plasma ghrelin in GC patients could complement conventional staging for more precise risk-stratification of the patients. Extrinsic admirations of ghrelin after total gastrectomy has potentials to improve survival of GC patients. PMID:28055030

  12. Different responses in postprandial plasma ghrelin and GH levels induced by concentrate or timothy hay feeding in wethers.

    Science.gov (United States)

    Takahashi, T; Kobayashi, Y; Hasegawa, S; Touno, E; Otani, Y; Haga, S; Itoh, F; Katoh, K; Obara, Y

    2008-05-01

    Ghrelin and growth hormone (GH) play a key role in regulating energy balance, metabolic hormone secretion and food intake. Ghrelin and GH responses to dietary compositions have not yet been fully clarified, although there may be significant relationships between dietary compositions and ghrelin and GH responses. In the present study, therefore, we assessed whether dietary compositions influence postprandial plasma ghrelin and GH levels in wethers. Four wethers were respectively fed concentrate (C) or timothy hay (R) for 14 days. The levels of total digestive nutrients (TDN) and crude protein (CP) were adjusted to be at the same level. The basal ghrelin in both groups was rapidly and significantly decreased after feeding. Although the decline of ghrelin levels in C was greater and shorter than that in R, no significant difference was observed in the area under the curve (AUC) or in the incremental area. The plasma GH levels were also rapidly and significantly decreased after feeding in both groups and a significant difference was observed between the two groups for AUC of GH. Interestingly, the circadian changes in the plasma ghrelin levels were close to those in the GH levels in C, but this was not the case in R. These data suggest that dietary compositions influence postprandial plasma ghrelin and GH levels, and that these differences may be caused by several factors, including nutrients and ruminal fermentation.

  13. Plasma leptin and ghrelin concentrations in patients with Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Yoshito Nishi; Hajime Isomoto; Hiroaki Ueno; Ken Ohnita; Chun Yang Wen; Fuminao Takeshima; Ryosuke Mishima; Masamitsu Nakazato; Shigeru Kohno

    2005-01-01

    AIM: To determine the concentrations of leptin and ghrelin, which have opposite effects on appetite,energy expenditure, and weight control, in the plasma of patients with Crohn's disease (CD), which is often associated with weight loss and malnutrition.METHODS: Plasma leptin and ghrelin concentrations were determined in 28 outpatients with CD by radioimmunoassay. Age- and sex-matched controls with and without Helicobacter pylori(H pylori) infection (28for each) were enrolled in the study. Circulating levels of these hormones were assessed with respect to CD activity, disease localization and medical treatment.RESULTS: There were no significant differences in ghrelin levels between CD patients and H pylorinegative controls. However, circulating ghrelin levels were significantly lower in H pylori-infected subjects than in CD patients and uninfected controls. Plasma leptin levels were comparable among the groups. Localization and medication profile had no significant impact on circulating ghrelin and leptin levels.CONCLUSION: Apart from H pyloriinfection, CD itself has no significant influence on circulating ghrelin and leptin levels in the outpatients who were mostly in inactive state.

  14. Dietary Caprylic Acid (C8:0 Does Not Increase Plasma Acylated Ghrelin but Decreases Plasma Unacylated Ghrelin in the Rat.

    Directory of Open Access Journals (Sweden)

    Fanny Lemarié

    Full Text Available Focusing on the caprylic acid (C8:0, this study aimed at investigating the discrepancy between the formerly described beneficial effects of dietary medium chain fatty acids on body weight loss and the C8:0 newly reported effect on food intake via ghrelin octanoylation. During 6 weeks, Sprague-Dawley male rats were fed with three dietary C8:0 levels (0, 8 and 21% of fatty acids in three experimental conditions (moderate fat, caloric restriction and high fat. A specific dose-response enrichment of the stomach tissue C8:0 was observed as a function of dietary C8:0, supporting the hypothesis of an early preduodenal hydrolysis of medium chain triglycerides and a direct absorption at the gastric level. However, the octanoylated ghrelin concentration in the plasma was unchanged in spite of the increased C8:0 availability. A reproducible decrease in the plasma concentration of unacylated ghrelin was observed, which was consistent with a decrease in the stomach preproghrelin mRNA and stomach ghrelin expression. The concomitant decrease of the plasma unacylated ghrelin and the stability of its acylated form resulted in a significant increase in the acylated/total ghrelin ratio which had no effect on body weight gain or total dietary consumption. This enhanced ratio measured in rats consuming C8:0 was however suspected to increase (i growth hormone (GH secretion as an increase in the GH-dependent mRNA expression of the insulin like growth Factor 1 (IGF-1 was measured (ii adipocyte diameters in subcutaneous adipose tissue without an increase in the fat pad mass. Altogether, these results show that daily feeding with diets containing C8:0 increased the C8:0 level in the stomach more than all the other tissues, affecting the acylated/total ghrelin plasma ratio by decreasing the concentration of circulating unacylated ghrelin. However, these modifications were not associated with increased body weight or food consumption.

  15. Relationship between Plasma Ghrelin Levels and Insulin Resistance and Blood Pressure in Octogenarians

    Institute of Scientific and Technical Information of China (English)

    赵荫涛; 邵莉; 滕丽莉; 张代富; 张华

    2010-01-01

    The association between fasting plasma ghrelin levels and insulin resistance and blood pressure(BP) in octogenarians was investigated in this study.A total of 487 unrelated octogenarians(including 203 men and 284 women) were enrolled in this cross-sectional study at the Healthy Care Center of Shanghai East Hospital,Tongji University,China,from October 2008 to April 2009.Plasma ghrelin was determined by using the enzyme linked immunosorbent assay(ELISA).Insulin sensitivity was assessed using the homeostasis ...

  16. Ghrelin plasma levels and appetite in peritoneal dialysis patients.

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    Aguilera, Abelardo; Cirugeda, Antonio; Amair, Ruth; Sansone, Gabriela; Alegre, Laura; Codoceo, Rosa; Bajo, M Auxiliadora; del Peso, Gloria; Díez, Juan J; Sánchez-Tomero, José A; Selgas, Rafael

    2004-01-01

    Anorexia-associated malnutrition is a severe complication that increases mortality in peritoneal dialysis (PD) patients. Ghrelin is a recently-discovered orexigenic hormone with actions in brain and stomach. We analyzed, in 42 PD patients, the possible relationship between ghrelin and appetite regulation with regard to other orexigens [neuropeptide Y (NPY), NO3] and anorexigens [cholecystokinin (CCK), leptin, glucose-dependent insulinotropic peptide (GIP), tumor necrosis factor alpha (TNFalpha)]. All orexigens and anorexigens were determined in plasma. Eating motivation was evaluated using a visual analog scale (VAS). The patients were divided into three groups: those with anorexia (n = 12), those with obesity associated with high intake (n = 12), and those with no eating behavior disorders (n = 18). A control group of 10 healthy volunteers was also evaluated. Mean plasma levels of ghrelin were high (3618.6 +/- 1533 mg/mL), with 36 patients showing values above the normal range (anorexia had lower ghrelin and NPY levels and higher peptide-C, CCK, interleukin-1 (IL-1), TNFalpha, and GIP levels than did the other patients. Patients with anorexia also had an early satiety score and low desire and pleasure in eating on the VAS and diet survey. We observed significant positive linear correlations between ghrelin and albumin (r = 0.43, p anorexia show relatively lower ghrelin plasma levels than the levels seen in obese patients or in patients with normal appetite. The role of ghrelin in appetite modulation is altered in uremic PD patients, and that alteration is possibly associated with disorders in insulin and growth hormone metabolism.

  17. Plasma Ghrelin Concentrations Were Altered with Oestrous Cycle Stage and Increasing Age in Reproductively Competent Wistar Females

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    Saffrey, M. Jill; Taylor, Victoria J.

    2016-01-01

    Changes in appetite occur during the ovarian cycle in female mammals. Research on appetite-regulatory gastrointestinal peptides in females is limited, because reproductive changes in steroid hormones present additional experimental factors to control for. This study aimed to explore possible changes in the orexigenic (appetite-stimulating) gastrointestinal peptide hormone ghrelin during the rodent oestrous cycle. Fed and fasted plasma and stomach tissue samples were taken from female Wistar rats (32–44 weeks of age) at each stage of the oestrous cycle for total ghrelin quantification using radioimmunoassay. Sampling occurred during the dark phase when most eating takes place in rats. Statistical analysis was by paired-samples t-test, one-way ANOVA on normally distributed data, with Tukey post-hoc tests, or Kruskal-Wallis if not. GLM univariate analysis was used to assess main effects and interactions in ghrelin concentrations in the fed or fasted state and during different stages of the ovarian cycle, with age as a covariate. No consistent fed to fasted ghrelin increases were measured in matched plasma samples from the same animals, contrary to expectations. Total ghrelin concentrations did not significantly change between cycle stages with ANOVA, in either fed or fasted plasma or in stomach tissue. This was despite significantly decreased fasted stomach contents at oestrus (P = 0.028), suggesting decreased food intake. There was however a significant interaction in ghrelin plasma concentrations between fed and fasted proestrus rats and a direct effect of age with rats over 37 weeks old having lower circulating concentrations of ghrelin in both fed and fasted states. The biological implications of altered ghrelin plasma concentrations from 37 weeks of age are as yet unknown, but warrant further investigation. Exploring peripheral ghrelin regulatory factor changes with increasing age in reproductively competent females may bring to light potential effects on

  18. Ghrelin and Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    Hiroyuki Osawa

    2008-01-01

    Ghrelin is primarily secreted from the stomach and has been implicated in the coordination of eating behavior and weight regulation. Ghrelin also plays an essential role in the mechanism of gastric mucosal defense. Thus, it is important to clarify which diseases primar-ily influence changes in plasma ghrelin concentrations. Helicobacter pylori(H pylori infection is involved in the pathogenesis of gastritis, gastric and duodenal ulcer, gastric carcinoma, and mucosa-associated lym-phoid tissue lymphorna. H pylori eradication is related to body weight change. Compared, H pylori infected and negative subjects with normal body mass index, plasma ghrelin concentration, gastric ghrelin mRNA, and the number of ghrelin producing cells in gastric mucosa are significantly lower in Hpylori injected sub-jects than in H pylori-negative controls. Plasma ghrelin concentration decreases with the progression of gastric atrophy. Impaired gastric ghrelin production in associa-tion with atrophic gastritis induced by Hpylori infection accounts for the decrease in plasma ghrelin concentra-tion. However, the ratio of plasma acylated ghrelin to total ghrelin levels is higher in patients with chronic atrophic gastritis than in healthy subjects. This may re-sult from the compensatory increase in plasma active ghrelin concentration in response to gastric atrophy. After H pylori eradication, gastric preproghrelin mRNA expression is increased nearly 4-fold in most cases. However, changes in plasma ghrelin concentrations be-fore and after H pylori cure are not associated with the gastric ghrelin production. Plasma ghrelin changes are inversely correlated with both body weight change and initial plasma ghrelin levels.

  19. Plane of nutrition affects plasma ghrelin concentrations in neonatal calves

    Science.gov (United States)

    Investigating different planes of nutrition on appetite-related hormones could provide knowledge into the role of these hormones on growth performance in neonatal calves. The objective of the current study was to investigate the effects of feeding rates on ghrelin in plasma from preruminant calves....

  20. Plasma concentrations of acyl-ghrelin are associated with average daily gain and feeding behavior in grow-finish pigs.

    Science.gov (United States)

    Lents, C A; Brown-Brandl, T M; Rohrer, G A; Oliver, W T; Freking, B A

    2016-04-01

    The objectives of this study were to determine the effect of sex, sire line, and litter size on concentrations of acyl-ghrelin and total ghrelin in plasma of grow-finish pigs and to understand the relationship of plasma concentrations of ghrelin with feeding behavior, average daily gain (ADG), and back fat in grow-finish swine. Yorkshire-Landrace crossbred dams were inseminated with semen from Yorkshire, Landrace, or Duroc sires. Within 24 h of birth, pigs were cross-fostered into litter sizes of normal (N; >12 pigs/litter) or small (S; ≤ 9 pigs/litter). At 8 wk of age, pigs (n = 240) were blocked by sire breed, sex, and litter size and assigned to pens (n = 6) containing commercial feeders modified with a system to monitor feeding behavior. Total time eating, number of daily meals, and duration of meals were recorded for each individual pig. Body weight was recorded every 4 wk. Back fat and loin eye area were recorded at the conclusion of the 12-wk feeding study. A blood sample was collected at week 7 of the study to quantify concentrations of acyl- and total ghrelin in plasma. Pigs from small litters weighed more (P finish phase. Barrows spent more time eating (P < 0.001) than gilts, but the number of meals and concentrations of ghrelin did not differ with sex of the pig. Pigs from Duroc and Yorkshire sires had lesser (P < 0.0001) concentrations of acyl-ghrelin than pigs from Landrace sires, but plasma concentrations of total ghrelin were not affected by sire breed. Concentrations of acyl-ghrelin were positively correlated with the number of meals and negatively correlated with meal length and ADG (P < 0.05). A larger number of short-duration meals may indicate that pigs with greater concentrations of acyl-ghrelin consumed less total feed, which likely explains why they were leaner and grew more slowly. Acyl-ghrelin is involved in regulating feeding behavior in pigs, and measuring acyl-ghrelin is important when trying to understand the role of this hormone in

  1. Ghrelin

    Science.gov (United States)

    Müller, T.D.; Nogueiras, R.; Andermann, M.L.; Andrews, Z.B.; Anker, S.D.; Argente, J.; Batterham, R.L.; Benoit, S.C.; Bowers, C.Y.; Broglio, F.; Casanueva, F.F.; D'Alessio, D.; Depoortere, I.; Geliebter, A.; Ghigo, E.; Cole, P.A.; Cowley, M.; Cummings, D.E.; Dagher, A.; Diano, S.; Dickson, S.L.; Diéguez, C.; Granata, R.; Grill, H.J.; Grove, K.; Habegger, K.M.; Heppner, K.; Heiman, M.L.; Holsen, L.; Holst, B.; Inui, A.; Jansson, J.O.; Kirchner, H.; Korbonits, M.; Laferrère, B.; LeRoux, C.W.; Lopez, M.; Morin, S.; Nakazato, M.; Nass, R.; Perez-Tilve, D.; Pfluger, P.T.; Schwartz, T.W.; Seeley, R.J.; Sleeman, M.; Sun, Y.; Sussel, L.; Tong, J.; Thorner, M.O.; van der Lely, A.J.; van der Ploeg, L.H.T.; Zigman, J.M.; Kojima, M.; Kangawa, K.; Smith, R.G.; Horvath, T.; Tschöp, M.H.

    2015-01-01

    Background The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism. Scope of review In this review, we discuss the diverse biological functions of ghrelin, the regulation of its secretion, and address questions that still remain 15 years after its discovery. Major conclusions In recent years, ghrelin has been found to have a plethora of central and peripheral actions in distinct areas including learning and memory, gut motility and gastric acid secretion, sleep/wake rhythm, reward seeking behavior, taste sensation and glucose metabolism. PMID:26042199

  2. Increased plasma ghrelin suppresses insulin release in wethers fed with a high-protein diet.

    Science.gov (United States)

    Takahashi, T; Sato, K; Kato, S; Yonezawa, T; Kobayashi, Y; Ohtani, Y; Ohwada, S; Aso, H; Yamaguchi, T; Roh, S G; Katoh, K

    2014-06-01

    Ghrelin is a multifunctional peptide that promotes an increase of food intake and stimulates GH secretion. Ghrelin secretion is regulated by nutritional status and nutrients. Although a high-protein (HP) diet increases plasma ghrelin secretion in mammals, the mechanisms and the roles of the elevated ghrelin concentrations due to a HP diet have not been fully established. To clarify the roles of elevated acylated ghrelin upon intake of a HP diet, we investigated the regulation of ghrelin concentrations in plasma and tissues in wethers fed with either the HP diet or the control (CNT) diet for 14 days, and examined the action of the elevated plasma ghrelin by using a ghrelin-receptor antagonist. The HP diet gradually increased the plasma acylated-ghrelin concentrations, but the CNT diet did not. Although the GH concentrations did not vary significantly across the groups, an injection of ghrelin-receptor antagonist enhanced insulin levels in circulation in the HP diet group. In the fundus region of the stomach, the ghrelin levels did not differ between the HP and CNT diet groups, whereas ghrelin O-acyltransferase mRNA levels were higher in the group fed with HP diet than those of the CNT diet group were. These results indicate that the HP diet elevated the plasma ghrelin levels by increasing its synthesis; this elevation strongly suppresses the appearance of insulin in the circulation of wethers, but it is not involved in GH secretion. Overall, our findings indicate a role of endogenous ghrelin action in secretion of insulin, which acts as a regulator after the consumption of a HP diet.

  3. Effect of pubertal development and physical activity on plasma ghrelin concentration in boys.

    Science.gov (United States)

    Jürimäe, J; Cicchella, A; Tillmann, V; Lätt, E; Haljaste, K; Purge, P; Pomerants, T; Jürimäe, T

    2009-01-01

    The aim of the present study was to assess the influence of regular physical activity on plasma ghrelin concentration in pre-pubertal and pubertal boys. In addition, the impact of ghrelin concentration on bone mineral density (BMD) was examined. In total, 56 healthy schoolboys aged between 10 and 16 yr were divided into the swimming (no.=28) and the control (no.=28) groups. The subjects were matched by age and body mass index (BMI), generating 9 matched pairs in pubertal group I (Tanner stage 1), 11 pairs in group II (Tanner stages 2 and 3), and 8 pairs in group III (Tanner stages 4 and 5). Swimmers in pubertal groups II and III had significantly (both pghrelin levels than the controls (group II: 1126.8+/-406.0 vs 868.3+/-411.2 pg/ml; group III: 1105.5+/-337.5 vs 850.8+/-306.0 pg/ml, respectively), whereas no difference was seen in the pubertal group I (1230.8+/-386.0 vs 1272.7+/-424.4 pg/ml). Ghrelin was the most important hormonal determinant for total BMD and lumbar apparent volumetric BMD (BMAD) (R2=27.2% and R2=19.8%, respectively) in swimmers, whereas in control boys, plasma IGF-I was the most important hormonal predictor accounting for 41.8% of the variability of total BMD and 20.4% of the variability of lumbar BMAD. In conclusion, ghrelin concentration decreased during puberty in physically inactive boys, while in regularly physically active boys it remained relatively unchanged. Ghrelin appears to be an important hormonal predictor for BMD in physically active boys, while BMD is mostly determined by IGF-I in physically inactive boys.

  4. Ghrelin

    Directory of Open Access Journals (Sweden)

    T.D. Müller

    2015-06-01

    Major conclusions: In recent years, ghrelin has been found to have a plethora of central and peripheral actions in distinct areas including learning and memory, gut motility and gastric acid secretion, sleep/wake rhythm, reward seeking behavior, taste sensation and glucose metabolism.

  5. Ghrelin

    NARCIS (Netherlands)

    T.D. Müller; R. Nogueiras; M.L. Andermann; Z.B. Andrews; S.D. Anker; J. Argente; R.L. Batterham; S.C. Benoit; C.Y. Bowers; F. Broglio (Fabio); F.F. Casanueva; D. D'Alessio; I. Depoortere; A. Geliebter; E. Ghigo (Ezio); P.A. Cole; M. Cowley; D.E. Cummings; A. Dagher (Alain); S. Diano; S.L. Dickson; C. Dieguez (Carlos); R. Granata (Riccarda); H.J. Grill; K. Grove; K.M. Habegger; K. Heppner; M.L. Heiman; L. Holsen; B. Holst; A. Inui; J.O. Jansson; H. Kirchner; M. Korbonits; B. Laferrère; C.W. LeRoux; M. Lopez; S. Morin; M. Nakazato; R. Nass; D. Perez-Tilve; P.T. Pfluger; T.W. Schwartz; R.J. Seeley; M. Sleeman; Y. Sun (Yuxiang); L. Sussel; J. Tong; M.O. Thorner; A-J. van der Lely (Aart-Jan); L.H.T. van der Ploeg; J.M. Zigman; M. Kojima; K. Kangawa; R.G. Smith (Roy); T. Horvath; M. Tschop (Matthias)

    2015-01-01

    textabstractThe gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism. Scope o

  6. Ghrelin

    DEFF Research Database (Denmark)

    Mueller, T. D.; Nogueiras, R.; Andermann, M. L.

    2015-01-01

    Background The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism. Scope...... areas including learning and memory, gut motility and gastric acid secretion, sleep/wake rhythm, reward seeking behavior, taste sensation and glucose metabolism....

  7. Plasma ghrelin in anorexia, bulimia, and binge-eating disorder: relations with eating patterns and circulating concentrations of cortisol and thyroid hormones.

    Science.gov (United States)

    Troisi, Alfonso; Di Lorenzo, Giorgio; Lega, Ilaria; Tesauro, Manfredi; Bertoli, Aldo; Leo, Roberto; Iantorno, Micaela; Pecchioli, Chiara; Rizza, Stefano; Turriziani, Mario; Lauro, Renato; Siracusano, Alberto

    2005-01-01

    The present study was designed to investigate the relations between plasma ghrelin concentrations, eating patterns, and circulating concentrations of cortisol and thyroid hormones in women with anorexia nervosa, bulimia nervosa, and binge-eating disorder. The patterns of disordered eating behavior were assessed using the Eating Attitudes Test (EAT-26) and the Bulimia Test-Revised (BULIT-R). In women with eating disorders, but not in healthy control women, plasma ghrelin concentrations were negatively correlated with body mass index (BMI) and plasma concentrations of thyreotropin (TSH), free T3 and free T4, and positively correlated with plasma concentrations of cortisol. The ghrelin concentrations of women with binge-eating and purging behavior were significantly lower than those of women with anorexia nervosa, restricting type, and there was a negative relation between the frequency and severity of binge-eating and purging behavior, as measured by the BULIT-R total score, and ghrelin concentrations. In a multivariate regression model controlling for the confounding effects of body mass index (BMI) and age, higher ghrelin concentrations were correlated with lower BULIT-R total scores. The results of this study did not confirm the hypothesis advanced in previous studies that ghrelin concentrations are higher in patients with binge-eating/purging forms of eating disorders. Based on these data, we suggest that, in women with eating disorders, ghrelin concentrations best reflect nutritional status rather than specific patterns of disordered eating behavior.

  8. Characterization of pericardial and plasma ghrelin levels in patients with ischemic and non-ischemic heart disease.

    Science.gov (United States)

    Sax, Balazs; Merkely, Béla; Túri, Katalin; Nagy, Andrea; Ahres, Abdelkrim; Hartyánszky, István; Hüttl, Tivadar; Szabolcs, Zoltán; Cseh, Károly; Kékesi, Violetta

    2013-09-10

    Ghrelin is an endocrine regulatory peptide with multiple functions including cardioprotective effects. It is produced in various tissues among others in the myocardium. Pericardial fluid has been proven to be a biologically active compartment of the heart that communicates with the myocardial interstitium. Thus, pericardial level of certain agents may reflect their concentration in the myocardium well. In our study we measured acylated (active) and total (acylated and non-acylated) pericardial and plasma ghrelin levels of patients with ischemic and non-ischemic heart disease. Pericardial fluid and plasma samples were obtained from patients with coronary artery disease (ISCH, n=54) or valvular heart disease (VHD, n=41) undergoing cardiac surgery. Acylated pericardial ghrelin concentrations were found to be significantly higher in patients with ischemic heart disease (ISCH vs. VHD, 32±3 vs. 16±2pg/ml, pheart disease as compared to non-ischemic patients suggesting an increased ghrelin production of the chronically ischemic myocardium. According to our results, pericardial ghrelin content is negatively influenced by left ventricular hypertrophy and insulin resistance.

  9. Impact of Helicobacter pylori infection on ghrelin and various neuroendocrine hormones in plasma

    Institute of Scientific and Technical Information of China (English)

    Hajime Isomoto; Hiroaki Ueno; Yoshito Nishi; Chun-Yang Wen; Masamitsu Nakazato; Shigeru Kohno

    2005-01-01

    AIM: Ghrelin, an endogenous ligand for growth hormone secretagogue receptor, influences appetite, energy balance, gastric motility and acid secretion. The stomach is the main source of circulating ghrelin. There are inconsistent reports on the influence of Helicobacter pylori (H pylori) infection on circulating ghrelin levels. We sought to elucidate the relationship between ghrelin and various peptides in plasma, with special reference to H pylori.METHODS: Plasma ghrelin levels were measured by radioimmunoassay in 89 subjects who were referred for upper gastrointestinal endoscopy, consisting of 42 H pylori infected and 47 uninfected ones. Plasma gastrin,somatostatin, leptin, insulin-like growth hormone 1 (IGF-1)and chromogranin A concentrations were also measured.Twelve patients were treated with anti- H pylori regimen.RESULTS: Ghrelin circulating levels were greatly decreased in H pylori-positive than negative individuals (194.2±90.2fmol/mL and 250.4±84.1 respectively, P<0.05), but did not significantly alter following the cure of infection (176.5±79.5 vs 191.3±120.4). There was a significant negative correlation between circulating ghrelin and leptin levels, as well as body mass index, for the whole and uninfected population, but not in H pylori-infected patients. Plasma ghrelin concentrations correlated positively with IGF-1 in H pylori-negative group and negatively with chromogranin A in the infected group.There were no significant correlations among circulating levels of ghrelin, gastrin and somatostatin irrespective of H pylori status.CONCLUSION: H pylori infection influences plasma ghrelin dynamics and its interaction with diverse bioactive peptides involved in energy balance, growth and neuroendocrine function.

  10. Plasma orexin-A and ghrelin levels in patients with chronic obstructive pulmonary disease: Interaction with nutritional status and body composition.

    Science.gov (United States)

    Akbulut, Gamze; Gezmen-Karadağ, Makbule; Ertaş, Yasemın; Uyar, Banugül Barut; Yassibaş, Emıne; Türközü, Duygu; Celebı, Ferıde; Paşaoğlu, Ozge Tuğçe; Toka, Onur; Yildiran, Hılal; Sanlier, Nevın; Köktürk, Nurdan

    2014-06-01

    Orexin-A and ghrelin are two important polypeptides that stimulate food intake, however, there is a lack of sufficient information concerning their plasma levels in patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the association between plasma orexin-A and ghrelin levels with food consumption and body composition in patients with stable phase COPD. In total, 40 patients (age, 44-80 years; male, 31; female 9) who were in the stable phase of COPD were included in the study. Blood samples for plasma orexin-A and ghrelin analysis were collected after 8-12 h of fasting; certain anthropometric measurements were obtained and a 24-h dietary recall was recorded. The mean plasma orexin-A levels in the male and female patients were 1.3±0.37 and 1.4±0.13 ng/ml, respectively, while the mean plasma ghrelin levels were 25.9±7.31 and 27.3±8.54 ng/ml, respectively. No significant correlation was observed between the body mass index and plasma orexin-A and ghrelin levels or between the plasma ghrelin levels and dietary nutrient intake (P>0.05). The plasma orexin-A levels were demonstrated to be higher in patients with a higher dietary total fibre intake (r=0.303, P=0.022). A similar correlation was observed between plasma orexin-A levels and dietary intake of soluble (r=0.033, P=0.029) and insoluble (r=0.335, P=0.024) fibre, as well as between the daily consumption of calcium and the levels of plasma orexin-A (r=0.065, P=0.046). Therefore, the results of the present study indicated that a positive correlation existed between dietary nutrient intake and plasma orexin-A levels in patients with COPD.

  11. Impaired postprandial fullness in Type 2 diabetic subjects is rescued by acute exercise independently of total and acylated ghrelin

    DEFF Research Database (Denmark)

    Knudsen, Sine H; Karstoft, Kristian; Solomon, Thomas

    2013-01-01

    Ghrelin levels are suppressed in obese subjects and subjects with Type 2 diabetes mellitus (T2DM). Exercise-stimulated decreases in plasma ghrelin are a proposed mediator of exercise-induced satiety in healthy subjects. However, exercise-induced satiety and the impact of impaired ghrelin levels...... in obesity-related disease are poorly understood. Therefore our objective was to investigate exercise-induced postprandial satiety and ghrelin responses in overweight subjects with T2DM (N = 8) and healthy controls (N = 7). Visual analog scale satiety questionnaires (assessing hunger, thirst, food that could...

  12. Effects of ghrelin injection on plasma concentrations of glucose, pancreatic hormones and cortisol in Holstein dairy cattle.

    Science.gov (United States)

    Itoh, Fumiaki; Komatsu, Tokushi; Kushibiki, Shiro; Hodate, Koichi

    2006-01-01

    Ghrelin affects not only growth hormone secretion but also nutrient utilization and metabolic hormone secretion in humans and experimental animals. The effects of ghrelin on plasma metabolic hormone and metabolite levels in domestic herbivores remain unclear despite the fact that the physiological characteristics of nutrient digestion and absorption imply specific responses to ghrelin. Therefore, the effects of ghrelin on plasma glucose, pancreatic hormones and cortisol concentrations were investigated in Holstein dairy cattle in various physiological states. Ghrelin (0.3 nmol/kg) or placebo (2% bovine serum albumin in saline) was intravenously injected in pre-ruminant calves (pre-rumen function), adult non-lactating (functional rumen) and lactating cows (functional rumen and lactation), and plasma glucose, insulin, glucagon and cortisol concentrations were then determined. Ghrelin injection increased plasma glucose concentrations in adult cows, especially in lactating cows. No hyperglycemic response was observed in pre-ruminant calves. A transient rise of insulin and glucagon levels was distinctively found in lactating cows in response to the ghrelin administration. Ghrelin injection decreased the insulin level in pre-ruminant calves. Ghrelin increased cortisol secretion independently of the physiological state. The results of the present study suggest that the effects of ghrelin on plasma glucose and pancreatic hormone levels may reflect differences in the physiological states of dairy cattle.

  13. Plasma acylated and plasma unacylated ghrelin: useful new biomarkers in patients with neuroendocrine tumors?

    Science.gov (United States)

    van Adrichem, Roxanne C S; van der Lely, Aart Jan; Huisman, Martin; Kramer, Piet; Feelders, Richard A; Delhanty, Patric J D; de Herder, Wouter W

    2016-07-01

    To date, the value of fasting plasma acylated ghrelin (AG) and unacylated ghrelin (UAG) as potential novel biomarkers in patients with neuroendocrine tumors (NETs) is unknown. The aims of this study are to (i) compare fasting AG and UAG levels between nonobese, nondiabetic NET patients (N=28) and age- (±3 years) and sex-matched nonobese, nondiabetic controls (N=28); and (ii) study the relationship between AG, UAG, and AG/UAG ratios and biochemical (chromogranin-A (CgA) and neuron-specific enolase (NSE) levels) and clinical parameters (age at diagnosis, sex, primary tumor location, carcinoid syndrome, ENETS TNM classification, Ki-67 proliferation index, grading, prior incomplete surgery) in NET patients. Fasting venous blood samples (N=56) were collected and directly stabilized with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride after withdrawal. Plasma AG and UAG levels were determined by ELISA. Expression of ghrelin was examined in tumor tissue by immunohistochemistry. There were no significant differences between NET patients and controls in AG (median: 62.5 pg/mL, IQR: 33.1-112.8 vs median: 57.2pg/mL, IQR: 26.7-128.3, P=0.66) and UAG in levels (median: 76.6pg/mL, IQR: 35.23-121.7 vs median: 64.9, IQR: 27.5-93.1, P=0.44). No significant correlations were found between AG, UAG, and AG/UAG ratios versus biochemical and clinical parameters in NET patients with the exception of age at diagnosis (AG: ρ= -0.47, P=0.012; AG/UAG ratio: ρ= -0.50, P=0.007) and baseline chromogranin-A levels (AG/UAG ratio: ρ= -0.44, P=0.019). In our view, fasting plasma acylated and unacylated ghrelin appear to have no value as diagnostic biomarkers in the clinical follow-up of patients with NETs.

  14. Leptin and ghrelin levels in colostrum, milk and blood plasma of sows and pig neonates during the first week of lactation.

    Science.gov (United States)

    Woliński, Jarosław; Słupecka, Monika; Romanowicz, Katarzyna

    2014-02-01

    Radioimmunology was used to determine leptin and ghrelin levels in sow colostrum and milk in relation to those in sow and neonatal pig blood plasma and to the body weight of piglets during the first week of lactation. The highest concentration of leptin was found in colostrum on the second day of lactation (69.3 ± 6.3 ng/mL). Leptin concentrations in sow plasma were significantly lower than in colostrum/milk (2.19 ± 0.9 ng/mL, P = 0.7692) and were stable in the first 7 days of lactation. Total and active ghrelin concentrations in colostrum/milk were stable in the measured time points (6734 ± 261 pg/mL, P = 0.3397; 831 ± 242 pg/mL, P = 0.3988, respectively). Total ghrelin concentrations in sow plasma were lower than in colostrum/milk. These results indicate that pigs follow a unique species-specific pattern of leptin and ghrelin synthesis, release and existence, and that the mammary gland is an important source of leptin and ghrelin contained in colostrum/milk.

  15. The influence of laparoscopic adjustable gastric banding and laparoscopic sleeve gastrectomy on weight loss, plasma ghrelin, insulin, glucose and lipids

    Directory of Open Access Journals (Sweden)

    Hady Razak Hady

    2012-07-01

    Full Text Available The aim of this study was to assess the impact of laparoscopic gastric banding and laparoscopic sleeve gastrectomy on the concentration of ghrelin, insulin, glucose, triglycerides, total and HDL-cholesterol, as well as AST and ALT levels in plasma in patients with obesity. The research includes 200 patients operated using LAGB (34 men average age 37.0 ± 12.6 years and 66 women average age 39.18 ± 12.17 years and LSG (48 men average age 47.93 ± 9.24 years and 52 women, 19 ± 9.33 years. The percentage of effective weight loss, effective BMI loss, concentration of ghrelin, insulin, glucose, triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, ALT, AST and HOMA IR values was taken preoperatively and at 7th day, 1 month, 3 and 6 months after surgery. Both after LSG and after LAGB, statistically significant reduction in BMI, serum insulin, glucose and HOMA IR was noticed in comparison to the preoperative values. Post LAGB, patients showed an increase of ghrelin, while LSG proved ghrelin decreased. Correlations between glucose and BMI loss, and between insulin and BMI loss in both cases are more favorable in the LSG group. Lipid parameters, AST and ALT have undergone declines or  increases in the particular time points. Both techniques cause weight loss and this way lead to changes in the concentration of ghrelin, as well as to the improvement of insulin, glucose, cholesterol and triglycerides metabolism. They reduce metabolic syndrome and multiple comorbidities of obesity.

  16. Estrogen elevates the peak overnight production rate of acylated ghrelin.

    Science.gov (United States)

    Paulo, Remberto C; Brundage, Richard; Cosma, Mihaela; Mielke, Kristi L; Bowers, Cyril Y; Veldhuis, Johannes D

    2008-11-01

    Acylated ghrelin is the putatively bioactive GH secretagogue. Estradiol (E2) stimulates the synthesis rather than inhibits the metabolic clearance of acylated ghrelin. The study took place at an academic medical center. Healthy postmenopausal women participated. Interventions included prospectively randomized, double-blind separate-day iv infusions of saline or five graded doses of ghrelin in estrogen-deficient (n=12) and E2-supplemented (n=8) women. Metabolic clearance rate (MCR), volume of distribution, half-life, and secretion rate of acylated ghrelin were assessed. In pilot iv bolus ghrelin infusions, the median half-lives of acylated and total ghrelin were 21 and 36 min (Prate (638+/-12 slope units), 2) MCR of acylated ghrelin and ghrelin infusion rate (10+/-2.5 slope units), and 3) MCR and plasma concentration of acylated ghrelin (0.017+/-0.004 slope units). These data predict peak nighttime production rates of acylated ghrelin of 3.8+/-0.9 (E2) and 1.9+/-0.2 (no E2) ng/kg.min (P=0.039). Acylated ghrelin has a multifold larger distribution volume and MCR than total ghrelin. An estrogenic milieu augments synthesis and/or acylation of ghrelin peptide without altering its MCR.

  17. The effect of exercise intensity on plasma and tissue acyl ghrelin concentrations in fasted rats.

    Science.gov (United States)

    Fathi, Rozita; Ghanbari-Niaki, Abbass; Kraemer, Robert R; Talebi-Garakani, Elahe; Saghebjoo, Marziyeh

    2010-12-10

    This study was conducted to investigate the effect of exercise training and feeding status on plasma and tissue acyl ghrelin concentrations. Thirty-two, eight-week-old male Wistar rats (185±5g) were randomly assigned to one of four groups: high intensity (HI: 34 m/min ~80-85% VO(2)max), moderate intensity (MI: 28 m/min ~70-75% VO(2)max), low intensity (LI: 20 m/min ~50-55% VO(2)max), and sedentary control (SED) groups. All experimental groups performed a 12-week exercise program consisting of treadmill running on a 0° slope for 1 h/day, 5 days/week at their respective training intensity. Twenty four hours following the last training session the animals completed a 12h fast. Rats were then killed, blood was collected and plasma separated; the fundus and soleus muscle were excised and frozen in liquid nitrogen for later analysis. Fasting levels of circulating acyl ghrelin and acyl ghrelin content in the soleus muscle and fundus, as well as glycogen in the soleus muscle were measured. Data were analyzed using one-way ANOVA. Results demonstrated that 12 weeks of exercise training combined with a 12h fast significantly increased plasma as well as soleus muscle concentrations of acyl ghrelin in the HI and MI groups (pghrelin concentrations in the fundus (pexercise training enhances fasting plasma acyl ghrelin in an intensity-dependent manner which is accompanied by a significant increase in soleus muscle and reduction in fundus acyl ghrelin levels. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. Influence of H pylori on plasma ghrelin in patients without atrophic gastritis

    Institute of Scientific and Technical Information of China (English)

    Mehmet Cindoruk; Ilhan Yetkin; Serpil Muge Deger; Tarkan Karakan; Erdal Kan; Selahattin Unal

    2007-01-01

    AIM: To determine the association between H pylori infection and serum ghrelin levels in patients without atrophic gastritis.METHODS: Fifty consecutive patients (24 males and 26 females) with either H pylori-positive gastritis (n = 34) or H pylori-negative gastritis (n = 16) with normal gastric acid secretion determined by 24-h pHmetry and without atrophic gastritis in histopathology were enrolled in this study. Thirty-four H pylori-infected patients were treated with triple therapy consisting of a daily regimen of 30 mg lansoprazole bid, 1 g amoxicillin bid and 500 mg clarithromycin bid for 14 d, followed by an additional 4 wk of 30 mg lansoprazol treatment. H pylori infection was eradicated in 23 of 34 (67.6%) patients. H pylori-positive patients were given eradication therapy. Gastric acidity was determined via intragastric pH catethers. Serum ghrelin was measured by radioimmunoassay (RIA).RESULTS: There was no significant difference in plasma ghrelin levels between H pylori -positive and H pylori-negative groups (81.10 ± 162.66 ng/L vs 76.51 ± 122.94 ng/L). In addition, there was no significant difference in plasma ghrelin levels and gastric acidity levels measured before and 3 mo after the eradication therapy.CONCLUSION: H pylori infection does not influence ghrelin secretion in patients with chronic gastritis without atrophic gastritis.

  19. Increased acylated plasma ghrelin, but improved lipid profiles 24-h after consumption of carob pulp preparation rich in dietary fibre and polyphenols.

    Science.gov (United States)

    Gruendel, Sindy; Garcia, Ada L; Otto, Baerbel; Wagner, Karen; Bidlingmaier, Martin; Burget, Lukas; Weickert, Martin O; Dongowski, Gerhard; Speth, Maria; Katz, Norbert; Koebnick, Corinna

    2007-12-01

    We have recently shown that a polyphenol-rich insoluble dietary fibre preparation from carob pulp (Ceratonia siliqua L; carob fibre) decreased postprandial acylated ghrelin, TAG and NEFA during an acute liquid meal challenge test. However, delayed effects of carob fibre consumption are unknown. Therefore, a randomized controlled crossover study in nineteen healthy volunteers consuming foods with or without 50 g carob fibre was conducted. On the subsequent day (day 2), glucose, TAG, total and acylated ghrelin as well as insulin, NEFA and leptin were assessed at baseline and at timed intervals for 300 min after ingestion of standardized bread. Consumption of carob fibre-enriched foods did not affect fasting concentrations of glucose, TAG, total ghrelin, NEFA, insulin and leptin. Fasting acylated ghrelin was increased on the day subsequent to carob fibre consumption compared with control (P = 0.046). After consumption of the standard bread on day 2, glucose response (P = 0.029) was increased, and TAG (P = 0.033) and NEFA (P carob fibre consumption the previous day. In conclusion, an increase in total and acylated plasma ghrelin accompanied by enhanced lipid metabolism after carob fibre consumption suggests higher lipid utilization and suppressed lipolysis on the day subsequent to carob fibre consumption. However, elevated glucose levels after carob fibre consumption need to be addressed in future studies.

  20. Plasma acylated and plasma unacylated ghrelin: useful new biomarkers in patients with neuroendocrine tumors?

    Directory of Open Access Journals (Sweden)

    Roxanne C S van Adrichem

    2016-07-01

    Full Text Available To date, the value of fasting plasma acylated ghrelin (AG and unacylated ghrelin (UAG as potential novel biomarkers in patients with neuroendocrine tumors (NETs is unknown.The aims of this study are to (i compare fasting AG and UAG levels between nonobese, nondiabetic NET patients (N = 28 and age- (±3 years and sex-matched nonobese, nondiabetic controls (N = 28; and (ii study the relationship between AG, UAG, and AG/UAG ratios and biochemical (chromogranin-A (CgA and neuron-specific enolase (NSE levels and clinical parameters (age at diagnosis, sex, primary tumor location, carcinoid syndrome, ENETS TNM classification, Ki-67 proliferation index, grading, prior incomplete surgery in NET patients. Fasting venous blood samples (N = 56 were collected and directly stabilized with 4-(2-aminoethyl benzenesulfonyl fluoride hydrochloride after withdrawal. Plasma AG and UAG levels were determined by ELISA. Expression of ghrelin was examined in tumor tissue by immunohistochemistry. There were no significant differences between NET patients and controls in AG (median: 62.5 pg/mL, IQR: 33.1–112.8 vs median: 57.2 pg/mL, IQR: 26.7–128.3, P = 0.66 and UAG in levels (median: 76.6 pg/mL, IQR: 35.23–121.7 vs median: 64.9, IQR: 27.5–93.1, P = 0.44. No significant correlations were found between AG, UAG, and AG/UAG ratios versus biochemical and clinical parameters in NET patients with the exception of age at diagnosis (AG: ρ = −0.47, P = 0.012; AG/UAG ratio: ρ = −0.50, P = 0.007 and baseline chromogranin-A levels (AG/UAG ratio: ρ = −0.44, P = 0.019. In our view, fasting plasma acylated and unacylated ghrelin appear to have no value as diagnostic biomarkers in the clinical follow-up of patients with NETs.

  1. Plasma ghrelin concentrations, food intake, and anorexia in liver failure.

    Science.gov (United States)

    Marchesini, Giulio; Bianchi, Giampaolo; Lucidi, Paola; Villanova, Nicola; Zoli, Marco; De Feo, Pierpaolo

    2004-05-01

    Ghrelin is related to feeding behavior and nutrition in several physiological and pathological conditions. We tested the hypothesis that the anorexia and the decreased food intake of advanced liver failure might be associated with hyperghrelinemia. Fasting ghrelin was measured in 43 cirrhotic patients, food intake was self-assessed using the Corli score and a 3-d dietary record (n = 25), and anorexia/hunger was tested by a Likert scale. Fifty healthy subjects, matched for age and body mass index, served as controls. Ghrelin levels were not systematically increased in cirrhosis (414 +/- 164 vs. 398 +/- 142 pmol/liter in controls) but increased with decreasing Corli score (P = 0.014) and along the scale of anorexia/hunger (P = 0.0001), which were both related to the 3-d dietary record (P = 0.009 and P 500 pmol/liter) was significantly associated with a low calorie intake [odds ratio (OR), 3.03 for any 100-calorie reduced intake; P = 0.015], a reduced Corli score (OR, 3.09; P = 0.031), and the anorexia score (OR, 3.37; P = 0.009), after adjustment for body mass index. The study confirms the previously observed relationship of fasting ghrelin with food intake in disease-associated malnutrition. In the presence of anorexia, hyperghrelinemia might indicate a compensatory mechanism trying to stimulate food intake, which is nonetheless ineffective in the physiological range.

  2. Effect of orlistat on the total ghrelin and leptin levels in obese patients.

    Science.gov (United States)

    Ozkan, Y; Aydin, S; Donder, E; Koca, S S; Aydin, Suna; Ozkan, B; Sahin, I

    2009-09-01

    Obesity, characterized by hyperleptinemia and hypoghrelinemia, has become a major health problem all over the world and is associated with an increased risk of complications including insulin resistance, hypertension, dyslipidemia, diabetes mellitus and atherosclerosis. The use of the pancreatic lipase inhibitor Orlistat can help seriously overweight people to achieve and maintain weight loss. The aim of our study was to compare the serum leptin and ghrelin levels in obese subjects who take orlistat with those receiving only dietary treatment. Twenty-one obese patients and 10 control subjects participated. The obese patients were divided into two groups; one group (n=11) took orlistat (120 mg, 3 times daily) and received dietary treatment and the other (n=10) only received the dietary treatment. The study lasted twelve weeks. The concentrations of serum ghrelin, leptin, insulin and C-peptide, and routine biochemical parameters, were measured in both groups. The serum ghrelin level was higher in control (183+/-62 fmol/ml) than obese (59+/-30 fmol/ml) subjects while the plasma leptin level was lower in control (8.7+/-12 microg/L) than obese (36.7+/-19 microg/L) subjects (all porlistat and dietary treatment in the obese subjects (all porlistat showed a significant change (porlistat has no effect on body weight in obese subjects additional to that conferred by a non-pharmacological life-style intervention. We therefore conclude that weight lost rather than type of treatment might be more valuable in obesity.

  3. Influence of a long-term high-fat diet on ghrelin secretion and ghrelin-induced food intake in rats.

    Science.gov (United States)

    Gomez, Guillermo; Han, Song; Englander, Ella W; Greeley, George H

    2012-01-10

    The aims of this study were: (1) to define the extent to which a high-fat (HF) diet given on a long-term basis reduces resting plasma ghrelin (total [acyl+des-acyl]) levels and the plasma ghrelin (total) response to fasting, (2) to determine whether a chronic HF diet modifies the orexigenic activity of acyl-ghrelin, (3) whether insulin pretreatment inhibits the plasma ghrelin (total) response to fasting, and (4) the extent to which pioglitazone (PIO) treatment will increase stomach and plasma ghrelin (total) levels in rats fed a HF diet. PIO is a drug given to diabetics which improves insulin resistance. Our findings show that a chronic HF diet given for either 10 or 60 weeks exerts a persistent inhibitory effect on resting plasma ghrelin (total) levels. Additionally, the plasma ghrelin (total) elevation to overnight fasting is not altered in rats fed a HF diet on a long-term basis. A HF diet does not impair the ingestive response to acyl-ghrelin. Together, these results suggest that acyl-ghrelin serves as an important orexigenic factor. Results show that insulin pretreatment does not inhibit the plasma ghrelin (total) response to fasting suggesting that meal-induced insulin secretion does not have a role in reducing ghrelin (total) secretion. In rats fed a HF diet, PIO administration increases stomach ghrelin (total) levels. Because PIO can reduce systemic glucose and lipid levels, our findings suggest that elevated glucose and lipid levels are part of the inhibitory mechanism behind reduced ghrelin (total) secretion in rats fed a HF diet.

  4. Effects of central infusion of ghrelin on food intake and plasma levels of growth hormone, luteinizing hormone, prolactin, and cortisol secretion in sheep.

    Science.gov (United States)

    Iqbal, Javed; Kurose, Yohei; Canny, Benedict; Clarke, Iain J

    2006-01-01

    Ghrelin is an endogenous ligand for the GH secretagogue/ghrelin receptor (GHS-R) and stimulates feeding behavior and GH levels in rodents and humans. A preprandial increase in plasma ghrelin levels is seen in sheep on programmed feeding, followed by a postprandial rise in plasma GH levels, but effects on food intake and endocrine function are not defined in this ruminant species. We administered ghrelin to female sheep in various modes and measured effects on voluntary food intake (VFI) and plasma levels of GH, LH, prolactin, and cortisol. Whether administered intracerebroventricularly or iv, ghrelin consistently failed to stimulate VFI. On the other hand, ghrelin invariably increased plasma GH levels and alpha,beta-diaminopropanoic acid-octanoyl3 human ghrelin was more potent than ovine ghrelin. Bolus injection of ghrelin into the third cerebral ventricle reduced plasma LH levels but did not affect levels of prolactin or cortisol. These findings suggested that the preprandial rise in plasma ghrelin that is seen in sheep on programmed feeding does not influence VFI but is likely to be important in the postprandial rise in GH levels. Thus, ghrelin does not appear to be a significant regulator of ingestive behavior in this species of ruminant but acts centrally to indirectly regulate GH and LH secretion.

  5. Plasma insulin, leptin, adiponectin, resistin, ghrelin, and melatonin in nonalcoholic steatohepatitis patients treated with melatonin.

    Science.gov (United States)

    Gonciarz, Maciej; Bielański, Wladyslaw; Partyka, Robert; Brzozowski, Tomasz; Konturek, Piotr C; Eszyk, Jerzy; Celiński, Krzysztof; Reiter, Russel J; Konturek, Stanislaw J

    2013-03-01

    Insulin resistance, oxidative stress, and an abnormal production of adipokines and cytokines are implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH). Recently, we reported a significant improvement in plasma liver enzymes among patients with NASH treated with melatonin. In this study, we investigated the effect of melatonin, administered at a dose of 10 mg/day for 28 days to 16 patients with histologically proven NASH on insulin resistance (HOMA-IR), on the plasma levels of adiponectin, leptin, ghrelin, and resistin. Additionally, plasma levels of aminotransferases and gamma glutamyltranspeptidase as well as plasma concentrations of melatonin were evaluated. Median baseline values of HOMA-IR, leptin (ng/mL), and resistin (pg/mL) in patients with NASH were significantly higher in comparison with controls: 4.90 versus 1.60, 10.70 versus 4.30, and 152 versus 91, respectively. Median adiponectin level (μg/mL) was decreased in patients compared to controls: 6.40 versus 16.25; no significant difference in ghrelin levels between patients and controls was found. After melatonin treatment, the median value of HOMA-IR was significantly reduced by 60% as compared to baseline values, whereas adiponectin, leptin, and ghrelin plasma levels rose significantly by 119%, 33%, and 20%, respectively; the difference between pre-/posttreatment in plasma resistin levels was not significant. These findings make melatonin a suitable candidate for testing in patients with NASH in the large controlled clinical trials.

  6. Enhanced plasma ghrelin levels in Helicobacter pylori-colonized,interleukin-1-receptor type 1-homozygous knockout (IL-1R1-/-) mice

    Institute of Scientific and Technical Information of China (English)

    Yuka Abiko; Hidekazu Suzuki; Tatsuhiro Masaoka; Sachiko Nomura; Kumiko Kurabayashi; Hiroshi Hosoda; Kenji Kangawa; Toshifumi Hibi

    2005-01-01

    AIM: Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor, and it plays a role in stimulating the growth hormone secretion, food intake,body weight gain and gastric motility. Eradication of Helicobacter pylori(H pylori) was shown to be associated with increase of the body weight. On the other hand, H pylori infection evokes the release of gastric IL-1β. The present study was designed to investigate the involvement of the gastric IL-1 signal in the ghrelin dynamics in H pyloricolonized mice.METHODS: Twelve-week-old female IL-1-receptor type 1-homozygous-knockout mice (IL-1R1-/-) and their wild-type littermates (WT) were orally inoculated with H pylori (Hp group), while other cohorts received oral inoculation of culture medium (Cont group). Thirteen weeks after the inoculation, the mice were examined. The plasma and stomach ghrelin levels and the gastric preproghrelin mRNA were measured.RESULTS: Although the WT mice with H pylori infection showed a significantly decreased body weight as compared with that of the animals without H pylori infection,H pylori infection did not influence the body weight of the IL-1R1-knockout (IL-1R1-/-) mice. In the H pylori-infected IL-1R1-/-mice, the total and active ghrelin levels in the plasma were significantly increased, and the gastric ghrelin level was decreased. No significant differences were noted in the gastric preproghrelin mRNA expression.CONCLUSION: Ghrelin secretion triggered by H pylori infection might be suppressed by IL-1β, the release of which is also induced by the infection, resulting in the body weight loss of mice with H pylori infection.

  7. Ghrelin levels in chronic periodontitis patients.

    Science.gov (United States)

    Yılmaz, Gülin; Kırzıoğlu, Fatma Yeşim; Doğuç, Duygu Kumbul; Koçak, Havva; Orhan, Hikmet

    2014-01-01

    Ghrelin is a peptide hormone that has modulatory effects on the immune system. This study was designed to evaluate plasma ghrelin levels in patients with chronic periodontitis and to investigate if a relationship exists between ghrelin and periodontal parameters, serum cytokines, and bone turnover markers. Thirty-five chronic periodontitis patients (CP) and periodontal healthy individuals (C) were included in this study. Periodontal parameters were recorded. Blood samples were obtained to determine the levels of total and acylated ghrelin, interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), the soluble receptor activator nuclear factor kappaB ligand (sRANKL), alkaline phosphatase (ALP), and osteocalcin (OSC). Plasma levels of total and acylated ghrelin were significantly elevated in the CP group compared with the C group (p periodontal parameters. Our results indicate an increase of total and acylated ghrelin levels in patients with chronic periodontitis. Further, studies in larger populations (which could include ghrelin levels in gingival tissue, gingival crevicular fluid, and saliva) are needed in order to confirm the role of ghrelin in periodontal disease.

  8. Increased ghrelin but low ghrelin-reactive immunoglobulins in a rat model of methotrexate chemotherapy-induced anorexia

    Directory of Open Access Journals (Sweden)

    Marie François

    2016-07-01

    Full Text Available Background and aims: Cancer chemotherapy is commonly accompanied by mucositis, anorexia, weight loss and anxiety independently from cancer-induced anorexia-cachexia, further aggravating clinical outcome. Ghrelin is a peptide hormone produced in gastric mucosa that reaches the brain to stimulate appetite. In plasma, ghrelin is protected from degradation by ghrelin-reactive immunoglobulins (Ig. To analyze possible involvement of ghrelin in the chemotherapy-induced anorexia and anxiety, gastric ghrelin expression, plasma levels of ghrelin and ghrelin-reactive IgG were studied in rats treated with methotrexate (MTX.Methods: Rats received MTX (2.5 mg/kg, S.C. for three consecutive days and were killed 3 days later, at the peak of anorexia and weight loss. Control rats received phosphate-buffered saline. Preproghrelin mRNA expression in the stomach was analyzed by in situ hybridization. Plasma levels of ghrelin and ghrelin-reactive IgG were measured by immunoenzymatic assays and IgG affinity kinetics by surface plasmon resonance. Anxiety- and depression-like behaviors in MTX-treated anorectic and in control rats were evaluated in the elevated plus-maze and the forced-swim test, respectively.Results: In MTX-treated anorectic rats the number of preproghrelin mRNA-producing cells was found increased (by 51.3%, p<0.001 as well were plasma concentrations of both ghrelin and des-acyl-ghrelin (by 70.4%, p<0.05 and 98.3%, p<0.01, respectively. In contrast, plasma levels of total IgG reactive with ghrelin and des-acyl-ghrelin were drastically decreased (by 87.2% and 88.4%, respectively, both p<0.001, and affinity kinetics of these IgG were characterized by increased small and big Kd, respectively. MTX-treated rats displayed increased anxiety- but not depression-like behavior.Conclusion: MTX-induced anorexia, weight loss and anxiety are accompanied by increased ghrelin production and by a decrease of ghrelin-reactive IgG levels and affinity binding properties

  9. Effects of intravenous ghrelin injection on plasma growth hormone, insulin and glucose concentrations in calves at weaning.

    Science.gov (United States)

    Fukumori, Rika; Mita, Takako; Sugino, Toshihisa; Hasegawa, Yoshihisa; Kojima, Masayasu; Kangawa, Kenji; Obitsu, Taketo; Taniguchi, Kohzo

    2013-04-01

    Ghrelin action, which stimulates growth hormone (GH) secretion, may alter during the weaning period in calves. Our objective was to compare the effects of intravenous ghrelin injection on plasma GH, insulin and glucose concentrations in calves around the weaning period. Four Holstein bull calves were fed whole milk and allowed free access to solid feeds, and weaned at 7 weeks of age. Measurements were performed at weeks 1, 2, 4, 6, 7, 9, 11 and 13, when calves were intravenously injected with ghrelin (1.0 μg/kg body weight (BW)) through a catheter, and jugular blood samples were obtained temporally relative to the injection time. Estimated digestible energy intake per metabolic BW transiently decreased at week 7 because of low solid intake immediately after weaning, and thereafter gradually increased. Plasma insulin and glucose concentrations were not affected by ghrelin injection at all ages. In contrast, plasma GH concentrations increased with ghrelin injection at all ages. The incremental area of GH at week 7 was greatest and significantly higher compared with weeks 2, 4, 6 and 9. This result suggests that nutrient insufficiency immediately after weaning enhances GH responsiveness to ghrelin.

  10. Role of the duodenum in regulation of plasma ghrelin levels and body mass index after subtotal gastrectomy

    Institute of Scientific and Technical Information of China (English)

    Hai-Tao Wang; Qi-Cheng Lu; Qing Wang; Rong-Chao Wang; Yun Zhang; Hai-Long Chen; Hong Zhao; Hai-Xin Qian

    2008-01-01

    AIM: To investigate the role of the duodenum in the regulation of plasma ghrelin levels and body mass index (BMI), and the correlation between them after subtotal gastrectomy.METHODS: Forty-two patients with To-1No-1M0 gastric cancer were divided into two groups after gastrectomy according to digestive reconstruction pattern,Billroth I group (n = 23) and Billroth Ⅱ group (n = 19).Ghrelin levels were determined with radioimmunoassay (RIA) before and on d 1, 7, 30 and 360 after gastrectomy,and BMI was also measured.RESULTS: The two groups had identical postoperative trends in ghrelin alterations during the early stage, both decreasing sharply to a nadir on d 1 (36.7% vs 35.7%),then markedly increasing on d 7 (51.0% vs 51.1%). On d 30, ghrelin levels in the Billroth I group were slightly higher than those in the Billroth Ⅱ group. However,those of the Billroth I group recovered to 93.6% on d 360, which approached, although lower than, the preoperative levels, and no statistically significant difference was observed. Those of the Billroth Ⅱ group recovered to only 81.6% and manifested significant discrepancy with preoperative levels (P = 0.033).Compared with preoperative levels, ghrelin levels of the two groups decreased by 6.9% and 18.4% and BMI fell by 3.3% and 6.4%, respectively. The linear regression correlations were revealed in both groups between decrease of ghrelin level and BMI (R12 = 0.297, P = 0.007;R22 = 0.559, P < 0.001).CONCLUSION: Anatomically and physiologically, the duodenum compensatively promotes ghrelin recovery and accordingly enhances BMI after gastrectomy.Regarding patients with insufficient ghrelin secretion,ghrelin is positively associated with BMI.

  11. [Relationship of plasma ghrelin, IGF-1 and insulin with the growth and development of 2 -7 year-old children with small for gestational age at birth].

    Science.gov (United States)

    Cheng, Yaying; Song, Guangyao; Zhou, Lixia; Cai, Baoping; Zhao, Xiumian; Yin, Jianying

    2012-01-01

    To explore the relationship of Ghrelin, insulin-like growth factor-1 (IGF-1) and insulin with the growth and development of 2 -7 year-old children with small for gestational age (SGA) at birth. The levels of ghrelin, IGF-1, IGFBP-3, insulin and glucose were measured in the children with preterm SGA and term SGA and compared with the children with preterm appropriate for gestational age (AGA) and term AGA. The correlation of ghrelin with IGF-1, IGFBP-3 and insulin was analyzed. Plasma ghrelin in preterm SGA was higher than that in term SGA (P 0.05). Plasma ghrelin in preterm AGA and term SGA was higher than that in term AGA (P development of preterm and SGA children, regardless of the magnitude of their catch up growth. As a re-regulatory factor to insulin, ghrelin regulates the energy metabolism in a form of negative feedback.

  12. The Effect of Glycemic Control on Plasma Ghrelin and Serum IGF-1 Levels in Type 1 Diabetic Girls

    Directory of Open Access Journals (Sweden)

    Tolga Altuğ Şen

    2009-12-01

    Full Text Available Introduction: The aim of this study was to investigate the effect of glycemic control on plasma ghrelin levels and serum IGF-1 levels in girls with type 1 diabetes. Materials and Method: The study group composed of 32 diabetic girls between the ages of 14.0-20.0 years with Tanner pubertal stage 5; and 15 healthy girls in similar ages with Tanner pubertal stage 5 formed the control group. Diabetic girls were classified as well glycemic controlled (n=18 and poor glycemic controlled (n=14 according to last year’s mean glycosylated hemoglobin levels. All subjects were tested for fasting plasma ghrelin and serum IGF-1 levels. Results: The mean fasting plasma ghrelin levels in girls with well controlled diabetes, in girls wtih poor controlled diabetes and in control group were 483.4±221.9 pg/ml, 310.7±110.2 pg/ml, 471.9±175.0 pg/ml respectively. The mean serum IGF-1 levels in girls with well controlled diabetes was 233.9±59.2 ng/ml, in girls with poor controlled diabetes 183.9±36.7 ng/ml, and in healthy controls 247.3±48.5 ng/ml. Plasma ghrelin levels and serum IGF-1 levels were similar in girls with well controlled diabetes and in the control group, however it was significantly supressed in those with poorly controlled diabetes. Conclusion: The metabolic control may be a determinative factor on plasma ghrelin and serum IGF-1 levels of type 1 diabetics. Plasma ghrelin and serum IGF-1 levels were similar in well glycemic controlled diabetics and control group, while they were suppressed in only poor glycemic controlled diabetics. (Journal of Current Pediatrics 2009; 7: 104-10

  13. Effects of plasma ghrelin, obestatin, and ghrelin/obestatin ratio on blood pressure circadian rhythms in patients with obstructive sleep apnea syndrome

    Institute of Scientific and Technical Information of China (English)

    Liu Weiying; Yue Hongmei; Zhang Jiabin; Pu Jiayuan; Yu Qin

    2014-01-01

    Background Obstructive sleep apnea syndrome (OSAS) is strongly associated with obesity and with cardiovascular disease.Ghrelin and obestatin are two peptides from the same source but have opposite roles.Both of them can affect feeding and regulate vascular tune.The aim of this study was to investigate the relationship between plasma ghrelin,obestatin,the ratio of ghrelin and obestatin (G/O) and sleep parameters and blood pressure circadian rhythms in patients with OSAS.Methods This study enrolled 95 newly diagnosed over-weight OSAS patients (OSAS group),30 body mass index (BMI)-match non-OSAS adults (over-weight group) and 30 non-OSAS normal weight adults (control group).Polysomnography (PSG) was performed in the OSAS group and over-weight group.Blood pressure of all subjects was monitored by means of 24-hour ambulatory blood pressure monitoring.The concentration of plasma ghrelin and obestatin was detected by enzyme-linked immunosorbent assay (ELISA).Results Plasma ghrelin levels in the OSAS group and over-weight group were significantly lower than that of the control group (P <0.05).Plasma obestatin levels were lower in the over-weight group and OSAS group,but there was no significant difference among the three groups.The blood pressure in OSAS patients was higher,and there was a significant difference in all blood pressure parameters compared to the control group,and in the daytime average diastolic blood pressure (DBP),nocturnal average systolic blood pressure (SBP) and DBP,DBP variability values as compared to over-weight subjects.Furthermore,there were significantly more non-dipper patterns of blood pressure (including hypertension and normotension) in the OSAS group than in the other two groups (P <0.01).Correlation analysis showed that ghrelin levels had a significant correlation with BMI and nocturnal average DBP but not with PSG parameters.In contrast,the G/O ratio had a negative correlation with apnea-hypopnea index (AHI) (P <0.05),as well as a

  14. Dietary unsaturated fatty acids increase plasma glucagon-like peptide-1 and cholecystokinin and may decrease premeal ghrelin in lactating dairy cows.

    Science.gov (United States)

    Bradford, B J; Harvatine, K J; Allen, M S

    2008-04-01

    Previous reports have indicated that dietary unsaturated fat can decrease energy intake of lactating dairy cattle. However, the mechanism for this response is unclear. To evaluate the potential role of gut peptides, periprandial concentrations of cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and ghrelin were measured. From a replicated 4 x 4 Latin square experiment, 4 cows from a single square were selected for analysis of responses to 3 treatments: a control diet (5.5% total fatty acids, 65% unsaturated), a diet with added saturated fat (SAT, 8.3% fatty acids, 47% unsaturated), and a diet with added unsaturated fat (UNS, 7.8% fatty acids, 63% unsaturated). The SAT treatment increased duodenal flow of saturated fatty acids compared with UNS and control and, despite the fact that ruminal biohydrogenation altered fatty acid profiles of digesta, UNS increased duodenal flow of unsaturated fatty acids compared with SAT and control. Blood samples were collected at 8-min intervals through the first 2 meals of the day and analyzed by commercial radioimmunoassays. The UNS treatment increased plasma CCK concentration relative to SAT and control, and increased plasma GLP-1 concentration compared with control. Furthermore, fat treatments tended to suppress the prandial ghrelin surge that was evident for control. Suppression of feed intake by unsaturated fats is likely mediated in part by increased secretion of CCK and GLP-1, and dietary fat may also inhibit ghrelin release before conditioned meals.

  15. Abnormal ghrelin secretion contributes to gastrointestinal symptoms in multiple system atrophy patients.

    Science.gov (United States)

    Ozawa, Tetsutaro; Tokunaga, Jun; Arakawa, Musashi; Ishikawa, Atsushi; Takeuchi, Ryoko; Mezaki, Naomi; Miura, Takeshi; Sakai, Naoko; Hokari, Mariko; Takeshima, Akari; Utsumi, Kota; Kondo, Takashi; Yokoseki, Akio; Nishizawa, Masatoyo

    2013-08-01

    Patients with multiple system atrophy (MSA) often have evidence of compromised gastrointestinal motility. Ghrelin is a gut hormone that influences gastrointestinal motility in humans. The aim of this study was to determine whether ghrelin secretion is affected in MSA patients, and to investigate the relation between ghrelin secretion and gastrointestinal symptoms. Plasma levels of active ghrelin and unacylated ghrelin were measured in patients with MSA (n = 30), other atypical parkinsonian disorders including progressive supranuclear palsy-Richardson syndrome and corticobasal syndrome (n = 24), and control subjects (n = 24) using enzyme-linked immunosorbent assays. Gastrointestinal symptoms were quantified in all subjects using a self-report questionnaire. The ratio of active ghrelin to total ghrelin in the plasma (active ghrelin ratio) was lower in patients with MSA (mean: 8.0 %) than in patients with other atypical parkinsonian disorders (mean: 13.7 %, P = 0.001) and control subjects (mean: 13.9 %, P = 0.001). The active ghrelin ratio was correlated with the severity of gastrointestinal symptoms in MSA (r = -0.5, P = 0.004). Our observations indicate that ghrelin secretion is affected in patients with MSA. The low active ghrelin ratio may contribute to gastrointestinal symptoms in MSA.

  16. Ghrelin; The Renown Hormone

    Directory of Open Access Journals (Sweden)

    H. Murat Bilgin

    2006-01-01

    Full Text Available Ghrelin , a 28 amino acid gastric peptide, was found to be a potent releaser of GH and in addition, actively participate in controlling energy balance and the regulation of food intake. Specifically, plasma ghrelin originates in the oxyntic gland where A-like cells exist and is secreted into the bloodstream. Lower concentrations have also been reported at various regions in the body. It is well known that ghrelin participates in the regulation of many functions in the body.

  17. Hypothalamic galanin and plasma leptin and ghrelin in the maintenance of energy intake in the Brattleboro rat.

    Science.gov (United States)

    Beck, Bernard; Max, Jean-Pierre

    2007-12-07

    Galanin, ghrelin, and leptin are three peptides involved in feeding regulation and more particularly in fat intake. The Brattleboro (di/di) rat is a genetic model of diabetes insipidus characterized by a preference for fat when it is in a food choice situation. Here, we measured hypothalamic galanin concentrations, plasma ghrelin and leptin and dietary preferences of adult di/di Brattleboro rats, di/+ and Long-Evans controls. The Brattleboro rats weighed significantly less than the di/+ rats (-18%; Pdiet and a high-carbohydrate diet. Galanin concentrations were significantly lower in di/di rats than in di/+ rats in the paraventricular nucleus (-56%; P<0.001), but not in the arcuate nucleus. Plasma leptin was significantly lower in the di/di rats than in the di/+ rats (3.49+/-0.20 vs. 6.94+/-0.49 ng/ml; P<0.001). Plasma ghrelin concentrations were significantly lower in Long-Evans rats than in the di/di rats (-21%; P< 0.01). Given that galanin mRNA is overexpressed in the paraventricular nucleus of Brattleboro rats, these data are consistent with increased release of the peptide. In the Brattleboro rat, this overactive galanin system and the variations of ghrelin and leptin maintain an orexigenic drive favoring a preferential intake of fat which provides the animal with enough energy for its metabolism.

  18. Ghrelin reverses experimental diabetic neuropathy in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kyoraku, Itaru; Shiomi, Kazutaka [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan); Kangawa, Kenji [Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka 565-8565 (Japan); Nakazato, Masamitsu, E-mail: nakazato@med.miyazaki-u.ac.jp [Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan)

    2009-11-20

    Ghrelin, an acylated peptide produced in the stomach, increases food intake and growth hormone secretion, suppresses inflammation and oxidative stress, and promotes cell survival and proliferation. We investigated the pharmacological potential of ghrelin in the treatment of polyneuropathy in uncontrolled streptozotocin (STZ)-induced diabetes in mice. Ghrelin or desacyl-ghrelin was administered daily for 4 weeks after STZ-induced diabetic polyneuropathy had developed. Ghrelin administration did not alter food intake, body weight gain, blood glucose levels, or plasma insulin levels when compared with mice given saline or desacyl-ghrelin administration. Ghrelin administration ameliorated reductions in motor and sensory nerve conduction velocities in diabetic mice and normalized their temperature sensation and plasma concentrations of 8-isoprostaglandin {alpha}, an oxidative stress marker. Desacyl-ghrelin failed to have any effect. Ghrelin administration in a mouse model of diabetes ameliorated polyneuropathy. Thus, ghrelin's effects represent a novel therapeutic paradigm for the treatment of this otherwise intractable disorder.

  19. Effects of calcium salts of long-chain fatty acids and rumen-protected methionine on plasma concentrations of ghrelin, glucagon-like peptide-1 (7 to 36) amide and pancreatic hormones in lactating cows.

    Science.gov (United States)

    Fukumori, R; Sugino, T; Shingu, H; Moriya, N; Hasegawa, Y; Kojima, M; Kangawa, K; Obitsu, T; Kushibiki, S; Taniguchi, K

    2012-02-01

    Our objective was to determine the effects of calcium salts of long-chain fatty acids (CLFAs) and rumen-protected methionine (RPM) on plasma concentrations of ghrelin, glucagon-like peptide-1 (7 to 36) amide, and pancreatic hormones in lactating cows. Four Holstein cows in midlactation were used in a 4 by 4 Latin square experiment in each 2-wk period. Cows were fed corn silage-based diets with supplements of CLFAs (1.5% added on dry matter basis), RPM (20 g/d), CLFAs plus RPM, and without supplement. Jugular blood samples were taken from 1 h before to 2 h after morning feeding at 10-min intervals on day 12 of each period. CLFAs decreased dry matter intake, but RPM did not affect dry matter intake. Both supplements of CLFAs and RPM did not affect metabolizable energy intake and milk yield and composition. Plasma concentrations of NEFAs, triglyceride (TG), and total cholesterol (T-Cho) were increased with CLFAs alone, but increases of plasma concentrations of TG and T-Cho were moderated by CLFAs plus RPM. Calcium salts of long-chain fatty acids increased plasma ghrelin concentration, and the ghrelin concentration with CLFAs plus RPM was the highest among the treatments. Plasma concentrations of glucagon-like peptide-1, glucagon, and insulin were decreased with CLFAs, whereas adding RPM moderated the decrease of plasma glucagon concentration by CLFAs. These results indicate that the addition of methionine to cows given CLFAs increases plasma concentrations of ghrelin and glucagon associated with the decrease in plasma concentrations of TG and T-Cho.

  20. Reconstruction-Dependent Recovery from Anorexia and Time-Related Recovery of Regulatory Ghrelin System in Gastrectomized Rats

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    Masaru Koizumi

    2010-01-01

    Full Text Available Gastrectomy reduces food intake and body weight (BW hampering recovery of physical conditions. It also reduces plasma levels of stomach-derived orexigenic ghrelin. This study explored changes in orexigenic ghrelin system in rats receiving total gastrectomy with Billroth II (B-II or Roux-en-Y (R-Y method. Feeding and BW were reduced by gastrectomy and subsequently recovered to a greater extent with R-Y than B-II while plasma ghrelin decreased similarly. At postoperative 12th week, ghrelin contents increased in the duodenum and pancreas, plasma ghrelin levels increased upon fasting, and ghrelin injection promoted feeding but not in earlier periods. In summary, gastrectomized rats partially recover feeding and BW, in a reconstruction-dependent manner. At 12th week, ghrelin is upregulated in extra-stomach tissues, plasma ghrelin levels are physiologically regulated, and orexigenic effect of exogenous ghrelin is restored. This time-related recovery of ghrelin system may provide a strategy for promoting feeding, BW, and thereby physical conditions in gastrectomized patients.

  1. Ghrelin and Functional Dyspepsia

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    Takashi Akamizu

    2010-01-01

    Full Text Available The majority of patients with dyspepsia have no identifiable cause of their disease, leading to a diagnosis of functional dyspepsia (FD. While a number of different factors affect gut activity, components of the nervous and endocrine systems are essential for normal gut function. Communication between the brain and gut occurs via direct neural connections or endocrine signaling events. Ghrelin, a peptide produced by the stomach, affects gastric motility/emptying and secretion, suggesting it may play a pathophysiological role in FD. It is also possible that the functional abnormalities in FD may affect ghrelin production in the stomach. Plasma ghrelin levels are reported to be altered in FD, correlating with FD symptom score. Furthermore, some patients with FD suffer from anorexia with body-weight loss. As ghrelin increases gastric emptying and promotes feeding, ghrelin therapy may be a new approach to the treatment of FD.

  2. Fish oil and olive oil can modify insulin resistance and plasma desacyl-ghrelin in rats

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    Atoosa Saidpour

    2011-01-01

    Full Text Available Background: Evidence exists for reciprocal effects of insulin and desacyl-ghrelin (DAG concentration, but the association between different fatty acid saturation in high fat diet (HFD and these hormones remain to be established. To evaluate the impact of different sources of dietary fat and the level of fatty acid saturation on plasma insulin and DAG levels and also the association of DAG with insulin action this study was carried out. Methods: Male weaning Wistar rats were randomly divided into four groups of HFDs, high fat butter (HF-B, high fat soy (HF-S, high fat olive (HF-O, high fat fish (HF-F, and a group of standard diet (SD. Blood samples were collected after 8 weeks and after they were fasted for 24 h. Body weight, food intake, plasma glucose, insulin, DAG and insulin resistance (HOMA-IR were measured. Results: Plasma insulin levels at fed and fasted status, were significantly higher in rats on HF-B compared to those on SD, HF-F and HF-O diets (P<0.05. Insulin concentration in rats on HF-S was also higher than those on SD, HF-F and HF-O diets (P<0.05, in the feeding status. Insulin resistance was significantly higher in rats on HF-B, compared to those on SD, HF-F and HF-O (P<0.05. Rats that were fed with HF-B diet had lower fasting plasma DAG levels than the SD, HF-F and HF-O groups (P<0.05; furthermore, the HF-F group had significantly higher DAG level than the HF-S groups (P<0.05. Conclusions: Fish and olive oils may hence contribute to lower insulin level and HOMA-IR by increasing DAG concentration and may have more health benefits than other fat sources in diets.

  3. Growth Hormone, Insulin Resistance Index, Lipid Profile, and Cardiorespiratory Function in Obese and Lean Inactive Young Men: Correlations with Plasma Acylated Ghrelin Levels

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    Hasan Matinhomaee

    2011-01-01

    Full Text Available Introduction: Plasma ghrelin is influenced by nutritional status and is thought to play a role in acute and chronic regulating of food intake and body weight. The purpose of this study was to compare GH, insulin resistance index, lipid profile, and cardiorespiratory function in obese and lean inactive young men and determine their relationships with plasma acylated ghrelin levels. Methods: Study design of this research was causal-comparative. Obese (n=19, BMI: 31.0 kg/m2 and lean (n=19, BMI: 18.5 kg/m2 young men, without experience of regular physical activity during the previous six months, were selected. After 12 h fasting (at 8 a.m., blood samples were collected to determine blood parameter levels. Also, maximal oxygen uptake (as indicator of cardiorespiratory function of subjects was assessed. Results: Insulin levels and HOMA-IR (insulin resistance index were higher, and GH, acylated ghrelin and maximal oxygen uptake levels were lower in obese men compared to lean men (P0.01. Plasma acylated ghrelin concentrations were negatively correlated to body mass, body fat percent, body mass index, insulin and HOMA-IR, and positively correlated to GH levels and maximal oxygen uptake (P0.01.Conclusion: Obese and lean inactive young men had different levels of acylated ghrelin, GH, insulin, insulin resistance index, cardiorespiratory function and body fat percent. Body fat percent, insulin, and GH levels appear to be the strongest determinant factors of acylated ghrelin levels.

  4. The intestinal lymph fistula model--a novel approach to study ghrelin secretion.

    Science.gov (United States)

    Tong, Jenny; Tschöp, Matthias H; Aulinger, Benedikt A; Davis, Harold W; Yang, Qing; Liu, Jianhua; Gaylinn, Bruce D; Thorner, Michael O; D'Alessio, David; Tso, Patrick

    2010-03-01

    The orexigenic hormone ghrelin is secreted from the stomach and has been implicated in the regulation of energy and glucose homeostasis. We hypothesized that ghrelin, like other gastrointestinal (GI) hormones, is present in intestinal lymph, and sampling this compartment would provide advantages for studying ghrelin secretion in rodents. Blood and lymph were sampled from catheters in the jugular vein and mesenteric lymph duct before and after intraduodenal (ID) administration of isocaloric Ensure, dextrin, or Liposyn meals or an equal volume of saline in conscious Sprague-Dawley rats. Total ghrelin levels were measured using an established radioimmunoassay. Acyl and des-acyl ghrelin were measured using two-site ELISA. Fasting ghrelin levels in lymph were significantly higher than in plasma (means +/- SE: 3,307.9 +/- 272.9 vs. 2,127.1 +/- 115.0 pg/ml, P = 0.004). Postingestive acyl and des-acyl ghrelin levels were also significantly higher, whereas the ratio of acyl:des-acyl ghrelin was similar in lymph and plasma (0.91 +/- 0.28 vs. 1.20 +/- 0.36, P = 0.76). The principle enzymes responsible for deacylation of ghrelin were lower in lymph than in plasma. Following ID Ensure, maximum ghrelin suppression occurred at 2 h in lymph compared with at 1 h in plasma. The return of suppressed ghrelin levels to baseline was also delayed in lymph. Similarly, dextrin also induced significant suppression of ghrelin (two-way ANOVA: P = 0.02), whereas Liposyn did not (P = 0.32). On the basis of these findings, it appears that intestinal lymph, which includes drainage from the interstitium of the GI mucosa, is enriched in ghrelin. Despite reduced deacylating activity in lymph, there is not a disproportionate amount of acyl ghrelin in this pool. The postprandial dynamics of ghrelin are slower in lymph than plasma, but the magnitude of change is greater. Assessing ghrelin levels in the lymph may be advantageous for studying its secretion and concentrations in the gastric mucosa.

  5. Effect of preduodenal lipase inhibition in suckling rats on dietary octanoic acid (C8:0) gastric absorption and plasma octanoylated ghrelin concentration.

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    Lemarié, F; Cavalier, J-F; Garcia, C; Boissel, F; Point, V; Catheline, D; Legrand, P; Carrière, F; Rioux, V

    2016-09-01

    Part of medium chain fatty acids (MCFAs) coming from dietary triglycerides (TGs) can be directly absorbed through the gastric mucosa after the action of preduodenal lipase (lingual lipase in the rat). MCFA gastric absorption, particularly that of octanoic acid (C8:0), may have a physiological importance in the octanoylation of ghrelin, the orexigenic gastric peptide acting as an endogenous ligand of the hypothalamic growth hormone secretagogue receptor 1a (GHSR-1a). However, the amount of C8:0 absorbed in the stomach and its metabolic fate still haven't been clearly characterized. The purpose of the present study was to further characterize and quantify the importance of preduodenal lipase activity on the release and gastric absorption of dietary C8:0 and on the subsequent ghrelin octanoylation in the stomach mucosa. Fifteen days old rats received fat emulsions containing triolein or [1,1,1-(13)C]-Tri-C8:0 and a specific inhibitor of preduodenal lipase, 5-(2-(benzyloxy)ethoxy)-3-(3-phenoxyphenyl)-1,3,4-oxadiazol-2(3H)-one or BemPPOX. The fate of the (13)C-C8:0 was followed in rat tissues after 30 and 120min of digestion and octanoylated ghrelin was measured in the plasma. This work (1) demonstrates that part of C8:0 coming from Tri-C8:0 is directly absorbed at the gastric level, (2) allows the estimation of C8:0 gastric absorption level (1.3% of the (13)C-C8:0 in sn-3 position after 30min of digestion), as well as (3) the contribution of rat lingual lipase to total lipolysis and to duodenal absorption of dietary FAs (at least 30%), (4) shows no short-term effect of dietary Tri-C8:0 consumption and subsequent increase of C8:0 gastric tissue content on plasma octanoylated ghrelin concentration.

  6. The Effect of an Eight-Week Period of Aerobic Exercise on Plasma Concentration of Ghrelin and Growth Hormone in Young Women

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    Rashidlamir

    2011-12-01

    Full Text Available Introduction: Ghrelin is a peptide which is secreted from human stomach. It has an important role in the secretion of growth hormone, energy balance, obesity, food intake behavior, and some cardiovascular functions. The purpose of this study was to assess the effects of an eight-week of aerobic exercise on plasma concentration of ghrelin and GH in non-athletic young women. Methods: Twenty young non-athletic women with mean age of 22±2/1 years and mean BMI of 21±1/07 Kg/m2 voluntarily entered the study and they were randomly divided into control and experimental groups. Experimental group conducted an aerobic exercise program three sessions each week and 60 minutes in each session with 70-80% of maximum heart rate for 8 weeks. Control group didn’t exercise. Blood samples were taken 48 hours before the first and after the last session of exercise. Plasma concentrations of ghrelin and growth hormone were measured by ELISA and radioimmunoassay methods, respectively. Data was analyzed by independent samples T test and Pearson correlation test by SPSS(version16. Results: The eight-week period of aerobic exercise caused a significant increase in plasma concentration of ghrelin and a significant decrease in plasma concentration of GH. Conclusion: It can be concluded from the study that exercise-induced increase in plasma ghrelin in response to negative energy balance didn’t stimulate GH secretion, so other mechanisms may be effective in this regard.

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

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    Gómez-Díaz, Rita Angélica; Gómez-Medina, Monica P.; Ramírez-Soriano, Eleazar; López-Robles, Lucio; Aguilar-Salinas, Carlos A.; Saucedo, Renata; Zarate, Arturo; Valladares-Salgado, Adan; Wacher, Niels H.

    2016-01-01

    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. PMID:27476441

  8. Aging effects on exercise-induced alternations in plasma acylated ghrelin and leptin in male rats.

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    Hsu, Ya-Wen; Pan, Yi-Ju; Cho, Yu-Min; Liou, Tsan-Hon; Chou, Pesus; Wang, Paulus S

    2011-05-01

    Ghrelin and exercise have been known to stimulate the release of growth hormone which is related to the glucose metabolism. However, the age effects of exercise on ghrelin in energy consumption remain unclear. Young (3 month old) and middle-aged (12 month old) Sprague-Dawley male rats were overnight fasted, and then randomly partitioned into exercise and control groups. Exercise groups swam for 20 min in 25°C water. Rats immersed in 25°C water for 20 min were used as control animals. All blood samples were collected before and 10, 20, 30, and 60 min after initiation of exercise via the right jugular vein. Our results indicated that the swimming regimen decreased the secretion of acylated ghrelin and insulin, but increased the secretion of leptin, lactate, and glucose. In addition, exercise significantly amplified the inverse correlation between leptin and acylated ghrelin (r ghrelin. A 20-min exercise regimen decreased acylated ghrelin and increased leptin with inverse correlation between them which was strengthened during exercise, but were not influenced by age.

  9. Dietary Caprylic Acid (C8:0) Does Not Increase Plasma Acylated Ghrelin but Decreases Plasma Unacylated Ghrelin in the Rat

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    Fanny Lemarié; Erwan Beauchamp; Stéphanie Dayot; Cécile Duby; Philippe Legrand; Vincent Rioux

    2015-01-01

    International audience; Focusing on the caprylic acid (C8:0), this study aimed at investigating the discrepancy between the formerly described beneficial effects of dietary medium chain fatty acids on body weight loss and the C8:0 newly reported effect on food intake via ghrelin octanoylation. During 6 weeks, Sprague-Dawley male rats were fed with three dietary C8:0 levels (0, 8 and 21% of fatty acids) in three experimental conditions (moderate fat, caloric restriction and high fat). A specif...

  10. Ghrelin Cells in the Gastrointestinal Tract

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    Ichiro Sakata

    2010-01-01

    Full Text Available Ghrelin is 28-amino-acid peptide that was discovered from the rat and human stomach in 1999. Since the discovery of ghrelin, various functions of ghrelin, including growth hormone release, feeding behavior, glucose metabolism, memory, and also antidepressant effects, have been studied. It has also been reported that ghrelin in the gastrointestinal tract has an important physiological effect on gastric acid secretion and gastrointestinal motility. Ghrelin has a unique structure that is modified by O-acylation with n-octanoic acid at third serine residues, and this modification enzyme has recently been identified and named ghrelin O-acyl transferase (GOAT. Ghrelin is considered to be a gut-brain peptide and is abundantly produced from endocrine cells in the gastrointestinal mucosa. In the gastrointestinal tract, ghrelin cells are most abundant in the stomach and are localized in gastric mucosal layers. Ghrelin cells are also widely distributed throughout the gastrointestinal tract. In addition, abundance of ghrelin cells in the gastric mucosa is evolutionally conserved from mammals to lower vertebrates, indicating that gastric ghrelin plays important roles for fundamental physiological functions. Ghrelin cells in the gastrointestinal tract are a major source of circulating plasma ghrelin, and thus understanding the physiology of these cells would reveal the biological significance of ghrelin.

  11. Appetite regulation is independent of the changes in ghrelin levels in pregnant rats fed low-protein diet.

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    Gao, Haijun; Tanchico, Daren T; Yallampalli, Uma; Balakrishnan, Meena P; Yallampalli, Chandra

    2015-04-01

    Gestational protein restriction causes hypertension in the adult offspring. Very little is known about the food intake regulation and ghrelin signaling in pregnant dams fed a low-protein (LP) diet. We hypothesized that diet intake and ghrelin signaling are altered in pregnant rats fed the low-protein diet. Sprague-Dawley rats were fed a control (CT) or LP diet from Day 3 of pregnancy. Diet intake and body weight were monitored daily. Expression of ghrelin production-related genes in the stomach and appetite-related genes in the hypothalamus was analyzed by real-time PCR. Plasma levels of total and active ghrelin, growth hormone and leptin were measured by ELISA. Main results include: (1) Daily diet intake was greater in the LP group than in the CT group in early pregnancy, but substantially lower in late pregnancy; (2) Daily gain in body weight was substantially lower in the LP group in late pregnancy; (3) Expression of ghrelin production-related genes in the stomach and plasma total ghrelin levels were increased in LP group in late pregnancy; (4) Plasma active ghrelin levels were elevated in the LP group at mid-late pregnancy, but growth hormone and leptin levels were uncorrelated with active ghrelin in late pregnancy; and (5) Hypothalamic expression of ghrelin-stimulated genes in LP rats was unassociated with the changes in both plasma ghrelin levels and the diet intake. Taken together, the appetite in LP rats is greater in early pregnancy but reduced at late pregnancy, possibly due to ghrelin insensitivity in appetite regulation. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  12. Presence of adropin, nesfatin-1, apelin-12, ghrelins and salusins peptides in the milk, cheese whey and plasma of dairy cows.

    Science.gov (United States)

    Aydin, Suleyman

    2013-05-01

    Biological fluids (milk and serum/plasma) and cheese whey milk-derived fluid contain numerous molecules, especially amino acids and proteins. Therefore, the purpose of this study was to find out whether cheese whey (n:6), cow milk (n:6) and its blood (n=6) have adropin, nesfatin-1, apelin-12, ghrelins and salusin peptides. Adropin, nesfatin-1, apelin-12 concentrations were measured by ELISA, whereas ghrelin and salusin concentrations were measured by EIA methods. It was found that adropin, nesfatin-1, apelin-12, des-acylated ghrelin and salusins in cheese whey were higher than in the corresponding milk peptides and plasma of dairy cows, with the exception of salusin alpha and acylated ghrelin in milk being the same than that of the corresponding cheese whey concentration and plasma of dairy cows. A correlation was also found between milk peptides and cheese whey, as also with plasma of dairy cows. The data suggest that peptides in cow milk might be an important and nutritious food for (neonatal) calves and human diet due to their biological and physiological properties.

  13. Calorie-restricted weight loss reverses high-fat diet-induced ghrelin resistance, which contributes to rebound weight gain in a ghrelin-dependent manner.

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    Briggs, Dana I; Lockie, Sarah H; Wu, Qunli; Lemus, Moyra B; Stark, Romana; Andrews, Zane B

    2013-02-01

    Twelve weeks of high-fat diet feeding causes ghrelin resistance in arcuate neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons. In the current study, we investigated whether diet-induced weight loss could restore NPY/AgRP neuronal responsiveness to ghrelin and whether ghrelin mediates rebound weight gain after calorie-restricted (CR) weight loss. Diet-induced obese (DIO) mice were allocated to one of two dietary interventions until they reached the weight of age-matched lean controls. DIO mice received chow diet ad libitum or chow diet with 40% CR. Chow-fed and high-fat-fed mice served as controls. Both dietary interventions normalized body weight, glucose tolerance, and plasma insulin. We show that diet-induced weight loss with CR increases total plasma ghrelin, restores ghrelin sensitivity, and increases hypothalamic NPY and AgRP mRNA expression. We propose that long-term DIO creates a higher body weight set-point and that weight loss induced by CR, as seen in the high-fat CR group, provokes the brain to protect the new higher set-point. This adaptation to weight loss likely contributes to rebound weight gain by increasing peripheral ghrelin concentrations and restoring the function of ghrelin-responsive neuronal populations in the hypothalamic arcuate nucleus. Indeed, we also show that DIO ghrelin-knockout mice exhibit reduced body weight regain after CR weight loss compared with ghrelin wild-type mice, suggesting ghrelin mediates rebound weight gain after CR weight loss.

  14. Changes in plasma levels of ghrelin, leptin, and other hormonal and metabolic parameters following standardized breakfast, lunch, and physical exercise before and after a multidisciplinary weight-reduction intervention in obese adolescents.

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    Rigamonti, A E; Agosti, F; De Col, A; Marazzi, N; Lafortuna, C L; Cella, S G; Muller, E E; Sartorio, A

    2010-10-01

    To investigate in severely obese adolescents the effects of a 3-week multidisciplinary weight-reduction intervention involving moderate energy restriction, individualised physical activity and behavior therapy on the response of some hormonal and metabolic parameters to meals and exercise. Clinical longitudinal study on inpatients in a specialised institution. A total of 20 obese adolescents (10 boys and 10 girls) aged 12-17 yr [body mass index (BMI): 37.7±6.1 kg/m2; fat mass (FM): 44.8±13.2 kg]. The changes in plasma concentration of leptin, ghrelin, GH, IGF-I, insulin, glucose, and non-esterified fatty acids (NEFA) in response to standardised meals and exercise bouts were measured before and after the weight-reduction intervention. At the same times, body composition was assessed by bioelectrical impedance as well as appetite sensations using a visual analog scale. At the end of the intervention, the adolescents had lost body weight and FM (expressed both in kg and %) (pexercise, after the 3-week intervention, plasma leptin concentration decreased significantly (pghrelin, GH, and IGF-I) and metabolic parameters (glucose and NEFA) did not change. Interestingly, appetite was not affected by the intervention. This 3-week multidisciplinary intervention in obese adolescents induced a significant body weight loss with beneficial changes in body composition. However, despite there being no change in metabolic parameters and ghrelin in response to meals and exercise after the intervention, plasma concentrations of leptin were decreased. The failure of ghrelin levels to increase by this approach might explain the good control of appetite observed at the end of the study.

  15. Oxyntomodulin increases the concentrations of insulin and glucose in plasma but does not affect ghrelin secretion in Holstein cattle under normal physiological conditions.

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    ThanThan, S; Zhao, H; Yannaing, S; Ishikawa, T; Kuwayama, H

    2010-10-01

    Ghrelin, the natural ligand of the growth hormone secretagogue receptor (GHS-R1a), has been shown to stimulate growth hormone (GH) secretion. Regulation of ghrelin secretion in ruminants is not well studied. We investigated the effects of oxyntomodulin (OXM) and secretin on the secretions of ghrelin, insulin, glucagon, glucose, and nonesterified fatty acids (NEFA) in pre-ruminants (5 wk old) and ruminants (10 wk old) under normal physiological (feeding) conditions. Eight male Holstein calves (pre-ruminants: 52 +/- 1 kg body weight [BW]; and ruminants: 85 +/- 1 kg BW) were injected intravenously with 30 microg of OXM/kg BW, 50 microg of secretin/kg BW, and vehicle (0.1% bovine serum albumin [BSA] in saline as a control) in random order. Blood samples were collected, and plasma hormones and metabolites were analyzed using a double-antibody radioimmunoassay system and commercially available kits, respectively. We found that OXM increased the concentrations of insulin and glucose but did not affect the concentrations of ghrelin in both pre-ruminants and ruminants and that there was no effect of secretin on the concentrations of ghrelin, insulin, and glucose in these calves. We also investigated the dose-response effects of OXM on the secretion of insulin and glucose in 8 Holstein steers (401 +/- 1 d old, 398 +/- 10 kg BW). We found that OXM increased the concentrations of insulin and glucose even at physiological plasma concentrations, with a minimum effective dose of 0.4 microg/kg for the promotion of glucose secretion and 2 microg/kg for the stimulation of insulin secretion. These findings suggest that OXM takes part in glucose metabolism in ruminants.

  16. The acute effects of intermittent treadmill running on hunger and plasma acylated ghrelin concentration in individuals with obesity

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    Gholipour M

    2011-05-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Body weight is regulated by both food intake and energy expenditure. Ghrelin, a hormone produced by the stomach and pancreas, enhances appetite. This study was undertaken to determine the effects of intermittent treadmill running on acylated ghrelin and appetite in individuals with obesity."n"nMethods : Nine inactive male students, with a mean age of 20.56±0.48 yrs, a body mass index of 32.68±0.84 kg/m2 and a maximum oxygen uptake of 34.21±1.48 ml/kg/min, participated in the study in two trials (control and exercise in a counterbalanced, randomized design. The protocol included intermittent running with a constant intensity at 65% of VO2 max on a treadmill. Blood samples were collected before, during, and 2h after cessation of the exercise."n"nResults : Acylated ghrelin concentrations and hunger ratings decreased significantly in the second phase and remained lower than baseline (P=0.006 and P=0.002, respectively at the end of the exercise. The total area under the curve values and hunger ratings (all P<0.0005 were significantly lower in the exercise trial compared with the control state. Similarly, growth hormone rose significantly at the second phase and remained higher than baseline (P=0.033 at the

  17. Comparison of a high-carbohydrate and high-protein breakfast effect on plasma ghrelin, obestatin, NPY and PYY levels in women with anorexia and bulimia nervosa

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    Sedlackova Dana

    2012-06-01

    Full Text Available Abstract Background The present study investigated plasma levels of gut-brain axis peptides ghrelin, obestatin, NPY and PYY after consumption of a high-carbohydrate (HC and high-protein (HP breakfast in patients with anorexia nervosa, bulimia nervosa and in healthy controls. These peptides play an important role in regulation of energy homeostasis and their secretion is disturbed under condition of eating disorders. As various types of consumed macronutrients may induce different plasma hormone responses, so we examined these responses in women patients with eating disorders and compared them with those of healthy controls. Methods We examined plasma hormone responses to HC and HP breakfast in patients with AN (n = 14; age: 24.6 ± 1.8 years, BMI: 15.3 ± 0.7, BN (n = 15; age: 23.2 ± 1.7 years, BMI: 20.5 ± 0.9 and healthy controls (n = 14; age: 24.9 ± 1.4 years, BMI: 21.1 ± 0.8. Blood samples were drawn from the cubital vein, the first blood drawn was collected before meal, and then 30, 60, 90, 120 and 150 min after breakfast consumption. Plasma hormone levels were determined by commercially available RIA kits. Results Fasting and postprandial plasma obestatin levels were significantly increased in both AN and BN patients, while plasma ghrelin levels were significantly increased in AN patients only. After breakfast consumption, plasma levels of ghrelin and obestatin decreased, although they were still above the range of values of healthy controls. Fasting NPY plasma levels were significantly increased in AN and BN patients and did not change postprandially. Fasting PYY levels were comparable in AN, BN and healthy controls, but postprandially significantly increased after HP breakfast in AN and BN patients. Different reactions to breakfast consumption was found for ghrelin and PYY among investigated groups, while for obestatin and NPY these reactions were similar in all groups. Conclusions Significant

  18. Influence of Helicobacter pylori infection on ghrelin levels in children

    Institute of Scientific and Technical Information of China (English)

    Zhao-Hui Deng; Bo Chu; Ya-Zhen Xu; Bin Zhang; Li-Rong Jiang

    2012-01-01

    AIM:To compare ghrelin levels in plasma and gastric mucosa before and after Helicobacter pylori (H.pylori)treatment in children with H.pylori-associated functional dyspepsia.METHODS:Children with H.pylori-associated functional dyspepsia were enrolled in this study.H.pylori infection was confirmed by positive bacterial culture results.All of the children received triple H.pylori eradication therapy (a 2 wk course of omeprazole,amoxicillin,and clarithromycin).The children were divided into two groups based on the success of the H.pylori treatment:group 1 (eradicated)-patients who had a negative 13C-urea breath test 2 mo after the end of therapy; and group 2 (non-eradicated)-patients who had a positive 13C-urea breath test.Plasma ghrelin,gastric ghrelin mRNA,and the body mass index were evaluated in both groups before and after the H.pylori treatment.The plasma ghrelin levels were measured by a radioimmunoassay.The expression of gastric gnrelin mRNA was determined by real-time reverse transcription polymerase chain reaction.RESULTS:A total of 50 children with H.pylori-associated functional dyspepsia were treated with triple H.pylori eradication therapy.The mean age of the children was 5.52 ± 0.83 years,and there were 28 males and 22 females.Among the 50H.pylori-positive children,30 successfully achieved eradication,and 20 did not.The mean plasma ghrelin levels of group 1 were 22.17 ± 1.73 ng/L and 26.59 ± 2.05 ng/L before and after the treatment,respectively,which was a significant increase (P =0.001).However,the mean plasma ghrelin level of group 2 before and after the H.pylori treatment was 21.34 ± 2.40 ng/L and 22.24 ± 2.10ng/L (P =0.785).The plasma ghrelin levels increased substantially after treatment in group 1 but showed only minor changes in group 2.Similarly,the gastric ghrelin mRNA expression in group 1 before treatment was 2.84 ± 0.08.After treatment,the level was 3.11± 0.65,which was significantly different (P =0.023).The gastric ghrelin m

  19. The effect of feeding frequency on insulin and ghrelin responses in human subjects

    DEFF Research Database (Denmark)

    Solomon, Thomas; Chambers, Edward S; Jeukendrup, Asker E

    2008-01-01

    Recent work shows that increased meal frequency reduces ghrelin responses in sheep. Human research suggests there is an interaction between insulin and ghrelin. The effect of meal frequency on this interaction is unknown. Therefore, we investigated the effect of feeding frequency on insulin...... and ghrelin responses in human subjects. Five healthy male volunteers were recruited from the general population: age 24 (SEM 2)years, body mass 75.7 (SEM 3.2) kg and BMI 23.8 (SEM 0.8) kg/m(2). Volunteers underwent three 8-h feeding regimens: fasting (FAST); low-frequency(two) meal ingestion (LOFREQ(MEAL......)); high-frequency (twelve) meal ingestion (HIFREQ(MEAL)). Meals were equi-energetic within trials,consisting of 64% carbohydrate, 23% fat and 13% protein. Total energy intake was equal between feeding trials. Total area under the curve for serum insulin and plasma ghrelin responses did not differ between...

  20. Plasma kisspeptin and ghrelin levels are independently correlated with physical activity in patients with anorexia nervosa.

    Science.gov (United States)

    Hofmann, Tobias; Elbelt, Ulf; Haas, Verena; Ahnis, Anne; Klapp, Burghard F; Rose, Matthias; Stengel, Andreas

    2017-01-01

    While physical hyperactivity represents a frequent symptom of anorexia nervosa and may have a deleterious impact on the course of the disease, the underlying mechanisms are poorly understood. Since several food intake-regulatory hormones affect physical activity, the aim of the study was to investigate the association of physical activity with novel candidate hormones (kisspeptin, ghrelin, oxyntomodulin, orexin-A, FGF-21, R-spondin-1) possibly involved in patients with anorexia nervosa. Associations with psychometric parameters and body composition were also assessed. We included 38 female anorexia nervosa inpatients (body mass index, BMI, mean ± SD: 14.8 ± 1.7 kg/m(2)). Physical activity was evaluated using portable armband devices, body composition by bioelectrical impedance analysis. Blood withdrawal (hormones measured by ELISA) and psychometric assessment of depressiveness (PHQ-9), anxiety (GAD-7), perceived stress (PSQ-20) and disordered eating (EDI-2) were performed at the same time. Patients displayed a broad spectrum of physical activity (2479-26,047 steps/day) which showed a negative correlation with kisspeptin (r = -0.41, p = 0.01) and a positive association with ghrelin (r = 0.42, p = 0.01). The negative correlation with oxyntomodulin (r = -0.37, p = 0.03) was lost after consideration of potential confounders by regression analysis. No correlations were observed between physical activity and orexin-A, FGF-21 and R-spondin-1 (p > 0.05). Kisspeptin was positively correlated with BMI and body fat mass and negatively associated with the interpersonal distrust subscale of the EDI-2 (p  0.05). In conclusion, kisspeptin is inversely and ghrelin positively associated with physical activity as measured by daily step counts in anorexia nervosa patients suggesting an implication of these peptide hormones in the regulation of physical activity in anorexia nervosa. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Endocrine impact of Helicobacter pylori : Focus on ghrelin and ghrelin o -acyltransferase

    Institute of Scientific and Technical Information of China (English)

    Penny L Jeffery; Michael A McGuckin; Sara K Linden

    2011-01-01

    Ghrelin is predominantly produced by the gastric enteroendocrine cell compartment and is octanoylated by the recently discovered ghrelin o -acyltransferase (GOAT) before secretion into the bloodstream. This octanoylation is essential for many of the biological properties of ghrelin including appetite stimulation and anti-inflammatory properties as only the acylated form of ghrelin binds to the ghrelin receptor, the growth hormone secretagogue receptor (GHS-R). Given the gastric location of ghrelin production, it is perhaps not surprising that insult to the gastric mucosa affects circulating ghrelin levels in humans. Helicobacter pylori (H. pylori ) infects more than fifty percent of the world's population and once established within the gastric mucosa, can persist for life. Infection is associated with chronic gastritis, gastric atrophy and ulceration, reduced appetite and a lower body mass index (BMI). The large majority of studies investigating levels of circulating ghrelin and ghrelin expression in the stomach in patients with H. pylori infection indicate that the bacterium has a negative impact on ghrelin production and/or secretion. Eradication of infection restores ghrelin, improves appetite and increases BMI in some studies, however, a causative relationship between H. pylori -associated serum ghrelin decline and food intake and obesity has not been established. Most studies measure total ghrelin in the circulation although the measurement of the ratio of acyl/total ghrelin gives a clearer indication that the ghrelin acylation process is altered during infection and atrophy. GOAT is essential for the production of biologically-active, acyl ghrelin and the impact of H. pylori on GOAT expression and activity will be highly informative in the future.

  2. Impact of sustained weight loss achieved through Roux-en-Y gastric bypass or a lifestyle intervention on ghrelin, obestatin, and ghrelin/obestatin ratio in morbidly obese patients.

    Science.gov (United States)

    Martins, Catia; Kjelstrup, Louise; Mostad, Ingrid L; Kulseng, Bård

    2011-06-01

    Appetite-regulating hormones seem to play an important role in weight loss after bariatric surgery. Less is known regarding long-term weight loss maintenance. The objective of the study was to evaluate ghrelin and obestatin levels following long-term weight loss achieved through bariatric surgery or a lifestyle intervention in morbidly obese patients. The study was cross-sectional in design carried out in a university research center setting. The participants were weight-stable morbidly obese patients who had undergone, on average, 3 years ago, Roux-en-Y gastric bypass (RYGB) surgery (n=9) or a lifestyle weight loss intervention (n=8), and patients on a waiting list for bariatric surgery (control group; n=9). The main outcome measures were fasting/postprandial plasma levels of total ghrelin and obestatin and ghrelin/obestatin ratio. Fasting ghrelin and obestatin plasma levels were significantly elevated in the RYGB, but not in the lifestyle group, as compared with the control group. There was no statistical significant difference in fasting ghrelin/obestatin ratio among study groups. Ghrelin levels were suppressed after breakfast in all groups, with no significant differences in postprandial levels overtime between them. Obestatin levels did not change postprandially in any of the groups, but the area under the curve was significantly higher in the RYGB than in the control group. Sustained weight loss maintenance seems to be associated with increased fasting levels of ghrelin and obestatin after RYGB surgery, but not after a lifestyle intervention, while maintaining ghrelin/obestatin ratio. Ghrelin is, therefore, unlikely to contribute to weight loss maintenance after RYGB, and other mechanisms are probably involved.

  3. Abnormal ghrelin secretion contributes to gastrointestinal symptoms in multiple system atrophy patients

    OpenAIRE

    Ozawa, Tetsutaro; Tokunaga, Jun; Arakawa, Musashi; Ishikawa, Atsushi; Takeuchi, Ryoko; Mezaki, Naomi; Miura, Takeshi; Sakai, Naoko; Hokari, Mariko; Takeshima, Akari; Utsumi, Kota; Kondo, Takashi; Yokoseki, Akio; Nishizawa, Masatoyo

    2013-01-01

    Patients with multiple system atrophy (MSA) often have evidence of compromised gastrointestinal motility. Ghrelin is a gut hormone that influences gastrointestinal motility in humans. The aim of this study was to determine whether ghrelin secretion is affected in MSA patients, and to investigate the relation between ghrelin secretion and gastrointestinal symptoms. Plasma levels of active ghrelin and unacylated ghrelin were measured in patients with MSA (n = 30), other atypical parkinsonian di...

  4. The role of ghrelin in the organism

    Directory of Open Access Journals (Sweden)

    Beata Polińska

    2011-01-01

    Full Text Available Ghrelin was discovered in 1999 as an endogenous ligand of the growth hormone secretagogue receptor (GHS-R. About 60–70�0of ghrelin in the blood is released from oxyntic cells (X/A-like cells of the stomach body and fundus. Ghrelin acts via interactions with specific receptors located, for example, in the hypothalamus, pituitary gland, pancreas, kidneys, myocardium, blood vessels, adipose tissue, ovaries and placenta. Ghrelin is directly related to the control of energy balance through appetite stimulation, food intake increase and meal initiation as well as reduction of adipose tissue utilization. Moreover, ghrelin increases hydrochloric acid secretion and gastrin release, controls gastric motility, and also protects the mucous membrane of the stomach and intestine. Besides its effects on the gastrointestinal tract, ghrelin influences the cardiovascular system, bone metabolism, insulin secretion, gonad function and the immune system. It exerts anti-inflammatory effects and inhibits apoptosis of cardiomyocytes and endothelium. The plasma ghrelin level depends on the nutrition level and lifestyle factors. This article describes the most important functions of ghrelin in the organism.

  5. Ghrelin directly stimulates glucagon secretion from pancreatic alpha-cells.

    Science.gov (United States)

    Chuang, Jen-Chieh; Sakata, Ichiro; Kohno, Daisuke; Perello, Mario; Osborne-Lawrence, Sherri; Repa, Joyce J; Zigman, Jeffrey M

    2011-09-01

    Previous work has demonstrated that the peptide hormone ghrelin raises blood glucose. Such has been attributed to ghrelin's ability to enhance GH secretion, restrict insulin release, and/or reduce insulin sensitivity. Ghrelin's reported effects on glucagon have been inconsistent. Here, both animal- and cell-based systems were used to determine the role of glucagon in mediating ghrelin's effects on blood glucose. The tissue and cell distribution of ghrelin receptors (GHSR) was evaluated by quantitative PCR and histochemistry. Plasma glucagon levels were determined following acute acyl-ghrelin injections and in pharmacological and/or transgenic mouse models of ghrelin overexpression and GHSR deletion. Isolated mouse islets and the α-cell lines αTC1 and InR1G9 were used to evaluate ghrelin's effects on glucagon secretion and the role of calcium and ERK in this activity. GHSR mRNA was abundantly expressed in mouse islets and colocalized with glucagon in α-cells. Elevation of acyl-ghrelin acutely (after sc administration, such that physiologically relevant plasma ghrelin levels were achieved) and chronically (by slow-releasing osmotic pumps and as observed in transgenic mice harboring ghrelinomas) led to higher plasma glucagon and increased blood glucose. Conversely, genetic GHSR deletion was associated with lower plasma glucagon and reduced fasting blood glucose. Acyl-ghrelin increased glucagon secretion in a dose-dependent manner from mouse islets and α-cell lines, in a manner requiring elevation of intracellular calcium and phosphorylation of ERK. Our study shows that ghrelin's regulation of blood glucose involves direct stimulation of glucagon secretion from α-cells and introduces the ghrelin-glucagon axis as an important mechanism controlling glycemia under fasting conditions.

  6. Comparative study on ghrelin level change and its related factors in hypertensive elders with psychological distress

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To investigate the change of plasma ghrelin level and explore the related factors of ghrelin alteration in elderly hypertensive patients with psychological distress.Methods A total of 300 elders,who were screened with Hamilton Anxiety Scale(HAMA),Hamilton Rating Scale for Depression(HAMD),and the Symptom Checklist-90(SCL-90)for psychological stress and somato-psychological manifestations respectively,were divided into hypertension group(n=148)and non-hypertension group(n=152).Their blood samples w...

  7. Acute effects of ghrelin administration on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Vestergaard, Esben Thyssen; Djurhuus, Christian Born; Gjedsted, Jakob;

    2007-01-01

    CONTEXT: Ghrelin infusion increases plasma glucose and nonesterified fatty acids, but it is uncertain whether this is secondary to the concomitant release of GH. OBJECTIVE: Our objective was to study direct effects of ghrelin on substrate metabolism. DESIGN: This was a randomized, single-blind, p......CONTEXT: Ghrelin infusion increases plasma glucose and nonesterified fatty acids, but it is uncertain whether this is secondary to the concomitant release of GH. OBJECTIVE: Our objective was to study direct effects of ghrelin on substrate metabolism. DESIGN: This was a randomized, single...

  8. Fat mass and obesity-associated gene (FTO) is linked to higher plasma levels of the hunger hormone ghrelin and lower serum levels of the satiety hormone leptin in older adults.

    Science.gov (United States)

    Benedict, Christian; Axelsson, Tomas; Söderberg, Stefan; Larsson, Anders; Ingelsson, Erik; Lind, Lars; Schiöth, Helgi B

    2014-11-01

    The mechanisms through which common polymorphisms in the fat mass and obesity-associated gene (FTO) drive the development of obesity in humans are poorly understood. Using cross-sectional data from 985 older people (50% females) who participated at age 70 years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), circulating levels of ghrelin and leptin were measured after an overnight fast. In addition, subjects were genotyped for FTO rs17817449 (AA, n = 345 [35%]; AC/CA, n = 481 [48.8%]; CC, n = 159 [16.1%]). Linear regression analyses controlling for sex, self-reported physical activity level, fasting plasma glucose, and BMI were used. A positive relationship between the number of FTO C risk alleles and plasma ghrelin levels was found (P = 0.005; relative plasma ghrelin difference between CC and AA carriers = ∼ 9%). In contrast, serum levels of the satiety-enhancing hormone leptin were inversely linked to the number of FTO C risk alleles (P = 0.001; relative serum leptin difference between CC and AA carriers = ∼ 11%). These associations were also found when controlling for waist circumference. The present findings suggest that FTO may facilitate weight gain in humans by shifting the endocrine balance from the satiety hormone leptin toward the hunger-promoting hormone ghrelin.

  9. Ghrelin and Ghrelin Receptor Modulation of Psychostimulant Action

    Directory of Open Access Journals (Sweden)

    Paul Jeff Wellman

    2013-09-01

    Full Text Available Ghrelin (GHR is an orexigenic gut peptide that modulates multiple homeostatic functions including gastric emptying, anxiety, stress, memory, feeding and reinforcement. GHR is known to bind and activate growth-hormone secretagogue receptors (termed GHR-Rs. Of interest to our laboratory has been the assessment of the impact of GHR modulation of the locomotor activation and reward/reinforcement properties of psychostimulants such as cocaine and nicotine. Systemic GHR infusions augment cocaine stimulated locomotion and conditioned place preference (CPP in rats, as does food restriction which elevates plasma ghrelin levels. Ghrelin enhancement of psychostimulant function may occur owing to a direct action on mesolimbic dopamine function or may reflect an indirect action of ghrelin on glucocorticoid pathways. Genomic or pharmacological ablation of GHR-Rs attenuates the acute locomotor-enhancing effects of nicotine, cocaine, amphetamine and alcohol and blunts the CPP induced by food, alcohol, amphetamine and cocaine in mice. The stimulant nicotine can induce CPP and like amphetamine and cocaine, repeated administration of nicotine induces locomotor sensitization in rats. Inactivation of ghrelin circuit function in rats by injection of a ghrelin receptor antagonist (e.g. JMV 2959 diminishes the development of nicotine-induced locomotor sensitization. These results suggest a key permissive role for GHR-R activity for the induction of locomotor sensitization to nicotine. Our finding that GHR-R null rats exhibit diminished patterns of responding for intracranial self-stimulation complements an emerging literature implicating central GHR circuits in drug reward/reinforcement. Finally, antagonism of GHR-Rs may represent a smoking cessation modality that not only blocks nicotine-induced reward but that also may limit weight gain after smoking cessation.

  10. Effects of glucose and amino acids on ghrelin secretion in sheep.

    Science.gov (United States)

    Sugino, Toshihisa; Kawakita, Yuko; Fukumori, Rika; Hasegawa, Yoshihisa; Kojima, Masayasu; Kangawa, Kenji; Obitsu, Taketo; Taniguchi, Kohzo

    2010-04-01

    Two experiments were conducted to elucidate the effects of post-ruminal administration of starch and casein (Exp. 1), plasma amino acids concentrations (Exp. 2), and plasma glucose and insulin concentrations (Exp. 2) on plasma ghrelin concentrations in sheep. In Exp. 1, plasma ghrelin concentrations were determined by four infusion treatments (water, cornstarch, casein and cornstarch plus casein) in four wethers. Abomasal infusion of casein increased plasma alpha-amino N (AAN) concentrations. Infusion of starch or casein alone did not affect plasma ghrelin concentrations, but starch plus casein infusion increased plasma levels of ghrelin, glucose and AAN. In Exp 2, we investigated the effects of saline or amino acids on ghrelin secretion in four wethers. Two hours after the initiation of saline or amino acid infusion into the jugular vein, glucose was also continuously infused to investigate the effects of blood glucose and insulin by hyper-glycemic clump on plasma ghrelin concentrations. Infusion of amino acids alone raised plasma levels of ghrelin, but the higher plasma glucose and insulin concentrations had no effect on plasma ghrelin concentrations. These results suggest that high plasma levels of amino acids can stimulate ghrelin secretion, but glucose and insulin do not affect ghrelin secretion in sheep.

  11. Glucagon-like peptide 2 inhibits ghrelin secretion in humans

    DEFF Research Database (Denmark)

    Banasch, Matthias; Bulut, Kerem; Hagemann, Dirk;

    2006-01-01

    INTRODUCTION: The growth hormone secretagogue receptor ligand ghrelin is known to play a pivotal role in the central nervous control of energy homeostasis. Circulating ghrelin levels are high under fasting conditions and decline after meal ingestion, but the mechanisms underlying the postprandial...... drop in ghrelin levels are poorly understood. In the present study we addressed, whether (1) exogenous GLP-2 administration decreases ghrelin levels and (2) what other endogenous factors are related to ghrelin secretion under fasting conditions. PATIENTS AND METHODS: Fifteen healthy male volunteers...... were studied with the intravenous infusion of GLP-2 (2 pmol l(-1) min(-1)) or placebo over 120 min in the fasting state. Plasma concentrations of glucose, insulin, C-peptide, glucagon, intact GLP-2 and ghrelin were determined. RESULTS: During the infusion of GLP-2, plasma concentrations of intact GLP-2...

  12. Assessment of ghrelin and leptin receptor levels in postmenopausal women who received oral or transdermal menopausal hormonal therapy

    Institute of Scientific and Technical Information of China (English)

    Barbara RUSZKOWSKA; Alina SOKUP; Arleta KULWAS; Maciej W.SOCHA; Krzysztof GˊORALCZYK; Barbara GˊORALCZYK; Danuta ROˊSˊC

    2012-01-01

    Objective:In postmenopausal women,an increased leptin concentration and reduced levels ofghrelin and adiponectin were observed.The aim of this study was to evaluate the concentrations of the active form of ghrelin,total ghrelin,leptin receptor,lipoprotein(a) (Lp(a)),and plasminogen activator inhibitor type 1 (PAI-1) in postmenopausal women who received oral or transdermal menopausal hormonal therapy (MHT).Methods:The study involved 76 healthy women:46 women aged from 44 to 58 years who received oral (26) or transdermal (20) MHT; the control group consisted of 30 women aged from 44 to 54 years who did not receive MHT.The plasma concentrations of total ghrelin,the active form of ghrelin,Lp(a),and PAI-1:Ag were measured by enzyme-linked immunosorbent assay (ELISA).The concentration of the leptin receptor was measured by enzyme immunometric assay (EIA).Results:We observed a significantly higher concentration of total ghrelin and the active form of ghrelin in women who received transdermal MHT in comparison with those who took oral MHT.We also found a significantly lower concentration of total ghrelin in women who received oral MHT compared with the control group.A higher concentration of PAI-1:Ag was found in the group of women who took transdermal MHT in comparison with those who took oral MHT and with the control group.The differences were statistically significant.Additionally,we found a significant negative correlation between the concentrations of total ghrelin and PAI-1:Ag and a positive correlation between the concentrations of total ghrelin and leptin receptor in women who received transdermal MHT.Conclusions:The study showed that women who used transdermal MHT had higher levels of total ghrelin than women who took oral MHT.This indicates a beneficial effect of the transdermal route of MHT.However,transdermal therapy was associated with adverse effects with regard to the observed higher levels of PAI-1:Ag,which in turn,can lead to a reduction in fibrinolytic

  13. Tissue distribution and effects of fasting and obesity on the ghrelin axis in mice.

    Science.gov (United States)

    Morash, Michael G; Gagnon, Jeffrey; Nelson, Stephanie; Anini, Younes

    2010-08-09

    Ghrelin is a 28 amino acid peptide hormone derived from the 117 amino acid proghrelin, following cleavage by proprotein convertase 1 (PC1). In this study, we comprehensively assessed the tissue distribution and the effect of fasting and obesity on preproghrelin, Exon-4D, PC1 and GOAT expression and proghrelin-derived peptide (PGDP) secretion. The stomach was the major source of preproghrelin expression and PDGPs, followed by the small intestine. The remaining peripheral tissues (including the brain and pancreas) contained negligible expression levels. We detected obestatin in all stomach proghrelin cells, however, 22% of proghrelin cells in the small intestine did not express obestatin. There were strain differences in ghrelin secretion in response to fasting between CD1 and C57BL/6 mice. After a 24 hour-fast, CD1 mice had increased plasma levels of total ghrelin and obestatin with no change in preproghrelin mRNA or PGDP tissues levels. C57BL/6 mice showed a different response to a 24 hour-fast having increased proghrelin mRNA expression, stomach acylated ghrelin peptide and no change in plasma obestatin in C57BL/6 mice. In obese mice (ob/ob and diet-induced obesity (DIO)) there was a significant increase in preproghrelin mRNA levels while tissue and plasma PGDP levels were significantly reduced. Fasting did not affect PGDP in obese mice. Obese models displayed differences in GOAT expression, which was elevated in DIO mice, but reduced in ob/ob mice. We did not find co-localization of the leptin receptor in ghrelin expressing stomach cells, ruling out a direct effect of leptin on stomach ghrelin synthesis and secretion.

  14. Carob pulp preparation rich in insoluble dietary fiber and polyphenols enhances lipid oxidation and lowers postprandial acylated ghrelin in humans.

    Science.gov (United States)

    Gruendel, Sindy; Garcia, Ada L; Otto, Baerbel; Mueller, Corinna; Steiniger, Jochen; Weickert, Martin O; Speth, Maria; Katz, Norbert; Koebnick, Corinna

    2006-06-01

    Ghrelin is an orexigenic hormone that may affect substrate utilization in humans. Ghrelin is influenced by macronutrients, but the effects of insoluble dietary fiber and polyphenols are unknown. We investigated the effects of a polyphenol-rich insoluble dietary fiber preparation from carob pulp (carob fiber) on postprandial ghrelin responses and substrate utilization. Dose-dependent effects of the consumption of carob fiber were investigated in a randomized, single-blind, crossover study in 20 healthy subjects, aged 22-62 y. Plasma total and acylated ghrelin, triglycerides, and serum insulin and nonesterified fatty acids (NEFA) levels were repeatedly assessed before and after ingestion of an isocaloric standardized liquid meal with 0, 5, 10, or 20 g of carob fiber over a 300-min period. The respiratory quotient (RQ) was determined after consumption of 0 or 20 g of carob fiber. Carob fiber intake lowered acylated ghrelin to 49.1%, triglycerides to 97.2%, and NEFA to 67.2% compared with the control meal (P fiber-enriched liquid meal. Postprandial energy expenditure was increased by 42.3% and RQ was reduced by 99.9% after a liquid meal with carob fiber compared with a control meal (P pulp preparation, an insoluble dietary fiber rich in polyphenols, decreases postprandial responses of acylated ghrelin, triglycerides, and NEFA and alters RQ, suggesting a change toward increased fatty acid oxidation. These results indicate that carob fiber might exert beneficial effects in energy intake and body weight.

  15. Effect of Ghrelin on Glucose-Insulin Homeostasis: Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Susana Sangiao-Alvarellos

    2010-01-01

    Full Text Available Ghrelin is a 28-amino-acid peptide that displays a strong growth hormone- (GH- releasing activity through the activation of the growth hormone secretagogue receptor (GHSR. The first studies about role of ghrelin were focused on its orexigenic ability, but despite indisputable pharmacological data, the evidence for a physiological role for ghrelin in the control of appetite is much less clear. Mice with targeted deletion of either ghrelin or the GHSR exhibit an essentially normal metabolic phenotype when fed a regular chow diet, suggesting that ghrelin may have a redundant role in the regulation of food intake. RNAs for ghrelin as well as GHSR are expressed in the pancreas of rats and humans and several studies propose that ghrelin could have an important function in glucose homeostasis and insulin release, independent of GH secretion. Low plasma ghrelin levels are associated with elevated fasting insulin levels and insulin resistance, suggesting both physiological and pathophysiological roles for ghrelin. For this reason, at least theoretically, ghrelin and/or its signalling manipulation could be useful for the treatment or prevention of diseases of glucose homeostasis such as type 2 diabetes.

  16. The Sweetener-Sensing Mechanisms of the Ghrelin Cell

    Science.gov (United States)

    Steensels, Sandra; Vancleef, Laurien; Depoortere, Inge

    2016-01-01

    Carbohydrate administration decreases plasma levels of the ‘hunger hormone’ ghrelin. The ghrelin cell is co-localized with the sweet taste receptor subunit, TAS1R3, and the gustatory G-protein, gustducin, both involved in the sensing of sweeteners by entero-endocrine cells. This study investigated the role of gustducin-mediated sweet taste receptor signaling on ghrelin secretion in a gastric ghrelinoma cell line, tissue segments and mice. The monosaccharide d-glucose and low-intensity sweetener oligofructose (OFS) decreased (p sweetener sucralose increased (p sweeteners by the ghrelin cell. PMID:27941594

  17. The effect of neonatal maternal stress on plasma levels of adrenocorticotropic hormone, corticosterone, leptin, and ghrelin in adult male rats exposed to acute heterotypic stressor.

    Science.gov (United States)

    Holubová, A; Štofková, A; Jurčovičová, J; Šlamberová, R

    2016-12-22

    Activation of the hypothalamic-pituitary-adrenal (HPA) axis is important for maintenance of homeostasis during stress. Recent studies have shown a connection between the HPA axis and adipose tissue. The present study investigated the effect of acute heterotypic stress on plasma levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), leptin, and ghrelin in adult male rats with respect to neonatal maternal social and physical stressors. Thirty rat mothers and sixty of their male progeny were used. Pups were divided into three groups: unstressed control (C), stressed by maternal social stressor (S), stressed by maternal social and physical stressors (SW). Levels of hormones were measured in adult male progeny following an acute swimming stress (10 min) or no stress. ELISA immunoassay was used to measured hormones. The ACTH and CORT levels were significantly increased in all groups of adult progeny after acute stress; however, CORT levels were significantly lower in both neonatally stressed groups compared to controls. After acute stress, plasma leptin levels were decreased in the C and SW groups but increased in the S group. The data suggest that long-term neonatal stressors lead to lower sensitivity of ACTH receptors in the adrenal cortex, which could be a sign of stress adaptation in adulthood. Acute stress in adult male rats changes plasma levels of leptin differently relative to social or physical neonatal stressors.

  18. Interferon-γ inhibits ghrelin expression and secretion via a somatostatin-mediated mechanism

    Institute of Scientific and Technical Information of China (English)

    Jesper AB Strickertsson; Kristina BV Dφssing; Anna JM Aabakke; Hans-Olof Nilsson; Thomas VO Hansen; Ulrich Knigge; Andreas Kj(ae)r; Torkel Wadstr(o)m; Lennart Friis-Hansen

    2011-01-01

    AIM: To investigate if and how the proinflammatory cytokine interferon γ (IFNγ) affects ghrelin expression in mice. METHODS: The plasma concentration of ghrelin, and gastric ghrelin and somatostatin expression, were examined in wild-type mice and mice infected with Helicobacter pylori (H. pylori ). Furthermore, ghrelin expression was examined in two achlorhydric mouse models with varying degrees of gastritis due to bacterial overgrowth. To study the effect of IFNγ alone, mice were given a subcutaneous infusion of IFNγ for 7 d. Finally, the influence of IFNγ and somatostatin on the ghrelin promoter was characterized. RESULTS: H. pylori infection was associated with a 50% reduction in ghrelin expression and plasma concentration. Suppression of ghrelin expression was inversely correlated with gastric inflammation in achlorhdyric mouse models. Subcutaneous infusion of IFNγ suppressed fundic ghrelin mRNA expression and plasma ghrelin concentrations. Finally, we showed that the ghrelin promoter operates under the control of somatostatin but not under that of IFNγ. CONCLUSION: Gastric infection and inflammation is associated with increased IFNγ expression and reduced ghrelin expression. IFNγ does not directly control ghrelin expression but inhibits it indirectly via somatostatin.

  19. 冠心病糖代谢异常患者血浆Ghrelin水平及临床意义%Plasma ghrelin level in patients with coronary heart disease with abnormal glucose metabolism and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    庞军刚; 徐新; 唐良秋; 张社兵; 江志平

    2012-01-01

    目的:探讨冠心病糖代谢异常患者血浆胃饥饿素(Ghrelin)水平及其相关临床意义.方法:将纳入研究对象依据相关检验及检查结果分为正常对照组、冠心病组(冠心病糖代谢正常组和冠心病糖代谢异常组)、单纯糖代谢异常组.收集所有入选对象人院第2天清晨空腹血样,采用ELISA方法同批检测血浆Ghrelin水平.结果:①冠心病组及单纯糖代谢异常组血浆Ghrelin水平均显著低于正常对照组.②冠心病糖代谢异常组血浆Ghrelin水平显著低于冠心病糖代谢正常组及单纯糖代谢异常组.③析因分析结果显示:冠心病与糖代谢异常在对血浆Ghrelin水平影响方面不存在交互作用.然而,糖代谢异常比冠心病对血浆Ghrelin水平的影响更明显.结论:冠心病糖代谢异常患者血浆Ghrelin水平显著下降,且糖代谢异常对Ghrelin的影响更明显.%AIM: To study plasma ghrelin level distribution in patients with coronary heart disease (CHD) with abnormal glucose metabolism and to discuss its clinical significance. METHODS; According to laboratory examination results, subjects were divided into control group, coronary heart disease with normal glucose metabolism group, coronary heart disease with abnormal glucose metabolism group and abnormal glucose metabolism group. Fasting blood samples were collected the morning after admission with EDTA-2K anticoagulation tubes. Blood samples were then transferred to centrifuge tubes containing aprotinin and were centrifuged to extract plasma for cryopreservation. All blood plasma ghrelin levels were tested with ELISA. RESULTS: Compared with those in control group, ghrelin levels were significantly reduced in the group with CHD with normal glucose metabolism, group of CHD with abnormal glucose metabolism and group with abnormal glucose metabolism. Compared with those in the group of CHD with normal glucose metabolism, levels of ghrelin were significantly reduced in patients with

  20. Estimation of gastric ghrelin-positive cells activity in hyperthyroid rats.

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    Maria M Winnicka

    2009-01-01

    Full Text Available Ghrelin is a peptide of 28 amino acids that transmits appetite related signals from peripheral organs to the brain. The main source of ghrelin is stomach. The regulation of ghrelin secretion is still unknown. The finding that fasting and food intake, respectively increase and decrease the secretion of ghrelin suggests that this hormone may be a bridge connecting somatic growth with energy metabolism and appears to play an important role in the alteration of energy homeostasis and body weight in pathophisiological conditions. The purpose of this study was the evaluation of gastric ghrelin immunoreactivity and ghrelin plasma concentration in male Wistar rats with hyperthyroidism. Experimental model of hyperthyroidism was induced by intraperitoneal injection of levothyroxine at the dose of 80 microg/kg daily over 21 days. At the end of experiment the animals were anaesthetized, blood was taken from abdominal aorta to determinate plasma ghrelin concentration by RIA and then the animals underwent resection of distal part of stomach. Immunohistochemical study were performed using monoclonal specific antybodies against ghrelin. Hyperthyroidism was a reason of increase of gastric mucosal ghrelin - immunoreactivity, accompanied by a significant decreased of ghrelin plasma concentration. Those observations may indicate, that chronic administration of L-thyroxine cause the change of ghrelin plasma concentration in rats, probably via direct influence on gastric X/A-like cells, but this effect is not responsible for hyperphagia associated with hyperthyroidism.

  1. Modulation of Ingestive Behavior and Gastrointestinal Motility by Ghrelin in Diabetic Animals and Humans

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    Chih-Yen Chen

    2010-05-01

    Full Text Available Acyl ghrelin, a 28-amino acid peptide hormone, is the endogenous cognate ligand for the growth hormone secretagogue receptor. Ghrelin is involved in stimulating growth hormone release, eliciting feeding behavior, inducing adiposity and stimulating gastrointestinal motility. Ghrelin is unique for its post-translational modification of O-n-octanoylation at serine 3 through ghrelin O-acyltransferase, and is the only peripheral signal to enhance food intake. Plasma ghrelin levels manifest “biphasic changes” in diabetes mellitus (DM. In the early stage of DM, the stomach significantly increases the secretion of ghrelin into the plasma, and elevated plasma ghrelin levels are correlated with diabetic hyperphagic feeding and accelerated gastrointestinal motility. In the late stage of DM, plasma ghrelin levels may be lower, which might be linked with anorexia/muscle wasting, delayed gastrointestinal transit, and even gastroparesis. Therefore, the unique ghrelin system may be the most important player compared to the other hindgut hormones participating in the “entero-insular axis”. Further studies using either knockdown or knockout of ghrelin gene products and ghrelin O-acyltransferase may unravel the pathogenesis of DM, and show benefits in combating this disease and metabolic syndrome.

  2. 肥胖患儿血糖、血脂与血浆生长激素释放多肽水平的关系%The relationship between plasma ghrelin levels and glucose and lipid metabolisms of child and adolescent obesity

    Institute of Scientific and Technical Information of China (English)

    张琴; 陈蔚; 赵岫; 廖建湘; 李永柏; 李成荣

    2011-01-01

    目的 探讨肥胖患儿血脂和血糖与血浆生长激素释放多肽(ghrelin)水平的关系.方法 选择年龄、性别相匹配的肥胖患儿(肥胖组)和正常体质量儿童(对照组)各30例,采用酶联免疫吸附方法检测血浆ghrelin水平;同步取血采用化学发光法测定血清胰岛素(INS)、C肽(CPE)水平;采用生化仪检测血清空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL).结果 肥胖组血浆ghrelin水平较对照组明显降低[(15.49±1.98)与(19.47±1.50)ng/ml],BMI、腰围、FBG、INS值较对照组明显增高,分别为(28.19 ±3.83)与(21.07±1.53)kg/m2、(88.60±6.13)与(78.52±4.40)cm、(5.23±0.49)与(4.59±0.63)mmol/L、(22.32±3.50)与(16.98±2.50)μIU/L,差异均有统计学意义(均P<0.01);TC值较对照组亦明显增高[(5.87±0.88)与(4.05±0.76)nmol/L].肥胖组的血浆ghrelin水平与体质量、BMI、腰围、INS、TC呈显著的负相关,(r=-0.385、-0.466、-0.336、-0.387、-0.373,均P<0.01),与FBG呈负相关,(r=-0.324,P<0.05),与年龄、身高、CPE、TG、HDL-C、LDL-C等因素无显著相关性.结论 肥胖患儿血浆ghrelin水平明显降低,并与血脂和血糖明显相关.%Objective To explore the relationship between plasma ghrelin levels and glucose and lipid metabolisms of child and adolescent obesity.Methods 30 cases of obesity and 30 healthy normal weisht children and adolescents with same age and gender were selected.Plasma ghrelin level,serum insulin(INS),C-peptide(CPE),fasting blood glucose(FBG),total cholesterol(TC),triglyceride(TG),high-density lipoproteins(HDL),low-density lipoproteins(LDL)were measured.Results For the obesity group:Plasma ghrelin level significantly decreased [(15.49±1.98)vs(19.47 ±1.50)μg/L]compared with control(P<0.05);BMI,waistline,FBG,INS were very significantly increased(28.19±3.83)vs(21.07±1.53)kg/m2;(88.60±6.13)vs(78.52 ±4.40)cm;(5.23±0.49)vs(4.59 ±0.63)mmol/L;(22.32 ±3.50)vs(16

  3. Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents.

    Science.gov (United States)

    Misra, Madhusmita; Miller, Karen K; Kuo, Kelly; Griffin, Kathryn; Stewart, Victoria; Hunter, Emily; Herzog, David B; Klibanski, Anne

    2005-08-01

    Ghrelin is an orexigenic peptide and a growth hormone (GH) secretagogue. Secretory dynamics of ghrelin have not been characterized in adolescents with anorexia nervosa (AN). We hypothesized that, compared with healthy adolescents, girls with AN would have increased ghrelin concentrations measured over 12 h of nocturnal sampling from increased basal and pulsatile secretion, and endogenous ghrelin would independently predict GH and cortisol. We examined ghrelin concentration and secretory dynamics in 22 girls with AN and 18 healthy adolescents 12-18 yr old. Associations between ghrelin, various hormones, and measures of insulin resistance were examined. On Cluster analysis, girls with AN had higher ghrelin concentrations than controls, including total area under the curve (AUC) (P = 0.002), nadir (P = 0.0006), and valley levels (P = 0.002). On deconvolution analysis, secretory burst amplitude (P = 0.03) and burst mass (P = 0.04) were higher in AN, resulting in higher pulsatile (P = 0.05) and total ghrelin secretion (P = 0.03). Fasting ghrelin independently predicted GH burst frequency (r = 0.44, P = 0.005). The nutritional markers body mass index and body fat predicted postglucose and valley ghrelin but not fasting levels. Ghrelin parameters were inversely associated with fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), leptin, and IGF-I. HOMA-IR was the most significant predictor of most ghrelin parameters. Valley ghrelin independently predicted cortisol burst frequency (52% of variability), and ghrelin parameters independently predicted total triiodothyronine and LH levels. Higher ghrelin concentrations in adolescents with AN are a consequence of increased secretory burst mass and amplitude. The most important predictor of ghrelin concentration is insulin resistance, and ghrelin in turn predicts GH and cortisol burst frequency.

  4. The Sweetener-Sensing Mechanisms of the Ghrelin Cell

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    Sandra Steensels

    2016-12-01

    Full Text Available Carbohydrate administration decreases plasma levels of the ‘hunger hormone’ ghrelin. The ghrelin cell is co-localized with the sweet taste receptor subunit, TAS1R3, and the gustatory G-protein, gustducin, both involved in the sensing of sweeteners by entero-endocrine cells. This study investigated the role of gustducin-mediated sweet taste receptor signaling on ghrelin secretion in a gastric ghrelinoma cell line, tissue segments and mice. The monosaccharide d-glucose and low-intensity sweetener oligofructose (OFS decreased (p < 0.001 ghrelin secretion while the high-intensity sweetener sucralose increased (p < 0.001 ghrelin secretion in vitro. These effects were not mediated via the sweet taste receptor or glucose transporters (the sodium-dependent glucose cotransporter SGLT-1 and GLUT2. The effect of these compounds was mimicked ex vivo in gastric and jejunal segments from both wild type (WT and α-gustducin knockout (α-gust−/− mice. In vivo, the sensing of d-glucose was polarized since intragastric but not intravenous administration of d-glucose decreased (p < 0.05 ghrelin levels in an α-gustducin independent manner which involved inhibition of duodenal ghrelin release. In contrast, neither OFS nor sucralose affected ghrelin secretion in vivo. In conclusion, α-gustducin-mediated sweet taste receptor signaling does not play a functional role in the sensing of carbohydrates, or low- or high-intensity sweeteners by the ghrelin cell.

  5. Ghrelin Is a Novel Regulator of GLP-1 Secretion.

    Science.gov (United States)

    Gagnon, Jeffrey; Baggio, Laurie L; Drucker, Daniel J; Brubaker, Patricia L

    2015-05-01

    GLP-1 is a gastrointestinal L-cell hormone that enhances glucose-stimulated insulin secretion. Hence, strategies that prevent GLP-1 degradation or activate the GLP-1 receptor are used to treat patients with type 2 diabetes. GLP-1 secretion occurs after a meal and is partly regulated by other circulating hormones. Ghrelin is a stomach-derived hormone that plays a key role in whole-body energy metabolism. Because ghrelin levels peak immediately before mealtimes, we hypothesized that ghrelin plays a role in priming the intestinal L-cell for nutrient-induced GLP-1 release. The intraperitoneal injection of ghrelin into mice 15 min before the administration of oral glucose enhanced glucose-stimulated GLP-1 release and improved glucose tolerance, whereas the ghrelin receptor antagonist D-Lys GHRP-6 reduced plasma levels of GLP-1 and insulin and diminished oral glucose tolerance. The ghrelin-mediated improvement in glucose tolerance was lost in mice coinjected with a GLP-1 receptor antagonist as well as in Glp1r(-/-) mice lacking the GLP-1 receptor. The impaired oral glucose tolerance in diet-induced obese mice was also improved by ghrelin preadministration. Importantly, ghrelin directly stimulated GLP-1 release from L-cell lines (murine GLUTag, human NCI-H716) through an extracellular signal-related kinase 1/2-dependent pathway. These studies demonstrate a novel role for ghrelin in enhancing the GLP-1 secretory response to ingested nutrients.

  6. G protein-coupled receptor 120 signaling regulates ghrelin secretion in vivo and in vitro.

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    Gong, Zhi; Yoshimura, Makoto; Aizawa, Sayaka; Kurotani, Reiko; Zigman, Jeffrey M; Sakai, Takafumi; Sakata, Ichiro

    2014-01-01

    Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is produced predominantly in the stomach. It has been reported that endogenous ghrelin levels are increased by fasting and decreased immediately after feeding and that fasting-induced ghrelin release is controlled by the sympathetic nervous system. However, the mechanisms of plasma ghrelin decrement after feeding are poorly understood. Here, we studied the control of ghrelin secretion using ghrelin-producing cell lines and found that these cells express high levels of mRNA encoding G-protein coupled receptor 120 (GPR120). Addition of GW-9508 (a GPR120 chemical agonist) and α-linolenic acid (a natural ligand for GPR120) inhibited the secretion of ghrelin by ∼50 and 70%, respectively. However, the expression levels of preproghrelin and ghrelin O-acyltransferase (GOAT) mRNAs were not influenced by GW-9508. In contrast, the expression levels of prohormone convertase 1 were decreased significantly by GW-9508 incubation. Moreover, we observed that the inhibitory effect of GW-9508 on ghrelin secretion was blocked by a small interfering RNA (siRNA) targeting the sequence of GPR120. Furthermore, pretreatment with GW-9508 blocked the effect of the norepinephrine (NE)-induced ghrelin elevation in ghrelin cell lines. In addition, we showed that GW-9508 inhibited ghrelin secretion via extracellular signal-regulated kinase activity in ghrelin cell lines. Finally, we found that GW-9508 decreased plasma ghrelin levels in mice. These results suggest that the decrease of ghrelin secretion after feeding is induced partially by long-chain fatty acids that act directly on gastric GPR120-expressing ghrelin cells.

  7. Ghrelin receptor regulates appetite and satiety during aging in mice by regulating meal frequency and portion size but not total food intake

    Science.gov (United States)

    Aging is often associated with overweight and obesity. There exists a long-standing debate about whether meal pattern also contributes to the development of obesity. The orexigenic hormone ghrelin regulates appetite and satiety by activating its receptor, growth hormone secretagogue receptor (GHS-R)...

  8. Development of a rapid, simple assay of plasma total carotenoids

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    Donaldson Michael

    2012-09-01

    Full Text Available Abstract Background Plasma total carotenoids can be used as an indicator of risk of chronic disease. Laboratory analysis of individual carotenoids by high performance liquid chromatography (HPLC is time consuming, expensive, and not amenable to use beyond a research laboratory. The aim of this research is to establish a rapid, simple, and inexpensive spectrophotometric assay of plasma total carotenoids that has a very strong correlation with HPLC carotenoid profile analysis. Results Plasma total carotenoids from 29 volunteers ranged in concentration from 1.2 to 7.4 μM, as analyzed by HPLC. A linear correlation was found between the absorbance at 448 nm of an alcohol / heptane extract of the plasma and plasma total carotenoids analyzed by HPLC, with a Pearson correlation coefficient of 0.989. The average coefficient of variation for the spectrophotometric assay was 6.5% for the plasma samples. The limit of detection was about 0.3 μM and was linear up to about 34 μM without dilution. Correlations between the integrals of the absorption spectra in the range of carotenoid absorption and total plasma carotenoid concentration gave similar results to the absorbance correlation. Spectrophotometric assay results also agreed with the calculated expected absorbance based on published extinction coefficients for the individual carotenoids, with a Pearson correlation coefficient of 0.988. Conclusion The spectrophotometric assay of total carotenoids strongly correlated with HPLC analysis of carotenoids of the same plasma samples and expected absorbance values based on extinction coefficients. This rapid, simple, inexpensive assay, when coupled with the carotenoid health index, may be useful for nutrition intervention studies, population cohort studies, and public health interventions.

  9. Effects of ghrelin in energy balance and body weight homeostasis.

    Science.gov (United States)

    Mihalache, Laura; Gherasim, Andreea; Niță, Otilia; Ungureanu, Maria Christina; Pădureanu, Sergiu Serghei; Gavril, Radu Sebastian; Arhire, Lidia Iuliana

    2016-02-01

    Ghrelin is a gut peptide composed of 28 amino acids mostly secreted in the gastric fundus mucosa. It was isolated and described in 1999 by Kojima et al. and only three years later its specific receptor, GHSR1a, was also identified. Ghrelin, the endogenous ligand for the GH secretagogue receptor, is the only peripheral orexigenic hormone that activates the receptors to be found especially in the appetite center (hypothalamus and pituitary gland). Ghrelin is present in human plasma in two forms: an inactive form known as deacylated ghrelin, and an active form called acylated ghrelin synthesized under the action of ghrelin O-acyltransferase enzyme (GOAT). The literature even mentions an extremely complex ghrelin/GOAT/GHSR system involved in the regulation of human energy, metabolism and adaptation of energy homeostasis to environmental changes. In humans, there is a preprandial rise and a postprandial fall in plasma ghrelin levels, which strongly suggest that the peptide plays a physiological role in meal initiation and may be employed in determining the amount and quality of ingested food. Besides the stimulation of food intake, ghrelin determines a decrease in energy expenditure and promotes the storage of fatty acids in adipocytes. Thus, in the human body ghrelin induces a positive energy balance, an increased adiposity gain, as well as an increase in caloric storage, seen as an adaptive mechanism to caloric restriction conditions. In the current world context, when we are witnessing an increasing availability of food and a reduction of energy expenditure to a minimum level, these mechanisms have become pathogenic. As a consequence, the hypothesis that ghrelin is involved in the current obesity epidemic has been embraced by many scholars and researchers.

  10. Sulfated cholecystokinin-8 increases ghrelin secretion but does not affect oxyntomodulin in Holstein steers.

    Science.gov (United States)

    Yannaing, Swe; Thidarmyint, Hnin; Zhao, Hongqiong; Thanthan, Sint; Kitagawa, Kouki; Kuwayama, Hideto

    2012-08-01

    The effect of appetite regulatory hormone cholecystokinin (CCK) on the secretions of oxyntomodulin (OXM) and ghrelin, and the effect of ghrelin on the secretions of CCK and OXM were studied in ruminants. Eight Holstein steers, 7 months old, 243 ± 7 kg body weight (BW), were arranged in an incomplete Latin square design (8 animals × 4 treatments × 4 days of sampling). Steers were intravenously injected with 10 µg of sulfated CCK-8/kg BW, 20 µg of acyl ghrelin/kg BW, 100 µg of des-acyl ghrelin/kg BW or vehicle. Blood samples were collected from -60 min to 120 min relative to time of injection. Plasma concentrations of ghrelin, sulfated CCK and OXM were measured by double-antibody radioimmunoassay. Plasma acyl ghrelin was increased to peak level (428.3 ± 6 pg/mL) at 60 min after injection of CCK compared with pre-injected levels (203.3 ± 1 pg/mL). These results showed for the first time, that intravenous bolus injection of CCK increased ghrelin secretion in ruminants. In contrast, injection of ghrelin did not change CCK secretion. Administration of ghrelin or CCK has no effect on plasma OXM concentrations. In conclusion, our results show that administration of CCK increased ghrelin secretion but did not affect OXM release in ruminants. Ghrelin did not affect the secretions of CCK and OXM.

  11. 营养支持对近端胃次全切除术后血浆Ghrelin水平的影响%Effect of nutrition support on plasma ghrelin level after the proximal subtotal gastrectomy

    Institute of Scientific and Technical Information of China (English)

    王海涛; 卢麒丞; 王荣朝; 张云; 许军

    2011-01-01

    Objective To investigate the effect of nutrition support on plasma ghrelin level after the proximal subtotal gastrectomy. Methods Eighty-three patients with T1-3 N0-1 Mo gastric cancer underwent proximal subtotal gastrectomy were divided into two groups of A (enteral nutrition, 43 cases) and B(parenteral nutrition,40 cases). Plasma ghrelin levels were determined by RIA before and on the 1st ,3rd,5th,7th and 9th day after gastrectomy. Results Plasma ghrelin levels of two groups dropped to the nadir one day after gastrectomy, which were (33. 2±4. 2) % and (34.1±3. 7) % of the values before The recovery of plasma ghrelin levels on the 3rd day was greater in group A than that in group B[(47. 2+6. 2) % vs、 (38. 4±5. 7)%](P0. 05 ). Conclusion Compared to parenteral nutrition,enteral nutrition is better in promoting compensational secretion of ghrelin after proximal subtotal gastrectomy.%目的 研究营养支持对近端胃次全切除术后患者血浆ghrelin水平的影响.方法 选择83例行近端胃癌根治术的T1~3 N0~1M0胃癌患者,根据营养支持方式将患者分为肠内营养组(A组,43例)和肠外营养组(B组,40例).测定手术当天、术后第1、3、7、9天血浆ghrelin水平.结果 两组术后第1天血浆ghrlein水平下降至最低点,分别为术前的(33.2±4.2)%和(34.1±3.7)%.术后第3天,A组血浆ghrlein水平的回升快于B组[(47.2±6.2)% vs.(38.4±5.7)%](P<0.05);至术后第9天,两组的回升幅度才相仿,分别为术前的(70.4±5.9)%和(67.1±6.3)%(P>0.05).结论 肠内营养较肠外营养更能促进近端胃次全术后患者血浆ghrelin水平的恢复.

  12. Transgenic overexpression of intraislet ghrelin does not affect insulin secretion or glucose metabolism in vivo.

    Science.gov (United States)

    Bando, Mika; Iwakura, Hiroshi; Ariyasu, Hiroyuki; Hosoda, Hiroshi; Yamada, Go; Hosoda, Kiminori; Adachi, Souichi; Nakao, Kazuwa; Kangawa, Kenji; Akamizu, Takashi

    2012-02-15

    Whereas ghrelin is produced primarily in the stomach, a small amount of it is produced in pancreatic islets. Although exogenous administration of ghrelin suppresses insulin secretion in vitro or in vivo, the role of intraislet ghrelin in the regulation of insulin secretion in vivo remains unclear. To understand the physiological role of intraislet ghrelin in insulin secretion and glucose metabolism, we developed a transgenic (Tg) mouse model, rat insulin II promoter ghrelin-internal ribosomal entry site-ghrelin O-acyl transferase (RIP-GG) Tg mice, in which mouse ghrelin cDNA and ghrelin O-acyltransferase are overexpressed under the control of the rat insulin II promoter. Although pancreatic desacyl ghrelin levels were elevated in RIP-GG Tg mice, pancreatic ghrelin levels were not altered in animals on a standard diet. However, when Tg mice were fed a medium-chain triglyceride-rich diet (MCTD), pancreatic ghrelin levels were elevated to ∼16 times that seen in control animals. It seems likely that the gastric ghrelin cells possess specific machinery to provide the octanoyl acid necessary for ghrelin acylation but that this machinery is absent from pancreatic β-cells. Despite the overexpression of ghrelin, plasma ghrelin levels in the portal veins of RIP-GG Tg mice were unchanged from control levels. Glucose tolerance, insulin secretion, and islet architecture in RIP-GG Tg mice were not significantly different even when the mice were fed a MCTD. These results indicate that intraislet ghrelin does not play a major role in the regulation of insulin secretion in vivo.

  13. Reduced ghrelin secretion in the hypothalamus of rats due to cisplatin-induced anorexia.

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    Yakabi, Koji; Sadakane, Chiharu; Noguchi, Masamichi; Ohno, Shino; Ro, Shoki; Chinen, Katsuya; Aoyama, Toru; Sakurada, Tomoya; Takabayashi, Hideaki; Hattori, Tomohisa

    2010-08-01

    Although chemotherapy with cisplatin is a widely used and effective cancer treatment, the undesirable gastrointestinal side effects associated with it, such as nausea, vomiting, and anorexia, markedly decrease patients' quality of life. To elucidate the mechanism underlying chemotherapy-induced anorexia, focusing on the hypothalamic ghrelin secretion-anorexia association, we measured hypothalamic ghrelin secretion in fasted and cisplatin-treated rats. Hypothalamic ghrelin secretion changes after vagotomy or administration of cisplatin. Cisplatin + rikkunshito, a serotonin 2C receptor antagonist or serotonin 3 receptor antagonist, was investigated. The effects of intracerebroventricular (icv) administration of ghrelin or the serotonin 2C receptor antagonist SB242084 on food intake were also evaluated in cisplatin-treated rats. Hypothalamic ghrelin secretion significantly increased in 24-h-fasted rats compared to freely fed rats and was markedly reduced 24 and 48 h after cisplatin treatment in cisplatin-treated rats compared to saline-treated rats, although their plasma ghrelin levels were comparable. In cisplatin-treated rats, icv ghrelin administration reversed the decrease in food intake, vagotomy partially restored hypothalamic ghrelin secretion, and hypothalamic serotonin 2C receptor mRNA expression increased significantly. Administration of rikkunshito (an endogenous ghrelin enhancer) or a serotonin 2C receptor antagonist reversed the decrease in hypothalamic ghrelin secretion and food intake 24 h after cisplatin treatment. Cisplatin-induced anorexia is mediated through reduced hypothalamic ghrelin secretion. Cerebral serotonin 2C receptor activation partially induces decrease in hypothalamic ghrelin secretion, and rikkunshito suppresses cisplatin-induced anorexia by enhancing this secretion.

  14. Ghrelin and Metabolic Surgery

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    Dimitrios J. Pournaras

    2010-01-01

    Full Text Available Metabolic surgery is the most effective treatment for morbid obesity. Ghrelin has been implicated to play a role in the success of these procedures. Furthermore, these operations have been used to study the gut-brain axis. This article explores this interaction, reviewing the available data on changes in ghrelin levels after different surgical procedures.

  15. Ghrelin and cell differentiation

    Institute of Scientific and Technical Information of China (English)

    Geyang Xu; Yin Li; Wenjiao An; Weizhen Zhang

    2008-01-01

    Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is a gastric hormone that has been found to have a wide variety of biological functions. This review summarizes our current understanding of the effects of ghrelin on cell differentiation and tissue development, with an emphasis on the lineage determination of mesenchymal stem cells.

  16. 胰腺内分泌肿瘤ghrelin和受体GHS-R1A的表达及患者血浆ghrelin、瘦素水平%Expression of ghrelin and its receptor GHS-R 1A in pancreatic endocrine tumors and the plasma levels of ghrelin and leptin

    Institute of Scientific and Technical Information of China (English)

    吴海燕; 鲁重美; 陈原稼; 黎明; 刘丹; 肖雨; 朱丽明; 刘贝; 向红丁; 陈杰; 徐涛

    2010-01-01

    目的 检测胰腺内分泌肿瘤患者血浆及肿瘤组织ghrelin水平、血浆瘦素水平,探讨它们之间的关系及临床意义.方法 采用ELISA法检测11例胰腺内分泌肿瘤患者的术前血浆ghrelin及瘦素水平,以28例正常志愿者作为对照.免疫组织化学染色法检测11个肿瘤和27个对照组织ghrelin及其受体GHS-R1A的表达.并与临床病理资料进行相关分析.结果 胰腺内分泌肿瘤患者血浆ghrelin水平为(16.0±5.0)pg/ml,显著低于对照组的(21.0±2.0)pg/ml(P=0.047);瘦素水平为(0.34±0.03)ng/ml,与对照组的(0.38±0.04)ng/ml无显著差异.肿瘤患者的血浆ghrelin与瘦素水平呈正相关(P=0.015),但与各项临床病理指标均不相关;对照组的血浆瘦素水平与体重指数呈正相关(P=0.002),而肿瘤患者两者不相关.肿瘤组织ghrelin的表达率明显低于对照组织(64%对100%,P=0.004),而GHS-R1A的表达率与对照组无显著差异.肿瘤组织ghrelin和GHS-R 1A的表达与各项临床病理指标均不相关.结论 胰腺内分泌肿瘤表达ghrelin及GHS-R1A,患者血浆ghrelin及瘦素水平发生变化.%Objective To study the plasma and intratumoral levels of ghrelin, leptin and their relationship and clinical significance in patients with pancreatic endocrine tumor.Methods Preoperative plasma levels of ghrelin and leptin were detected by ELISA in 11 patients with pancreatic endocrine tumors and 28 normal controls.Expressions of ghrelin and its receptor GHS-R 1A were tested in 11 tumors and 27 paired control tissues by immunohistochemistry staining, and they were correlated with the clinicopathological characteristics.Results The plasma levels of ghrelin was ( 16.0 ± 5.0) pg/ml, which was significantly lower than that in normal controls [ (21.0 ± 2.0) pg/ml, P = 0.047 ].The plasma levels of leptin was (0.34 ±0.03 ) ng/ml, which was not significantly different with that in normal controls [ 0.38 ± 0.04) ng/ml ].There was positive association between

  17. Blunted hypothalamic ghrelin signaling reduces diet intake in rats fed a low-protein diet in late pregnancy.

    Science.gov (United States)

    Gao, Haijun; Sisley, Stephanie; Yallampalli, Chandra

    2015-12-01

    Diet intake in pregnant rats fed a low-protein (LP) diet was significantly reduced during late pregnancy despite elevated plasma levels of ghrelin. In this study, we hypothesized that ghrelin signaling in the hypothalamus is blunted under a low-protein diet condition and therefore, it does not stimulate diet intake during late pregnancy. Female Sprague-Dawley rats were fed a normal (CT) or LP diet from Day 1 of pregnancy. On Day 21, 0.5 μg ghrelin was given into the third ventricle (ICV). Diet and water intake at 30, 60, and 120 min after ICV injection was measured. Hypothalami were dissected and analyzed for expression of genes related to appetite regulation (Npy, Agrp, Pomc and Cart) and phosphorylation of AMPK and ACC proteins (downstream proteins of ghrelin receptor activation). Results include: In response to ICV injection of ghrelin, (1) diet intake was significantly lower in LP compared to CT rats; (2) water intake was not affected in LP rats; (3) expression of Npy and Agrp, but not Pomc and Cart, were higher in the hypothalamus of LP compared to CT rats; (4) the abundance of phosphorylated AMPK and the ratio of phosphorylated to total AMPK, but not the abundance of total AMPK, were lower in LP compared to CT rats; (5) the abundance of phosphorylated ACC, but not total ACC, was lower in LP rats. These findings suggest that blunted ghrelin signaling in the hypothalamus of pregnant rats fed a LP diet leads to reduced diet intake and exacerbates gestational protein insufficiency.

  18. Chronic Renal Failure, Cachexia, and Ghrelin

    Directory of Open Access Journals (Sweden)

    A. Laviano

    2010-01-01

    Full Text Available Protein energy wasting is frequently observed in patients with advanced chronic renal failure and end-stage renal disease. Anorexia and reduced food intake are critical contributing factors and negatively impact on patients' survival. Ghrelin is a prophagic peptide produced by the stomach and acting at the hypothalamic level to increase the activity of orexigenic neurons. In patients with chronic renal disease, plasma levels are increased as a likely effect of reduced renal clearance. Nevertheless, patients' food intake is significantly reduced, suggesting inflammation-mediated resistance of hypothalamic nuclei to peripheral signals. A number of forms of evidence show that ghrelin resistance could be overcome by the administration of exogenous ghrelin. Therefore, ghrelin has been proposed as a potential strategy to improve food intake in chronic renal failure patients with protein energy wasting. Preliminary data are encouraging although larger prospective clinical trials are needed to confirm the results and to identify those patients who are likely to benefit most from the administration of exogenous ghrelin.

  19. Chronic renal failure, cachexia, and ghrelin.

    Science.gov (United States)

    Laviano, A; Krznaric, Z; Sanchez-Lara, K; Preziosa, I; Cascino, A; Rossi Fanelli, F

    2010-01-01

    Protein energy wasting is frequently observed in patients with advanced chronic renal failure and end-stage renal disease. Anorexia and reduced food intake are critical contributing factors and negatively impact on patients' survival. Ghrelin is a prophagic peptide produced by the stomach and acting at the hypothalamic level to increase the activity of orexigenic neurons. In patients with chronic renal disease, plasma levels are increased as a likely effect of reduced renal clearance. Nevertheless, patients' food intake is significantly reduced, suggesting inflammation-mediated resistance of hypothalamic nuclei to peripheral signals. A number of forms of evidence show that ghrelin resistance could be overcome by the administration of exogenous ghrelin. Therefore, ghrelin has been proposed as a potential strategy to improve food intake in chronic renal failure patients with protein energy wasting. Preliminary data are encouraging although larger prospective clinical trials are needed to confirm the results and to identify those patients who are likely to benefit most from the administration of exogenous ghrelin.

  20. Effects of ghrelin on anorexia in tumor-bearing mice with eicosanoid-related cachexia.

    Science.gov (United States)

    Wang, Wenhua; Andersson, Marianne; Iresjö, Britt-Marie; Lönnroth, Christina; Lundholm, Kent

    2006-06-01

    Ghrelin is a novel brain-gut peptide that stimulates food intake and may secondarily increase body weight via a growth hormone secretagogue receptor (GHS-R). Tumor-bearing mice (MCG101), characterized by anorexia, fat loss and muscle wasting due to increased concentration of PGE2 and proinflammatory cytokines (IL-1beta, IL-6, TNF-alpha), were provided ghrelin i.p. at a low (20 microg/day) and high dose (40 microg/day) to examine the ability of ghrelin to counteract tumor-induced anorexia. Immunohistochemical staining and Western blot analyses were used to identify GHS-R expression in the brain as well as its relationship to NPY expression in hypothalamic neurons. GHS-R mRNA in hypothalamus and ghrelin mRNA in gastric fundus were quantified by RT-PCR. Body composition was determined by carcass extractions. GHS-R expression in hypothalamus and plasma ghrelin levels were significantly increased in freely-fed tumor-bearing mice, while gastric fundus expression of ghrelin was unaltered compared to non-tumor-bearing mice (controls). Ghrelin treatment increased food intake, body weight and whole body fat at both low and high doses of ghrelin in normal controls, while tumor-bearing mice showed improved intake and body composition at the high dose of ghrelin only. Exogenous ghrelin normalized the GHS-R expression in hypothalamus from tumor-bearing mice without alterations in the gastric fundus expression of ghrelin. Tumor growth was not altered by exogenous ghrelin. Our results indicate that MCG 101-bearing mice became ghrelin resistant despite upregulation of hypothalamic GHS-R expression, which confirms similar indirect observations in cancer patients. Thus, other factors downstream of the ghrelin-GHS-R system appear to be more important than ghrelin to explain cancer-induced anorexia.

  1. Altered lipid and salt taste responsivity in ghrelin and GOAT null mice.

    Directory of Open Access Journals (Sweden)

    Huan Cai

    Full Text Available Taste perception plays an important role in regulating food preference, eating behavior and energy homeostasis. Taste perception is modulated by a variety of factors, including gastric hormones such as ghrelin. Ghrelin can regulate growth hormone release, food intake, adiposity, and energy metabolism. Octanoylation of ghrelin by ghrelin O-acyltransferase (GOAT is a specific post-translational modification which is essential for many biological activities of ghrelin. Ghrelin and GOAT are both widely expressed in many organs including the gustatory system. In the current study, overall metabolic profiles were assessed in wild-type (WT, ghrelin knockout (ghrelin(-/-, and GOAT knockout (GOAT(-/- mice. Ghrelin(-/- mice exhibited decreased food intake, increased plasma triglycerides and increased ketone bodies compared to WT mice while demonstrating WT-like body weight, fat composition and glucose control. In contrast GOAT(-/- mice exhibited reduced body weight, adiposity, resting glucose and insulin levels compared to WT mice. Brief access taste behavioral tests were performed to determine taste responsivity in WT, ghrelin(-/- and GOAT(-/- mice. Ghrelin and GOAT null mice possessed reduced lipid taste responsivity. Furthermore, we found that salty taste responsivity was attenuated in ghrelin(-/- mice, yet potentiated in GOAT(-/- mice compared to WT mice. Expression of the potential lipid taste regulators Cd36 and Gpr120 were reduced in the taste buds of ghrelin and GOAT null mice, while the salt-sensitive ENaC subunit was increased in GOAT(-/- mice compared with WT mice. The altered expression of Cd36, Gpr120 and ENaC may be responsible for the altered lipid and salt taste perception in ghrelin(-/- and GOAT(-/- mice. The data presented in the current study potentially implicates ghrelin signaling activity in the modulation of both lipid and salt taste modalities.

  2. Altered lipid and salt taste responsivity in ghrelin and GOAT null mice.

    Science.gov (United States)

    Cai, Huan; Cong, Wei-Na; Daimon, Caitlin M; Wang, Rui; Tschöp, Matthias H; Sévigny, Jean; Martin, Bronwen; Maudsley, Stuart

    2013-01-01

    Taste perception plays an important role in regulating food preference, eating behavior and energy homeostasis. Taste perception is modulated by a variety of factors, including gastric hormones such as ghrelin. Ghrelin can regulate growth hormone release, food intake, adiposity, and energy metabolism. Octanoylation of ghrelin by ghrelin O-acyltransferase (GOAT) is a specific post-translational modification which is essential for many biological activities of ghrelin. Ghrelin and GOAT are both widely expressed in many organs including the gustatory system. In the current study, overall metabolic profiles were assessed in wild-type (WT), ghrelin knockout (ghrelin(-/-)), and GOAT knockout (GOAT(-/-)) mice. Ghrelin(-/-) mice exhibited decreased food intake, increased plasma triglycerides and increased ketone bodies compared to WT mice while demonstrating WT-like body weight, fat composition and glucose control. In contrast GOAT(-/-) mice exhibited reduced body weight, adiposity, resting glucose and insulin levels compared to WT mice. Brief access taste behavioral tests were performed to determine taste responsivity in WT, ghrelin(-/-) and GOAT(-/-) mice. Ghrelin and GOAT null mice possessed reduced lipid taste responsivity. Furthermore, we found that salty taste responsivity was attenuated in ghrelin(-/-) mice, yet potentiated in GOAT(-/-) mice compared to WT mice. Expression of the potential lipid taste regulators Cd36 and Gpr120 were reduced in the taste buds of ghrelin and GOAT null mice, while the salt-sensitive ENaC subunit was increased in GOAT(-/-) mice compared with WT mice. The altered expression of Cd36, Gpr120 and ENaC may be responsible for the altered lipid and salt taste perception in ghrelin(-/-) and GOAT(-/-) mice. The data presented in the current study potentially implicates ghrelin signaling activity in the modulation of both lipid and salt taste modalities.

  3. Spectrophotometric and Refractometric Determination of Total Protein in Avian Plasma

    Directory of Open Access Journals (Sweden)

    Rodica Căpriță

    2013-10-01

    Full Text Available The aim of this study was to compare the total protein values obtained in heparin plasma of chickens by a spectrophotometric technique (biuret method, and the values obtained on the same day in the same samples by refractometry. The results obtained by refractometry (average value 2.638±0.153g% were higher than those obtained by the spectrophotometric method (average value 2.441±0.181g%. There was a low correlation (r = 0.6709 between the total protein values, determined with both methods. Protein is the major determinant of plasma refractive index, but glucose contributes too. The refractometric method is not recommended in chickens for the determination of total protein, because avian blood glucose concentration averages about twice than in mammalian blood.

  4. Stress increased ghrelin secretion from pancreatic isolated islets in male rats.

    Science.gov (United States)

    Rostamkhani, Fatemeh; Zardooz, Homeira; Goshadrou, Fatemeh; Baveisi, Mahyar; Hedayati, Mehdi

    2016-01-01

    It has been demonstrated that plasma ghrelin is likely affected by stress, but little attention has been paid to the effect of stress on ghrelin release from pancreatic islets. This study investigates the effect of stress on ghrelin secretion from pancreatic islets in rats. Male Wistar rats were divided into control and stressed groups. The stressed group was further divided into foot-shock and psychological stress subgroups. Stress was induced by a communication box. After stress exposure, blood sampling was performed to determine the plasma levels of corticosterone, glucose, and ghrelin. Then the animals' pancreatic islets were isolated to assess their ghrelin output at 5.6, 8.3, and 16.7 mM glucose concentrations. Acute exposure to foot-shock and psychological stress both increased plasma corticosterone concentration. Moreover, plasma glucose concentration increased in the foot-shock stress group. Chronic exposure to foot-shock decreased plasma ghrelin concentration, whereas acute exposure had no significant effect. Acute and chronic exposure to foot-shock and psychological stress increased ghrelin secretion from isolated islets in the presence of different glucose concentrations. The results of the present study suggest that ghrelin secretion from isolated islets is not glucose-dependent. However, ghrelin secretion appears to be intensely responsive to both acute and chronic stress.

  5. Novel regulator of acylated ghrelin, CF801, reduces weight gain, rebound feeding after a fast, and adiposity in mice

    Directory of Open Access Journals (Sweden)

    Martin K Wellman

    2015-09-01

    Full Text Available Ghrelin is a 28 amino-acid hormonal peptide that is intimately related to the regulation of food intake and body weight. Once secreted, ghrelin binds to the growth hormone secretagogue receptor-1a (GHSR-1a, the only known receptor for ghrelin and is capable of activating a number of signaling cascades ultimately resulting in an increase in food intake and adiposity. Because ghrelin has been linked to overeating and the development of obesity, a number of pharmacological interventions have been generated in order to interfere with either the activation of ghrelin or interrupting ghrelin signaling as a means to reducing appetite and decrease weight gain. Here we present a novel peptide, CF801, capable of reducing circulating acylated ghrelin levels and subsequent body weight gain and adiposity. To this end, we show that IP administration of CF801 is sufficient to reduce circulating plasma acylated ghrelin levels. Acutely, intraperitoneal injections of CF801 resulted in decreased rebound feeding after an overnight fast. When delivered chronically decreased weight gain and adiposity without affecting caloric intake. CF801, however, did cause a change in diet preference, decreasing preference for a high fat diet and increasing preference for regular chow diet. Given the complexity of ghrelin receptor function, we propose that CF801 along with other compounds that regulate ghrelin secretion may prove to be a beneficial tool in the study of the ghrelin system, and potential targets for ghrelin based obesity treatments without altering the function of ghrelin receptors.

  6. The ghrelin axis--does it have an appetite for cancer progression?

    Science.gov (United States)

    Chopin, Lisa K; Seim, Inge; Walpole, Carina M; Herington, Adrian C

    2012-12-01

    Ghrelin, the endogenous ligand for the GH secretagogue receptor (GHSR), is a peptide hormone with diverse physiological roles. Ghrelin regulates GH release, appetite and feeding, gut motility, and energy balance and also has roles in the cardiovascular, immune, and reproductive systems. Ghrelin and the GHSR are expressed in a wide range of normal and tumor tissues, and a fluorescein-labeled, truncated form of ghrelin is showing promise as a biomarker for prostate cancer. Plasma ghrelin levels are generally inversely related to body mass index and are unlikely to be useful as a biomarker for cancer, but may be useful as a marker for cancer cachexia. Some single nucleotide polymorphisms in the ghrelin and GHSR genes have shown associations with cancer risk; however, larger studies are required. Ghrelin regulates processes associated with cancer, including cell proliferation, apoptosis, cell migration, cell invasion, inflammation, and angiogenesis; however, the role of ghrelin in cancer is currently unclear. Ghrelin has predominantly antiinflammatory effects and may play a role in protecting against cancer-related inflammation. Ghrelin and its analogs show promise as treatments for cancer-related cachexia. Further studies using in vivo models are required to determine whether ghrelin has a role in cancer progression.

  7. Ghrelin and cancer.

    Science.gov (United States)

    Chopin, Lisa; Walpole, Carina; Seim, Inge; Cunningham, Peter; Murray, Rachael; Whiteside, Eliza; Josh, Peter; Herington, Adrian

    2011-06-20

    Ghrelin is a peptide hormone that was originally isolated from the stomach as the endogenous ligand for the growth hormone secretagogue receptor (GHSR). Ghrelin has many functions, including the regulation of appetite and gut motility, growth hormone release from the anterior pituitary and roles in the cardiovascular and immune systems. Ghrelin and its receptor are expressed in a number of cancers and cancer cell lines and may play a role in processes associated with cancer progression, including cell proliferation, apoptosis, and cell invasion and migration.

  8. [Leptin, ghrelin, and physical exercise].

    Science.gov (United States)

    da Mota, Gustavo R; Zanesco, Angelina

    2007-02-01

    Obesity is a major public health problem in the Western world resulting in serious social, physical and psychological damages. The genesis of obesity is complex involving a variety of factors such as genetic, psychological, metabolic and environmental factors. Progress in endocrinology and metabolism show that adipocyte is considered now as an endocrine tissue producing several substance including adiponectin, tumor necrosis factor-alpha, interleukin-6 and leptin. Specifically, leptin is the main peptide produced by the adipocyte and its serum concentration represents an important peripheral signal in the regulation of food intake and energy expenditure in mammals. In addition to leptin, a new peptide was discovered recently named ghrelin. Ghrelin, a peptide hormone identified in the stomach, is directly involved with the regulation of energy balance and obesity. Physical exercise has been used as a non-pharmacological tool in management of body weight and the effect of physical activity on weight control is an important issue for clinical studies in endocrinology field. Thus, this review will attempt to update the knowledge of leptin and ghrelin on the body weight regulation and the effect of exercise training on these peptide concentrations. It can be concluded that the relationship between physical exercise and the plasma concentration of these peptides is not clear. The reasons for that could be related to the differences in duration, intensity and frequency of the training program employed in each study. Indeed, most of the studies have not analyzed the intensity of training program by either plasma lactate concentration or maximum oxygen consumption. On the other hand, genetic basis could also explain the discrepancies found in some studies, since it has been shown that polymorphism for a variety of genes might be an important factor to determine the differences of cellular response to physical training.

  9. Ghrelin-Reactive Immunoglobulins in Conditions of Altered Appetite and Energy Balance

    Science.gov (United States)

    Fetissov, Sergueï O.; Lucas, Nicolas; Legrand, Romain

    2017-01-01

    Part of circulating ghrelin is bound to immunoglobulins (Ig) protecting it from degradation and preserving its functional activity. This review summarizes the data on ghrelin- and desacyl-ghrelin-reactive IgG in conditions of altered appetite and energy balance. Plasma levels and affinity kinetics of such IgG were compared in patients with obesity and anorexia nervosa (AN) and in animal models of obesity including ob/ob mice, high-fat diet-induced obese mice, and obese Zucker rats as well as in mice after chronic food restriction and activity-based anorexia and in rats with methotrexate-induced anorexia. We show that plasmatic IgG in both obese humans and animals are characterized by increased affinity for ghrelin. In contrast, patients with AN and anorectic rodents all show lower affinity of ghrelin- and desacyl-ghrelin-reactive IgG, respectively, the changes which were not observed in non-anorectic, chronically starved mice. We also show that affinity of ghrelin-reactive IgG correlate with plasma levels of ghrelin. These data point to common mechanisms underlying modifications of affinity kinetics properties of ghrelin-reactive IgG during chronic alterations of energy balance in humans and rodents and support a functional role of such autoantibodies in ghrelin-mediated regulation of appetite. PMID:28191004

  10. Spectrophotometric and Refractometric Determination of Total Protein in Avian Plasma

    OpenAIRE

    2013-01-01

    The aim of this study was to compare the total protein values obtained in heparin plasma of chickens by a spectrophotometric technique (biuret method), and the values obtained on the same day in the same samples by refractometry. The results obtained by refractometry (average value 2.638±0.153g%) were higher than those obtained by the spectrophotometric method (average value 2.441±0.181g%). There was a low correlation (r = 0.6709) between the total protein values, determined with both methods...

  11. Molecular evolution of GPCRs: Ghrelin/ghrelin receptors.

    Science.gov (United States)

    Kaiya, Hiroyuki; Kangawa, Kenji; Miyazato, Mikiya

    2014-06-01

    After the discovery in 1996 of the GH secretagogue-receptor type-1a (GHS-R1a) as an orphan G-protein coupled receptor, many research groups attempted to identify the endogenous ligand. Finally, Kojima and colleagues successfully isolated the peptide ligand from rat stomach extracts, determined its structure, and named it ghrelin. The GHS-R1a is now accepted to be the ghrelin receptor. The existence of the ghrelin system has been demonstrated in many animal classes through biochemical and molecular biological strategies as well as through genome projects. Our work, focused on identifying the ghrelin receptor and its ligand ghrelin in laboratory animals, particularly nonmammalian vertebrates, has provided new insights into the molecular evolution of the ghrelin receptor. In mammals, it is assumed that the ghrelin receptor evolution is in line with the plate tectonics theory. In contrast, the evolution of the ghrelin receptor in nonmammalian vertebrates differs from that of mammals: multiplicity of the ghrelin receptor isoforms is observed in nonmammalian vertebrates only. This multiplicity is due to genome duplication and polyploidization events that particularly occurred in Teleostei. Furthermore, it is likely that the evolution of the ghrelin receptor is distinct from that of its ligand, ghrelin, because only one ghrelin isoform has been detected in all species examined so far. In this review, we summarize current knowledge related to the molecular evolution of the ghrelin receptor in mammalian and nonmammalian vertebrates. © 2014 Society for Endocrinology.

  12. Plasma Total Cysteine and Cardiovascular Risk Burden: Action and Interaction

    Directory of Open Access Journals (Sweden)

    Benedetta De Chiara

    2012-01-01

    Full Text Available We hypothesized that redox analysis could provide sensitive markers of the oxidative pathway associated to the presence of an increasing number of cardiovascular risk factors (RFs, independently of type. We classified 304 subjects without cardiovascular disease into 4 groups according to the total number of RFs (smoking, hypertension, hypercholesterolaemia, hyperhomocysteinaemia, diabetes, obesity, and their combination. Oxidative stress was evaluated by measuring plasma total and reduced homocysteine, cysteine (Cys, glutathione, cysteinylglycine, blood reduced glutathione, and malondialdehyde. Twenty-seven percent of subjects were in group 0 RF, 26% in 1 RF, 31% in 2 RF, and 16% in ≥3 RF. By multivariable ordinal regression analysis, plasma total Cys was associated to a higher number of RF (OR = 1.068; 95% CI = 1.027–1.110, =0.002. Total RF burden is associated with increased total Cys levels. These findings support a prooxidant effect of Cys in conjunction with RF burden, and shed light on the pathophysiologic role of redox state unbalance in preclinical atherosclerosis.

  13. Postprandial inhibition of gastric ghrelin secretion by long-chain fatty acid through GPR120 in isolated gastric ghrelin cells and mice.

    Science.gov (United States)

    Lu, Xinping; Zhao, Xilin; Feng, Jianying; Liou, Alice P; Anthony, Shari; Pechhold, Susanne; Sun, Yuxiang; Lu, Huiyan; Wank, Stephen

    2012-08-01

    Ghrelin is a gastric peptide hormone that controls appetite and energy homeostasis. Plasma ghrelin levels rise before a meal and fall quickly thereafter. Elucidation of the regulation of ghrelin secretion has been hampered by the difficulty of directly interrogating ghrelin cells diffusely scattered within the complex gastric mucosa. Therefore, we generated transgenic mice with ghrelin cell expression of green fluorescent protein (GFP) to enable characterization of ghrelin secretion in a pure population of isolated gastric ghrelin-expressing GFP (Ghr-GFP) cells. Using quantitative RT-PCR and immunofluorescence staining, we detected a high level of expression of the long-chain fatty acid (LCFA) receptor GPR120, while the other LCFA receptor, GPR40, was undetectable. In short-term-cultured pure Ghr-GFP cells, the LCFAs docosadienoic acid, linolenic acid, and palmitoleic acid significantly suppressed ghrelin secretion. The physiological mechanism of LCFA inhibition on ghrelin secretion was studied in mice. Serum ghrelin levels were transiently suppressed after gastric gavage of LCFA-rich lipid in mice with pylorus ligation, indicating that the ghrelin cell may directly sense increased gastric LCFA derived from ingested intraluminal lipids. Meal-induced increase in gastric mucosal LCFA was assessed by measuring the transcripts of markers for tissue uptake of LCFA, lipoprotein lipase (LPL), fatty acid translocase (CD36), glycosylphosphatidylinositol-anchored HDL-binding protein 1, and nuclear fatty acid receptor peroxisome proliferator-activated receptor-γ. Quantitative RT-PCR studies indicate significantly increased mRNA levels of lipoprotein lipase, glycosylphosphatidylinositol-anchored HDL-binding protein 1, and peroxisome proliferator-activated receptor-γ in postprandial gastric mucosa. These results suggest that meal-related increases in gastric mucosal LCFA interact with GPR120 on ghrelin cells to inhibit ghrelin secretion.

  14. Ghrelin and eating disorders

    National Research Council Canada - National Science Library

    Fabbri, Alessandra Donzelli; Deram, Sophie; Kerr, Daniel Shikanai; Cordás, Táki Athanássios

    2015-01-01

    ...; we searched PubMed, Scientific Electronic Library Online (SciELO), and LILACS databases using the keywords "eating disorder", "ghrelin", "polymorphism", "anorexia nervosa", "bulimia nervosa", "binge eating disorder", and their combinations...

  15. Low plasma carnitine in patients on prolonged total parenteral nutrition: association with low plasma lysine.

    Science.gov (United States)

    Berner, Y N; Larchian, W A; Lowry, S F; Nicroa, R R; Brennan, M F; Shike, M

    1990-01-01

    Plasma carnitine levels were determined in 17 patients maintained on long-term total parenteral nutrition (TPN) for a mean (+/- SEM) period of 69 +/- 11 months (range 12-196). All had severe malabsorption and were dependent on intravenous feeding. Plasma carnitine was determined by a modified Cederblad enzymatic method. Mean plasma carnitine was significantly below the mean normal for females (p less than 0.02) and borderline low for males (p = 0.07). In six patients the levels were below the low normal range, and in five others they were at the lowest levels of normal. Of the six patients with normal levels, three had elevated serum creatinine, indicating renal dysfunction which may by itself elevate plasma carnitine. In 10 patients the plasma levels of lysine (a carnitine precursor) were determined and found to be lower than normal (p less than 0.05). Plasma carnitine levels correlated positively with serum albumin (r = 0.62, p less than 0.05), and negatively with serum alkaline phosphatase (r = -0.64, p less than 0.05). Thus, patients maintained on long-term TPN may have low plasma carnitine, which could represent carnitine deficiency. The low plasma carnitine may be related to a deficiency of the carnitine precursor lysine. Further studies are required to determine the significance of the low plasma carnitine and whether carnitine supplementation should be required in long-term TPN.

  16. Acipimox during exercise points to an inhibitory feedback of GH on ghrelin secretion in bulimic and healthy women.

    Science.gov (United States)

    Nedvidkova, Jara; Smitka, Kvido; Papezova, Hana; Vondra, Karel; Hill, Martin; Hainer, Vojtech

    2011-02-25

    Ghrelin is predominantly produced by the stomach and the growth hormone (GH)-ghrelin feedback loop between the stomach and the pituitary gland has recently been suggested. The disruption of the gut-brain axis might be involved in bulimia nervosa (BN). We investigated responses of plasma GH, ghrelin, and neuropeptide Y (NPY) concentrations to exercise or to exercise after the administration of the antilipolytic drug Acipimox (Aci) in seven BN patients and seven healthy women (C). Aci was administered 1h before exercise (45 min, 2 W/kg of lean body mass/LBM/). Ghrelin, GH, NPY, free fatty acids (FFA) and glycerol plasma levels were measured during the test using commercial kits. The exercise induced an increase in plasma GH, NPY and FFA in both groups and a decrease in plasma ghrelin levels only in BN patients. Exercise after Aci administration resulted in an increase in plasma GH, and a decrease in plasma ghrelin in both groups; NPY increased more in BN patients. Exercise-induced FFA increase was depressed after Aci. We conclude that the Aci-induced suppression in plasma ghrelin levels during exercise in both groups suggests a negative feedback of GH on ghrelin secretion. Observed changes in plasma FFA levels were not related to changes in GH and ghrelin levels. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. [Ghrelin: beyond hunger regulation].

    Science.gov (United States)

    Milke García, Maria del Pilar

    2005-01-01

    Man ingests food to mitigate hunger (mediated by physiological and biochemical signals), satisfy appetite (subjective sensation) and because of psychosocial reasons. Satiation biomarkers (stop feeding) are gastric distention and hormones (CCK, GLP-1) and satiety biomarkers (induce feeding) are food-induced thermogenesis, body temperature, glycaemia and also hormones (insulin, leptin and ghrelin). Oxidative metabolism/body composition, tryptophan/serotonin and proinflammatory cytokines are also implicated on hunger physiology. At the present time, ghrelin is the only known circulating orexigenic with potential on hunger/body weight regulation. It is a neuropeptide (endogenous ligand for the GH secretagogue) recently isolated from the oxyntic mucosa and synthesized mainly in the stomach. Its blood concentration depends on diet, hyperglucemia and adiposity/leptin. It is secreted 1-2 hours preprandially and its concentration decreases drastically during the postprandium. Ghrelin acts on the lateral hypothalamus and theoretically inhibits proinflammatory cytokine secretion and antagonizes leptin. Ghrelin physiologically increases food intake and stimulates adipogenesis, gastrointestinal motility and gastric acid secretion, and has other hormonal and cardiovascular functions. Ghrelin blood concentration is reduced in massive obesity, non-alcoholic steatohepatitis, polycystic ovary syndrome, acromegaly, hypogonadism, ageing, short bowel syndrome and rheumatoid arthritis; and increased in primary or secondary anorexia, starvation, chronic liver disease and celiac disease. Cerebral and peritoneal ghrelin administration (rats) and systemic administration (rats and healthy volunteers, cancer patients or patients on peritoneal dialysis) promotes food consumption and increases adiposity, of utmost importance in the treatment of patients with anorexia.

  18. Effect of ghrelin on glucose regulation in mice.

    Science.gov (United States)

    Chacko, Shaji K; Haymond, Morey W; Sun, Yuxiang; Marini, Juan C; Sauer, Pieter J J; Ma, Xiaojun; Sunehag, Agneta L

    2012-05-15

    Improvement of glucose metabolism after bariatric surgery appears to be from the composite effect of the alterations in multiple circulating gut hormone concentrations. However, their individual effect on glucose metabolism during different conditions is not clear. The objective of this study was to determine whether ghrelin has an impact on glycogenolysis, gluconeogenesis, and insulin sensitivity (using a mice model). Rate of appearance of glucose, glycogenolysis, and gluconeogenesis were measured in wild-type (WT), ghrelin knockout (ghrelin(-/-)), and growth hormone secretagogue receptor knockout (Ghsr(-/-)) mice in the postabsorptive state. The physiological nature of the fasting condition was ascertained by a short-term fast commenced immediately at the end of the dark cycle. Concentrations of glucose and insulin were measured, and insulin resistance and hepatic insulin sensitivity were calculated. Glucose concentrations were not different among the groups during the food-deprived period. However, plasma insulin concentrations were lower in the ghrelin(-/-) and Ghsr(-/-) than WT mice. The rates of gluconeogenesis, glycogenolysis, and indexes of insulin sensitivity were higher in the ghrelin(-/-) and Ghsr(-/-) than WT mice during the postabsorptive state. Insulin receptor substrate 1 and glucose transporter 2 gene expressions in hepatic tissues of the ghrelin(-/-) and Ghsr(-/-) were higher compared with that in WT mice. This study demonstrates that gluconeogenesis and glycogenolysis are increased and insulin sensitivity is improved by the ablation of the ghrelin or growth hormone secretagogue receptor in mice.

  19. Assay of ghrelin concentration in infant formulas and breast milk

    Institute of Scientific and Technical Information of China (English)

    Francesco Savino; Elisa Petrucci; Maria Maddalena Lupica; Giuliana Eva Nanni; Roberto Oggero

    2011-01-01

    AIM: To test if total ghrelin is present in infant formulas. METHODS: Using a radioimmunoassay, we measured total ghrelin concentrations in 19 samples of commercial infant formulas and in 20 samples of human milk. We also determined ghrelin concentration in the serum of infants and lactating mothers. RESULTS: Ghrelin concentrations were significantly higher in artificial milk (2007.1 ± 1725.36 pg/mL) than in human milk (828.17 ± 323.32 pg/mL) (P = 0.005). The mean ghrelin concentration in infant serum (n = 56) was 1115.86 ± 42.89 pg/mL, and was significantly higher (P = 0.023) in formula-fed infants (1247.93 ± 328.07 pg/mL) than in breast-fed infants (1045.7 ± 263.38 pg/mL). The mean serum ghrelin concentration (mean ± SD) in lactating mothers (n = 20) was 1319.18 ± 140.18 pg/mL. CONCLUSION: This study provides evidence that total ghrelin is present in infant formulas. This finding raises diverse questions regarding the uptake, absorp-tion and metabolic effects of this hormone.

  20. Ghrelin counteracts insulin-induced activation of vagal afferent neurons via growth hormone secretagogue receptor.

    Science.gov (United States)

    Iwasaki, Yusaku; Dezaki, Katsuya; Kumari, Parmila; Kakei, Masafumi; Yada, Toshihiko

    2015-08-01

    Vagal afferent nerves sense meal-related gastrointestinal and pancreatic hormones and convey their information to the brain, thereby regulating brain functions including feeding. We have recently demonstrated that postprandial insulin directly acts on the vagal afferent neurons. Plasma concentrations of orexigenic ghrelin and anorexigenic insulin show reciprocal dynamics before and after meals. The present study examined interactive effects of ghrelin and insulin on vagal afferent nerves. Cytosolic Ca(2+) concentration ([Ca(2+)]i) in isolated nodose ganglion (NG) neurons was measured to monitor their activity. Insulin at 10(-7)M increased [Ca(2+)]i in NG neurons, and the insulin-induced [Ca(2+)]i increase was inhibited by treatment with ghrelin at 10(-8)M. This inhibitory effect of ghrelin was attenuated by [D-Lys(3)]-GHRP-6, an antagonist of growth hormone-secretagogue receptor (GHSR). Des-acyl ghrelin had little effect on insulin-induced [Ca(2+)]i increases in NG neurons. Ghrelin did not affect [Ca(2+)]i increases in response to cholecystokinin (CCK), a hormone that inhibits feeding via vagal afferent neurons, indicating that ghrelin selectively counteracts the insulin action. These results demonstrate that ghrelin via GHSR suppresses insulin-induced activation of NG neurons. The action of ghrelin to counteract insulin effects on NG might serve to efficiently inform the brain of the systemic change between fasting-associated ghrelin-dominant and fed-associated insulin-dominant states for the homeostatic central regulation of feeding and metabolism.

  1. Excessive sympathoactivation and deteriorated heart function after myocardial infarction in male ghrelin knockout mice.

    Science.gov (United States)

    Mao, Yuanjie; Tokudome, Takeshi; Otani, Kentaro; Kishimoto, Ichiro; Miyazato, Mikiya; Kangawa, Kenji

    2013-05-01

    We have previously demonstrated the protective role of endogenous ghrelin against malignant arrhythmias in the very acute phase of myocardial infarction (MI). However, the role of endogenous ghrelin in the chronic phase is unknown. Therefore, the aim of the current study was to focus on the effects of endogenous ghrelin on cardiac function and sympathetic activation after acute MI. In 46 ghrelin-knockout (KO) and 41 wild-type (WT) male mice, MI was produced by left coronary artery ligation. The mortality due to heart failure within 2 weeks was 0% in WT and 10.9% in KO (P Metoprolol treatment and ghrelin treatment in KO mice prevented excessive sympathetic activation, decreased plasma epinephrine and norepinephrine levels, and improved heart function and survival rate after MI. Our data demonstrate that endogenous ghrelin plays a crucial role in protecting heart function and reducing mortality after myocardial infarction, and that these effects seem to be partly the result of sympathetic inhibition.

  2. Ghrelin and gastric acid secretion

    Institute of Scientific and Technical Information of China (English)

    Koji Yakabi; Junichi Kawashima; Shingo Kato

    2008-01-01

    Ghrelin, a novel growth hormone-releasing peptide, was originally isolated from rat and human stomach. Ghrelin has been known to increase the secretion of growth hormone (GH), food intake, and body weight gain when administered peripherally or centrally. Ghrelin is also known to stimulate the gastric motility and the secretion of gastric acid. In the previous studies, the action of ghrelin on acid secretion was shown to be as strong as that of histamine and gastrin in-vivo experiment. In the studies, the mechanism for the action of ghrelin was also investigated. It was shown that vagotomy completely inhibited the action of ghrelin on the secretion of gastric acid suggesting that vagal nerve is involved in the mechanism for the action of ghrelin on acid secretion. As famotidine did not inhibit ghrelin-in-duced acid secretion in the study by Masuda et al, they concluded that histamine was not involved in the action of ghrelin on acid secretion. However, we have shown that famotidine completely inhibited ghrelin-induced acid secretion and histidine decarboxylase (HDC) mRNA was increased in gastric mucosa by ghrelin injection which is inhibited by vagotomy Our results indicate that histamine is involved in the action of ghrelin on acid secretion. Furthermore synergistic action of gastrin and ghrelin on gastric add secretion was shown. Although gastrin has important roles in postprandial secretion of gastric acid, ghrelin may be related to acid secretion during fasting period or at night. However, further studies are needed to elucidate the physiological role of ghrelin in acid secretion.

  3. Ghrelin and gastric acid secretion.

    Science.gov (United States)

    Yakabi, Koji; Kawashima, Junichi; Kato, Shingo

    2008-11-07

    Ghrelin, a novel growth hormone-releasing peptide, was originally isolated from rat and human stomach. Ghrelin has been known to increase the secretion of growth hormone (GH), food intake, and body weight gain when administered peripherally or centrally. Ghrelin is also known to stimulate the gastric motility and the secretion of gastric acid. In the previous studies, the action of ghrelin on acid secretion was shown to be as strong as that of histamine and gastrin in in-vivo experiment. In the studies, the mechanism for the action of ghrelin was also investigated. It was shown that vagotomy completely inhibited the action of ghrelin on the secretion of gastric acid suggesting that vagal nerve is involved in the mechanism for the action of ghrelin on acid secretion. As famotidine did not inhibit ghrelin-induced acid secretion in the study by Masuda et al, they concluded that histamine was not involved in the action of ghrelin on acid secretion. However, we have shown that famotidine completely inhibited ghrelin-induced acid secretion and histidine decarboxylase (HDC) mRNA was increased in gastric mucosa by ghrelin injection which is inhibited by vagotomy Our results indicate that histamine is involved in the action of ghrelin on acid secretion. Furthermore synergistic action of gastrin and ghrelin on gastric acid secretion was shown. Although gastrin has important roles in postprandial secretion of gastric acid, ghrelin may be related to acid secretion during fasting period or at night. However, further studies are needed to elucidate the physiological role of ghrelin in acid secretion.

  4. Ghrelin and eating disorders

    Directory of Open Access Journals (Sweden)

    Alessandra Donzelli Fabbri

    2015-04-01

    Full Text Available Background Ghrelin is a potent hormone with central and peripheral action. This hormone plays an important role in the regulation of appetite, food intake, and energy balance. Studies have suggested that ghrelin is involved with eating disorders (ED, particularly bingeing and purging. Genetic variants have also been studied to explain changes in eating behavior. Methods We conducted a literature review; we searched PubMed, Scientific Electronic Library Online (SciELO, and LILACS databases using the keywords “eating disorder”, “ghrelin”, “polymorphism”, “anorexia nervosa”, “bulimia nervosa”, “binge eating disorder”, and their combinations. We found 319 articles. Thirty-nine articles met the inclusion criteria. Results High levels of ghrelin were found in patients with anorexia nervosa (AN, especially in the purging subtype (AN-P. There was also a positive correlation between fasting ghrelin level and frequency of episodes of bingeing/purging in bulimia nervosa (BN and the frequency of bingeing in periodic binge eating disorder (BED. Some polymorphisms were associated with AN and BN. Conclusion Changes in ghrelin levels and its polymorphism may be involved in the pathogenesis of EDs; however, further studies should be conducted to clarify the associations.

  5. Chronic Renal Failure, Cachexia, and Ghrelin

    OpenAIRE

    Laviano, A.; Krznaric, Z.; Sanchez-Lara, K.; Preziosa, I.; Cascino, A; Rossi Fanelli, F.

    2010-01-01

    Protein energy wasting is frequently observed in patients with advanced chronic renal failure and end-stage renal disease. Anorexia and reduced food intake are critical contributing factors and negatively impact on patients' survival. Ghrelin is a prophagic peptide produced by the stomach and acting at the hypothalamic level to increase the activity of orexigenic neurons. In patients with chronic renal disease, plasma levels are increased as a likely effect of reduced renal clearance. Neverth...

  6. Exercise and ghrelin. A narrative overview of research.

    Science.gov (United States)

    King, James A; Wasse, Lucy K; Stensel, David J; Nimmo, Myra A

    2013-09-01

    Since its discovery in 1999, ghrelin has been implicated in a multiplicity of physiological activities. Most notably, ghrelin has an important influence on energy metabolism and after the identification of its potent appetite stimulating effects ghrelin has been termed the 'hunger hormone'. Exercise is a stimulus which has a significant impact on energy homeostasis and consequently a substantial body of research has investigated the interaction between exercise and ghrelin. This narrative review provides an overview of research relating to the acute and chronic effects of exercise on circulating ghrelin (acylated, unacylated and total). To enhance study comparability, the scope of this review is limited to research undertaken in adult humans and consequently studies involving children and animals are not discussed. Although there is significant ambiguity within much of the early research, our review suggests that acute exercise transiently interferes with the production of acylated ghrelin. Furthermore, the consensus of evidence indicates that exercise training does not influence circulating ghrelin independent of weight loss. Additional research is needed to verify and extend the available literature, particularly by uncovering the mechanisms governing acute exercise-related changes and characterising responses in other populations such as females, older adults, and the obese.

  7. Changes in Plasma Lipids during Exposure to Total Sleep Deprivation.

    Science.gov (United States)

    Chua, Eric Chern-Pin; Shui, Guanghou; Cazenave-Gassiot, Amaury; Wenk, Markus R; Gooley, Joshua J

    2015-11-01

    The effects of sleep loss on plasma lipids, which play an important role in energy homeostasis and signaling, have not been systematically examined. Our aim was to identify lipid species in plasma that increase or decrease reliably during exposure to total sleep deprivation. Twenty individuals underwent sleep deprivation in a laboratory setting. Blood was drawn every 4 h and mass spectrometry techniques were used to analyze concentrations of 263 lipid species in plasma, including glycerolipids, glycerophospholipids, sphingolipids, and sterols. Chronobiology and Sleep Laboratory, Duke-NUS Graduate Medical School. Healthy ethnic-Chinese males aged 21-28 y (n = 20). Subjects were kept awake for 40 consecutive hours. Each metabolite time series was modeled as a sum of sinusoidal (circadian) and linear components, and we assessed whether the slope of the linear component differed from zero. More than a third of all individually analyzed lipid profiles exhibited a circadian rhythm and/or a linear change in concentration during sleep deprivation. Twenty-five lipid species showed a linear and predominantly unidirectional trend in concentration levels that was consistent across participants. Choline plasmalogen levels decreased, whereas several phosphatidylcholine (PC) species and triacylglycerides (TAG) carrying polyunsaturated fatty acids increased. The decrease in choline plasmalogen levels during sleep deprivation is consistent with prior work demonstrating that these lipids are susceptible to degradation by oxidative stress. The increase in phosphatidylcholines and triacylglycerides suggests that sleep loss might modulate lipid metabolism, which has potential implications for metabolic health in individuals who do not achieve adequate sleep. © 2015 Associated Professional Sleep Societies, LLC.

  8. Ghrelin in the human myometrium

    LENUS (Irish Health Repository)

    O'Brien, Margaret

    2010-05-28

    Abstract Background Ghrelin is a 28-amino acid octanolyated peptide, synthesised primarily in the stomach. It stimulates growth hormone release, food intake and exhibits many other diverse effects. Our group have previously determined that ghrelin inhibited human contractility in vitro. The aim of this study therefore, was to investigate the expression of ghrelin, its receptor, the growth hormone secretagogue receptor type 1 (GHS-R1), ghrelin O-acyltransferase (GOAT) which catalyses ghrelin octanoylation, prohormone convertase 1\\/3 (PC1\\/3) responsible for pro-ghrelin processing, in human myometrium, during pregnancy prior to labour, during labour and in the non-pregnant state. Modulation of ghrelin and ghrelin receptor expression in cultured myometrial cells was also investigated. Methods mRNA and protein were isolated from human myometrium and the myometrial smooth muscle cell line hTERT-HM; and real-time fluorescence RT-PCR, western blotting and fluorescence microscopy performed. The effects of β-Estradiol and bacterial lipopolysaccharide (LPS) on hTERT-HM gene expression were evaluated by western blotting. Results We have reported for the first time the expression and processing of ghrelin, GHS-R1, GOAT and PC1\\/3 expression in human myometrium, and also the down-regulation of ghrelin mRNA and protein expression during labour. Furthermore, GHS-R1 protein expression significantly decreased at labour. Myometrial GOAT expression significantly increased during term non-labouring pregnancy in comparison to both non-pregnant and labouring myometrium. Mature PC1\\/3 protein expression was significantly decreased at term pregnancy and labour in comparison to non-pregnant myometrium. Ghrelin, GHS-R1, GOAT and PC1\\/3 mRNA and protein expression was also detected in the hTERT-HM cells. Ghrelin protein expression decreased upon LPS treatment in these cells while β-Estradiol treatment increased GHS-R1 expression. Conclusions Ghrelin processing occurred in the human

  9. Ghrelin in the human myometrium.

    LENUS (Irish Health Repository)

    O'Brien, Margaret

    2010-01-01

    BACKGROUND: Ghrelin is a 28-amino acid octanolyated peptide, synthesised primarily in the stomach. It stimulates growth hormone release, food intake and exhibits many other diverse effects. Our group have previously determined that ghrelin inhibited human contractility in vitro. The aim of this study therefore, was to investigate the expression of ghrelin, its receptor, the growth hormone secretagogue receptor type 1 (GHS-R1), ghrelin O-acyltransferase (GOAT) which catalyses ghrelin octanoylation, prohormone convertase 1\\/3 (PC1\\/3) responsible for pro-ghrelin processing, in human myometrium, during pregnancy prior to labour, during labour and in the non-pregnant state. Modulation of ghrelin and ghrelin receptor expression in cultured myometrial cells was also investigated. METHODS: mRNA and protein were isolated from human myometrium and the myometrial smooth muscle cell line hTERT-HM; and real-time fluorescence RT-PCR, western blotting and fluorescence microscopy performed. The effects of beta-Estradiol and bacterial lipopolysaccharide (LPS) on hTERT-HM gene expression were evaluated by western blotting. RESULTS: We have reported for the first time the expression and processing of ghrelin, GHS-R1, GOAT and PC1\\/3 expression in human myometrium, and also the down-regulation of ghrelin mRNA and protein expression during labour. Furthermore, GHS-R1 protein expression significantly decreased at labour. Myometrial GOAT expression significantly increased during term non-labouring pregnancy in comparison to both non-pregnant and labouring myometrium. Mature PC1\\/3 protein expression was significantly decreased at term pregnancy and labour in comparison to non-pregnant myometrium. Ghrelin, GHS-R1, GOAT and PC1\\/3 mRNA and protein expression was also detected in the hTERT-HM cells. Ghrelin protein expression decreased upon LPS treatment in these cells while beta-Estradiol treatment increased GHS-R1 expression. CONCLUSIONS: Ghrelin processing occurred in the human

  10. Reduced plasma total homocysteine concentrations in Type 1 diabetes mellitus is determined by increased renal clearance.

    NARCIS (Netherlands)

    Veldman, B.A.J.; Vervoort, G.M.M.; Blom, H.J.; Smits, P.

    2005-01-01

    INTRODUCTION: Elevated plasma levels of total homocysteine are related to the development of vascular complications. Patients with diabetes mellitus are particularly at risk for the development of these complications. Several factors determine plasma total homocysteine including renal function.

  11. A transient ghrelin surge occurs just before feeding in a scheduled meal-fed sheep.

    Science.gov (United States)

    Sugino, T; Hasegawa, Y; Kikkawa, Y; Yamaura, J; Yamagishi, M; Kurose, Y; Kojima, M; Kangawa, K; Terashima, Y

    2002-07-12

    Ghrelin, a gastric-derived peptide, has recently been identified as an endogenous natural ligand for the growth hormone (GH) secretagogue receptor. However, secretory characteristics of ghrelin are still obscure in ruminants. To investigate the diurnal rhythm in ghrelin secretion and its relationship to GH secretion, plasma ghrelin and GH concentrations were determined in Suffolk rams fed with a roughage diet once daily (Experiment 1). Abrupt increases (Pghrelin occurred just before a meal-feeding compared with that at 1h before feeding, then rapidly fell with a minimum during the feeding. A pulsatile surge (Pghrelin, was observed during the feeding. In Experiment 2, plasma ghrelin and GH were determined in sheep subjected to a pseudo-feeding of 2h to determine whether feed ingestion itself influences ghrelin and GH secretions. Compared with those at 1h before feeding, a tendency of increases (Pghrelin and significant increases (Pghrelin temporally declined within 1h after the start of the pseudo-feeding, and increased again and maintained higher levels during the last period of the pseudo-feeding. These results suggest that the transient surge of ghrelin secretion just before a scheduled meal feeding would not be due to the ingestion of feed, and that a pulsatile increase in plasma GH during the actual- or pseudo-feeding could be induced by the transient ghrelin surge.

  12. Jejunal administration of glucose enhances acyl ghrelin suppression in obese humans.

    Science.gov (United States)

    Tamboli, Robyn A; Sidani, Reem M; Garcia, Anna E; Antoun, Joseph; Isbell, James M; Albaugh, Vance L; Abumrad, Naji N

    2016-07-01

    Ghrelin is a gastric hormone that stimulates hunger and worsens glucose metabolism. Circulating ghrelin is decreased after Roux-en-Y gastric bypass (RYGB) surgery; however, the mechanism(s) underlying this change is unknown. We tested the hypothesis that jejunal nutrient exposure plays a significant role in ghrelin suppression after RYGB. Feeding tubes were placed in the stomach or jejunum in 13 obese subjects to simulate pre-RYGB or post-RYGB glucose exposure to the gastrointestinal (GI) tract, respectively, without the confounding effects of caloric restriction, weight loss, and surgical stress. On separate study days, the plasma glucose curves obtained with either gastric or jejunal administration of glucose were replicated with intravenous (iv) infusions of glucose. These "isoglycemic clamps" enabled us to determine the contribution of the GI tract and postabsorptive plasma glucose to acyl ghrelin suppression. Plasma acyl ghrelin levels were suppressed to a greater degree with jejunal glucose administration compared with gastric glucose administration (P 0.05). Direct exposure of the proximal jejunum to glucose increases acyl ghrelin suppression independent of circulating glucose levels. The enhanced suppression of acyl ghrelin after RYGB may be due to a nutrient-initiated signal in the jejunum that regulates ghrelin secretion.

  13. Changes in total plasma content of electrolytes and proteins with maximal exercise.

    Science.gov (United States)

    Van Beaumont, W.; Strand, J. C.; Petrofsky, J. S.; Hipskind, S. G.; Greenleaf, J. E.

    1973-01-01

    To determine to what extent the increases in concentration of plasma proteins and electrolytes with short maximal work were a result of hemoconcentration, the changes in plasma volume and total content of the plasma constituents were simultaneously evaluated. The results obtained from six human subjects indicated that in comparison to preexercise values there was a net decrease in total content of plasma protein, sodium, and chloride in the first 2 min of the postexercise period, due primarily to a significant loss (13-15%) of plasma fluid. The total plasma potassium content was increased immediately after exercise but was significantly below the preexercise plasma content after 2 min of recovery.

  14. Effects of ghrelin on growth hormone secretion in vivo in ruminants.

    Science.gov (United States)

    Hashizume, Tsutomu; Horiuchi, Mami; Nonaka, Sumie; Kasuya, Etsuko; Kojima, Masayasu; Hosoda, Hiroshi; Kangawa, Kenji

    2005-03-15

    Ghrelin, a novel endogenous growth hormone (GH) secretagogue, has been shown to exert very potent and specific GH-releasing activity in rats and humans. However, little is known about its GH-releasing activity and endocrine effects in domestic animals. To clarify the effect of ghrelin on GH secretion in vivo in ruminants, plasma GH responses to intra-arterial and intra-hypothalamic injections of rat ghrelin (rGhrelin) were examined in goats and cattle. The intra-arterial injection of 1 microg/kg BW of rGhrelin in ovariectomized goats failed to stimulate GH release, however, a dosage of 3 microg/kg BW significantly increased plasma GH concentrations (Pghrelin into the medial basal hypothalamus (arcuate nucleus) significantly stimulated the release of GH in male calves (Pghrelin stimulates GH release in ruminants.

  15. Random Lead Time of the acute ghrelin response to a psychological stress

    Directory of Open Access Journals (Sweden)

    Geetha.T

    2014-12-01

    Full Text Available Ghrelin is a growth hormone and cortisol secretagogue that plays an important role in appetite and weight regulation. It is not known whether ghrelin is involved in the eating response to stress in humans. In the present study we examined the effects of psychologically induced stress on plasma ghrelin levels in patients with bingeeating disorder (BED and in healthy subjects of normal or increased body mass index (BMI. Volunteers were subjected to the standardized trier social stress test (TSST. Basal ghrelin levels in patients were at an intermediate level between thin and healthy obese subjects, but this difference did not attain statistical significance. There were no differences in ghrelin levels throughout the test among the groups after correction for BMI, age and gender. A significant difference in the trend time of ghrelin was revealed when the three groups were analyzed according to their cortisol response to stress. Ghrelin levels increased in cortisol responders whereas no change or a decrease in ghrelin levels occurred in cortisol non-responders. We also found Optimal time T*, Minimal Repair δ and Random Lead Time g to minimize the ghrelin level.

  16. Structure and Physiological Actions of Ghrelin

    OpenAIRE

    Christine Delporte

    2013-01-01

    Ghrelin is a gastric peptide hormone, discovered as being the endogenous ligand of growth hormone secretagogue receptor. Ghrelin is a 28 amino acid peptide presenting a unique n-octanoylation modification on its serine in position 3, catalyzed by ghrelin O-acyl transferase. Ghrelin is mainly produced by a subset of stomach cells and also by the hypothalamus, the pituitary, and other tissues. Transcriptional, translational, and posttranslational processes generate ghrelin and ghrelin-related p...

  17. Metabolomic linkage reveals functional interaction between glucose-dependent insulinotropic polypeptide and ghrelin in humans.

    Science.gov (United States)

    Rudovich, Natalia N; Nikiforova, Victoria J; Otto, Baerbel; Pivovarova, Olga; Gögebakan, Ozlem; Erban, Alexander; Möhlig, Matthias; Weickert, Martin O; Spranger, Joachim; Tschöp, Matthias H; Willmitzer, Lothar; Nauck, Michael; Pfeiffer, Andreas F H

    2011-10-01

    The gastric peptide ghrelin promotes energy storage, appetite, and food intake. Nutrient intake strongly suppresses circulating ghrelin via molecular mechanisms possibly involving insulin and gastrointestinal hormones. On the basis of the growing evidence that glucose-dependent insulinotropic polypeptide (GIP) is involved in the control of fuel metabolism, we hypothesized that GIP and/or insulin, directly or via changes in plasma metabolites, might affect circulating ghrelin. Fourteen obese subjects were infused with GIP (2.0 pmol·kg(-1)·min(-1)) or placebo in the fasting state during either euglycemic hyperinsulinemic (EC) or hyperglycemic hyperinsulinemic clamps (HC). Apart from analysis of plasma ghrelin and insulin levels, GC-TOF/MS analysis was applied to create a hormone-metabolite network for each experiment. The GIP and insulin effects on circulating ghrelin were analyzed within the framework of those networks. In the HC, ghrelin levels decreased in the absence (19.2% vs. baseline, P = 0.028) as well as in the presence of GIP (33.8%, P = 0.018). Ghrelin levels were significantly lower during HC with GIP than with placebo, despite insulin levels not differing significantly. In the GIP network combining data on GIP-infusion, EC+GIP and HC+GIP experiments, ghrelin was integrated into hormone-metabolite networks through a connection to a group of long-chain fatty acids. In contrast, ghrelin was excluded from the network of experiments without GIP. GIP decreased circulating ghrelin and might have affected the ghrelin system via modification of long-chain fatty acid pools. These observations were independent of insulin and offer potential mechanistic underpinnings for the involvement of GIP in systemic control of energy metabolism.

  18. Leptin controls rabbit ovarian function in vivo and in vitro: possible interrelationships with ghrelin.

    Science.gov (United States)

    Sirotkin, A V; Rafay, J; Kotwica, J

    2009-10-01

    The aim of these in vivo and in vitro studies was to examine the role of leptin in the control of plasma hormone concentrations, reproduction, and secretory activity of ovarian granulosa cells. In in vivo experiments, 15 female European domestic rabbit (Oryctolagus cuniculus) were treated with leptin (5 microg animal(-1)d(-1) for 1 wk before induction of ovulation with 25 IU equine chorionic gonadotropin and 0.25 IU human chorionic gonadotropin), and 15 females constituted the control group (treated with phosphate-buffered saline). Plasma concentrations of progesterone (P(4)), testosterone (T), estradiol (E(2)), estrone sulfate (ES), and insulin-like growth factor I (IGF-I) were determined at the estimated day of ovulation by radioimmunoassay (RIA), and number, viability, and body weight of newborns were recorded at parturition. In in vitro experiments, granulosa cells were isolated from periovulatory ovarian follicles of five control and five females treated with ghrelin (10 microg animal(-1)d(-1) for 1 wk before induced ovulation). Isolated cells were cultured for 2 d with and without leptin (0, 1, 10, or 100 ng/mL medium). Secretion of P(4), T, E(2), IGF-I, and prostaglandin F (PGF) was assessed in culture medium by RIA. In in vivo experiments, leptin administrations reduced plasma P(4), T, E(2), ES, and IGF-I levels. Leptin treatments did not affect ovarian weight or total number and body mass of newborns, but the proportion of pregnant females and number of live newborns were significantly higher in leptin-treated females than that in control females. In in vitro experiments, leptin significantly decreased (at 1 and 10 ng/mL) or increased (at 100 ng/mL) P(4) secretion, promoted E(2) and IGF-I (both at 100 ng/mL) secretion, and reduced T (at 1 and 10 ng/mL) and PGF (at 10 ng/mL) secretion. Granulosa cells from ghrelin-treated animals secreted less P(4), T, E(2), and PGF, but not IGF-I, than that secreted by granulosa cells from control animals. Furthermore

  19. Hormonal regulation of total antioxidant capacity in seminal plasma.

    Science.gov (United States)

    Mancini, Antonio; Festa, Roberto; Silvestrini, Andrea; Nicolotti, Nicola; Di Donna, Vincenzo; La Torre, Giuseppe; Pontecorvi, Alfredo; Meucci, Elisabetta

    2009-01-01

    Infertility is associated with oxidative stress, normally counterbalanced by different antioxidant systems. In order to explore the hormonal control of seminal plasma total antioxidant capacity (TAC) we evaluated TAC and hormone patterns in a group of unselected infertile patients and control subjects. One hundred and ten infertile patients (divided into 3 groups: inflammation, varicocele, and other etiologies) and 31 fertile men were examined, evaluating blood serum gonadotropins, testosterone, estradiol, free tri-iodothyronine, free tetraiodothyronine (FT4), thyrotropin, prolactin (PRL), seminal parameters, and TAC. TAC was measured using the H(2)O(2)-metmyoglobin system, which generates the spectroscopically detectable radical cation of the chromogenous compound 2,2(I)-azinobis (3-ethylbenzothiazoline-6-sulfonate). The "lag time" of its appearance is proportional to the antioxidant activity. Lag phase was significantly higher in varicocele vs controls, whereas it was lower in patients with inflammation vs varicocele or other kinds of infertility. The correlation analysis between hormones and seminal parameters showed an inverse correlation between PRL and sperm motility, and a direct correlation of TAC with PRL and FT4, but not with gonadotropins or gonadal steroids. Our data suggest that systemic hormones may play a role in regulating seminal antioxidant capacity. This is interesting also because some hormones, such as thyroid and pituitary hormones, are not usually tested in the first-level evaluation of male patients with fertility problems.

  20. The ghrelin/obestatin balance in the physiological and pathological control of growth hormone secretion, body composition and food intake.

    Science.gov (United States)

    Hassouna, R; Zizzari, P; Tolle, V

    2010-07-01

    Ghrelin and obestatin are two gastrointestinal peptides obtained by post-translational processing of a common precursor, preproghrelin. Ghrelin is an orexigenic and adipogenic peptide and a potent growth hormone secretagogue (GHS) modified by the enzyme ghrelin-O-acyl-transferase to bind and activate its receptor, the GHS-R. The ghrelin/GHS-R pathway is complex and the effects of ghrelin on GH secretion, adiposity and food intake appear to be relayed by distinct mechanisms involving different transduction signals and constitutive activity for the GH-R, different cofactors as modulators of endogenous ghrelin signalling and/or alternative ghrelin receptors. The discovery of obestatin in 2005 brought an additional level of complexity to this fascinating system. Obestatin was initially identified as an anorexigenic peptide and as the cognate ligand for GPR39, but its effect on food intake and its ability to activate GPR39 are still controversial. Although several teams failed to reproduce the anorexigenic actions of obestatin, this peptide has been shown to antagonise GH secretion and food intake induced by ghrelin and could be an interesting pharmacological tool to counteract the actions of ghrelin. Ghrelin and obestatin immunoreactivities are recovered in the blood with an ultradian pulsatility and their concentrations in plasma vary with the nutritional status of the body. It is still a matter of debate whether both hormones are regulated by independent mechanisms and whether obestatin is a physiologically relevant peptide. Nevertheless, a significant number of studies show that the ghrelin/obestatin ratio is modified in anorexia nervosa and obesity. This suggests that the ghrelin/obestatin balance could be essential to adapt the body's response to nutritional challenges. Although measuring ghrelin and obestatin in plasma is challenging because many forms of the peptides circulate, more sensitive and selective assays to detect the different preproghrelin

  1. Production of ghrelin by the stomach of patients with gastric cancer.

    Science.gov (United States)

    Kizaki, Junya; Aoyagi, Keishiro; Sato, Takahiro; Kojima, Masayasu; Shirouzu, Kazuo

    2014-01-01

    Poor nutrition and weight loss are important factors contributing to poor quality of life (QOL) after gastrectomy in patients with gastric cancer. Ghrelin is a hormone produced by the stomach that, plays a role in appetite increase and fat storage. The present study aims to clarify the location of ghrelin mRNA in the stomach, changes in blood ghrelin concentrations after gastrectomy and whether or not they are associated with the reconstruction method in patients with gastric cancer. We collected seven normal mucosa samples from different parts of six totally resected stomachs with gastric cancer. We extracted RNA from the normal mucosa, synthesized cDNA from total RNA (1 μg), and then quantified ghrelin mRNA using quantitative real-time polymerase chain reaction (Q-PCR). Ghrelin blood concentrations were measured using enzyme-linked immunosorbent assay (ELISA) kits in 74 patients with gastric cancer (total gastrectomy (TG), n=23; distal gastrectomy (DG), n=30; proximal gastrectomy (PG), n=11; pylorus preserving gastrectomy (PPG), n=10). In order, the ghrelin gene was expressed most frequently in the gastric body, followed by the fornix, cardia, antrum and pylorus ring. Blood ghrelin concentrations after surgery similarly changed in all groups. The average blood ghrelin concentrations were significantly higher in the DG and PPG groups than in the TG group on postoperative days (POD) 1, 7, 30, 90 and 180. However, blood ghrelin concentrations did not significantly differ between the DG and TG groups on POD 270 and 360. Cells that produce ghrelin are supposed to be located mostly in the fundic gland of the stomach. We speculate that the production of ghrelin from other organs increases from around nine months after total gastrectomy. Therefore, evaluating the nutritional status and the weight of patients at nine months after total gastrectomy is important to help these patients improve their QOL.

  2. Sensing of fatty acids for octanoylation of ghrelin involves a gustatory G-protein.

    Directory of Open Access Journals (Sweden)

    Sara Janssen

    Full Text Available BACKGROUND: Ghrelin is an important regulator of energy--and glucose homeostasis. The octanoylation at Ser(3 is essential for ghrelin's biological effects but the mechanisms involved in the octanoylation are unknown. We investigated whether the gustatory G-protein, α-gustducin, and the free fatty acid receptors GPR40 and GPR120 are involved in the fatty acid sensing mechanisms of the ghrelin cell. METHODS: Wild-type (WT and α-gustducin knockout (gust(-/- mice were fed a glyceryl trioctanoate-enriched diet (OD during 2 weeks. Ghrelin levels and gastric emptying were determined. Co-localization between GPR40, GPR120 and ghrelin or α-gustducin/α-transducin was investigated by immunofluorescence staining. The role of GPR120 in the effect of medium and long chain fatty acids on the release of ghrelin was studied in the ghrelinoma cell line, MGN3-1. The effect of the GPR40 agonist, MEDICA16, and the GPR120 agonist, grifolic acid, on ghrelin release was studied both in vitro and in vivo. RESULTS: Feeding an OD specifically increased octanoyl ghrelin levels in the stomach of WT mice but not of gust(-/- mice. Gastric emptying was accelerated in WT but not in gust(-/- mice. GPR40 was colocalized with desoctanoyl but not with octanoyl ghrelin, α-gustducin or α-transducin positive cells in the stomach. GPR120 only colocalized with ghrelin in the duodenum. Addition of octanoic acid or α-linolenic acid to MGN3-1 cells increased and decreased octanoyl ghrelin levels, respectively. Both effects could not be blocked by GPR120 siRNA. MEDICA16 and grifolic acid did not affect ghrelin secretion in vitro but oral administration of grifolic acid increased plasma ghrelin levels. CONCLUSION: This study provides the first evidence that α-gustducin is involved in the octanoylation of ghrelin and shows that the ghrelin cell can sense long- and medium-chain fatty acids directly. GPR120 but not GPR40 may play a role in the lipid sensing cascade of the ghrelin cell.

  3. Ghrelin and gastric acid secretion

    OpenAIRE

    Yakabi, Koji; Kawashima, Junichi; Kato, Shingo

    2008-01-01

    Ghrelin, a novel growth hormone-releasing peptide, was originally isolated from rat and human stomach. Ghrelin has been known to increase the secretion of growth hormone (GH), food intake, and body weight gain when administered peripherally or centrally. Ghrelin is also known to stimulate the gastric motility and the secretion of gastric acid. In the previous studies, the action of ghrelin on acid secretion was shown to be as strong as that of histamine and gastrin in in-vivo experiment. In t...

  4. Ghrelin与胎儿及新生儿生长发育和能量代谢的关系%Relationship between ghrelin,growth and energy balance of fetus and neonate

    Institute of Scientific and Technical Information of China (English)

    梁淑宇; 刘戈力

    2009-01-01

    Ghrelin是生长激素释放激素受体的内源性配体,在胎儿及新生儿生长发育和能量代谢过程中发挥重要作用.胎儿期血循环中ghrelin来源于自身分泌(主要是胰腺,胃分泌较少)和胎盘,既有辛酰基化又有去酰基化ghrelin存在,可直接刺激细胞增殖、骨生长,诱导神经管发生.脐血ghrelin水平明显高于母血,并与胎盘重量、胰岛素样生长因子-1、出生体重及身长呈负相关.新生儿期ghrelin主要由胃黏膜细胞分泌,新生儿肠内营养物质的摄入促进胃肠ghrelin分泌细胞的成熟和分泌.新生儿血清总ghrelin水平高于脐血,并与出生体重、身长呈负相关,小于胎龄儿血ghrelin水平高于正常胎龄儿和大于胎龄儿.%Ghrelin is an endogenous ligand for growth hormone secretngogne receptor. It plays an important role in fetal and neonatal development, and regulate energy balance. In fetus,the major source of circulating ghrelin in blood comes from pancreas and placenta. Both acyl ghrelin and des-acyl ghrelin bind to fetal tissues. They stimulate proliferation of fetal skin cells, bone formation and induce neurogenesis in the dorsal motor nucleus. The level of ghrelin is significantly higher in the umbilical cord blood than in the maternal, and is negatively correlated with placental weight, IGF-1 concentration, birth weight and birth length. In neonate, the source of circulating ghrelin comes from the neuroendocrine cells in the fundus of the stomach. Enteral nutritional intake in neonates contribute to the maturation of ghrelin production in stomach and increased the secretion of ghrelin. The plasma ghrelin level in infants is higher than in cord blood, and is negatively correlated with birth weight and birth length. The total ghrelin level of small-for-gestational age infants is greater than that of appropriate and large-for-gestational age infants.

  5. Ghrelin levels are not regulated by recombinant leptin administration and/or three days of fasting in healthy subjects.

    Science.gov (United States)

    Chan, Jean L; Bullen, John; Lee, Jennifer H; Yiannakouris, Nikos; Mantzoros, Christos S

    2004-01-01

    Ghrelin, a stomach-derived orexigenic peptide, and leptin, a fat-derived anorexigenic hormone, act primarily in the hypothalamus to regulate energy homeostasis and have been reported to be regulated in opposite directions by acute and chronic changes in nutritional state. Nutritional, anthropometric, and hormonal predictors of circulating ghrelin have not yet been fully elucidated, and whether ghrelin is regulated by leptin in humans remains unknown. To address these questions, we performed cross-sectional and interventional studies. In 120 healthy men and women, ghrelin was negatively associated with leptin as well as overall and central adiposity, but not with total energy or specific macronutrient intake. The sexual dimorphism in ghrelin levels (higher levels in women than in men) and the negative correlation between ghrelin and insulin are largely mediated by central adiposity. In six lean men, complete fasting for 3 d resulted in a low leptin state without a major change in fat mass and abolished the meal-related secretory pattern of ghrelin without increasing 24-h ghrelin levels. In addition, recombinant human leptin administration in physiological and pharmacological doses did not regulate ghrelin over several hours to a few days. These data do not support a role for regulation of circulating ghrelin by leptin levels independently of changes in adiposity and suggest that the leptin and ghrelin systems for energy homeostasis function independently of each other in healthy humans.

  6. Serum ghrelin; a new surrogate marker of gastric mucosal alterations in upper gastrointestinal carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Alireza Sadjadi

    Full Text Available BACKGROUND: A few studies have indicated inverse relationships between serum ghrelin and gastric and esophageal cancers but those associations have been restricted to specific populations, including smokers and overweight individuals. We examined the association between ghrelin and gastroesophageal cancers and atrophic gastritis in a population-based setting. METHODS: In total 220 gastroesophageal cancers, comprising non-cardia and cardia gastric cancer, esophageal adenocarcinoma, esophageal squamous cell carcinoma (SCC and age and gender-matched controls were recruited. Serum ghrelin, pepsinogen I/II ratio (PGI/II and anti-H.pylori IgG antibodies were measured. Relationships between ghrelin and gastroesophageal cancers, after adjustment for PGI/II ratio, H.pylori status and smoking, were tested using logistic regression. Furthermore, in 125 endoscopically normal volunteers, with and without histological atrophic gastritis, the relationship with ghrelin was compared. RESULTS: Serum ghrelin (lowest vs. highest quintile was inversely associated with gastric cancer: OR (95% CI 8.71 (1.70-44.59 for cardia and 6.58 (1.26-34.46 for non-cardia cancer. Lower serum ghrelin was also associated with esophageal SCC: OR (95% CI 5.69 (1.36-23.78, but not with esophageal adenocarcinoma. A similar association was observed between gastric cancer (cardia and non-cardia and esophageal SCC when serum ghrelin was analysed as a continuous scaled variable. In endoscopically-normal volunteers, extensive atrophic gastritis was associated with low serum ghrelin [OR (95% CI 0.25 (0.10-0.64]. CONCLUSION: Inverse associations between ghrelin and some gastroesophageal cancers suggest a potential role for serum ghrelin as a biomarker of upper gastrointestinal cancers and atrophic gastritis. In areas with a high incidence of gastric and/or esophageal cancer, screening might be more effectively targeted to individuals with low serum ghrelin in addition to the PGI/II ratio.

  7. Plasma YKL-40 and total and disease-specific mortality in the general population

    DEFF Research Database (Denmark)

    Johansen, Julia S; Bojesen, Stig E; Tybjaerg-Hansen, Anne

    2010-01-01

    Increased plasma YKL-40 is associated with short-term survival in patients with cardiovascular disease and cancer. We tested the hypothesis that increased plasma YKL-40 is associated with total and disease-specific mortality in the general population....

  8. Plasma total antioxidant capacity is associated with dietary intake and plasma level of antioxidants in postmenopausal women.

    Science.gov (United States)

    Wang, Ying; Yang, Meng; Lee, Sang-Gil; Davis, Catherine G; Kenny, Anne; Koo, Sung I; Chun, Ock K

    2012-12-01

    Increased plasma total antioxidant capacity (TAC) has been associated with a high consumption of fruits and vegetables. However, limited information is available on whether plasma TAC reflects the dietary intake of antioxidants and the levels of individual antioxidants in plasma. By using three different assays, the study aimed to determine if plasma TAC can effectively predict dietary intake of antioxidants and plasma antioxidant status. Forty overweight and apparently healthy postmenopausal women were recruited. Seven-day food records and 12-h fasting blood samples were collected for dietary and plasma antioxidant assessments. Plasma TAC was determined by vitamin C equivalent antioxidant capacity (VCEAC), ferric-reducing ability of plasma (FRAP) and oxygen radical absorbance capacity (ORAC) assays. TAC values determined by VCEAC were highly correlated with FRAP (r=0.79, Pantioxidants and represents more closely the plasma antioxidant levels than ORAC and FRAP.

  9. Plasma obestatin concentrations are negatively correlated with body mass index, insulin resistance index, and plasma leptin concentrations in obesity and anorexia nervosa.

    Science.gov (United States)

    Nakahara, Toshihiro; Harada, Toshiro; Yasuhara, Daisuke; Shimada, Nobuhiro; Amitani, Haruka; Sakoguchi, Takeo; Kamiji, Mayra Mayumi; Asakawa, Akihiro; Inui, Akio

    2008-08-01

    Obestatin is a recently identified ghrelin gene product that was reported to inhibit appetite and gastric motility in contrast to ghrelin. We investigated fasting obestatin and ghrelin levels in patients with obesity and anorexia nervosa. Fasting plasma obestatin, acyl-ghrelin, desacyl-ghrelin, leptin, glucose serum adiponectin, and insulin were measured in 10 obese subjects, 11 restricting-type anorexics, and 11 control subjects. Obese group had significantly lower levels of obestatin (p assessment of insulin resistance (HOMA-R) (r = -.49) and was positively correlated with acyl-ghrelin (r = .65) and desacyl-ghrelin (r = .60). No correlation was seen between obestatin and adiponectin, but the latter was negatively correlated with both acyl-ghrelin and desacyl-ghrelin. Desacyl-ghrelin to acyl-ghrelin ratio was significantly different between anorexic and control groups (p nutritional marker reflecting body adiposity and insulin resistance.

  10. Rikkunshito and ghrelin secretion.

    Science.gov (United States)

    Takeda, Hiroshi; Muto, Shuichi; Nakagawa, Koji; Ohnishi, Shunsuke; Asaka, Masahiro

    2012-01-01

    Rikkunshito is a kampo herbal medicine which is widely used in Japan for the treatment of the upper gastrointestinal symptoms of patients with functional dyspepsia (FD), gastroesophageal reflux disease (GERD), dyspeptic symptoms of postgastrointestinal surgery patients, and chemotherapy-induced dyspepsia in cancer patients. Recently, very unique characteristics of rikkunshito have been unveiled; oral administration of rikkunshito potentiates orexigenic action of ghrelin through several different mechanisms. In addition, several lines of evidence obtained from both animal and human studies indicate that rikkunshito can be an attractive and promising therapeutic option for the anorectic conditions including cisplatin-induced dyspepsia, anorexia of aging, stress-induced hypophagia, cancer cachexia-anorexia syndrome. In this review, we will highlight what is known about the orexigenic effect of rikkunshito with a special focus on an interaction with ghrelin signaling system.

  11. Drinking water to reduce alcohol craving? A randomized controlled study on the impact of ghrelin in mediating the effects of forced water intake in alcohol addiction.

    Science.gov (United States)

    Koopmann, Anne; Lippmann, Katharina; Schuster, Rilana; Reinhard, Iris; Bach, Patrick; Weil, Georg; Rietschel, Marcella; Witt, Stephanie H; Wiedemann, Klaus; Kiefer, Falk

    2017-08-05

    Recent data suggest that ghrelin is involved in the pathophysiology of alcohol use disorders, affecting alcohol self-administration and craving. Gastric ghrelin secretion is reduced by stomach distension. We now tested the hypothesis whether the clinically well-known effects of high-volume water intake on craving reduction in alcoholism is mediated by acute changes in ghrelin secretion. In this randomized human laboratory study, we included 23 alcohol-dependent male inpatient subjects who underwent alcohol cue exposure. Participants of the intervention group drank 1000ml of mineral water within 10min directly thereafter, compared to the participants of the control group who did not. Craving and plasma concentrations of acetylated ghrelin were measured ten times during the 120min following the alcohol cue exposure session. In the intervention group, a significant decrease in acetylated ghrelin in plasma compared to the control group was observed. This decrease was correlated to a reduction in patients' subjective level of craving. In the control group, no decrease of acetylated ghrelin in plasma and no association between alcohol craving and changes in plasma concentrations of acetylated ghrelin were observed. Our results present new evidence that the modulation in the ghrelin system by oral water intake mediates the effects of volume intake with craving reduction in alcohol use disorders. Hence, in addition to pharmacological interventions with ghrelin antagonists, the reduction of physiological ghrelin secretion might be a target for future interventions in the treatment of alcohol craving. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. PLATELET RICH PLASMA (PRP) APPLICATION IN TOTAL KNEE ARTHROPLASTY (TKA)

    OpenAIRE

    2015-01-01

    PURPOSE: To find out the PRP application effects in TKA on pain syndrome, wound healing, postoperative blood loss, range of motion and the knee circumference (centimetry). MATERIAL AND METHOD: The preparation of the platelet-rich plasma is based on our treatment algorithm. 20 patients have been subject to TKA within the period from October 2012 to November 2014 and underwent TKA, as platelet rich plasma was used intraoperatively. The average patient age is 72,3; 9 male and 11 female patien...

  13. Changes in Ghrelin-Related Factors in Gastroesophageal Reflux Disease in Rats

    Directory of Open Access Journals (Sweden)

    Miwa Nahata

    2013-01-01

    Full Text Available To examine gastrointestinal hormone profiles and functional changes in gastroesophageal reflux disease (GERD, blood levels of the orexigenic hormone ghrelin were measured in rats with experimentally induced GERD. During the experiment, plasma acyl ghrelin levels in GERD rats were higher than those in sham-operated rats, although food intake was reduced in GERD rats. Although plasma levels of the appetite-suppressing hormone leptin were significantly decreased in GERD rats, no changes were observed in cholecystokinin levels. Repeated administration of rat ghrelin to GERD rats had no effect on the reduction in body weight or food intake. Therefore, these results suggest that aberrantly increased secretion of peripheral ghrelin and decreased ghrelin responsiveness may occur in GERD rats. Neuropeptide Y and agouti-related peptide mRNA expression in the hypothalamus of GERD rats was significantly increased, whereas proopiomelanocortin mRNA expression was significantly decreased compared to that in sham-operated rats. However, melanin-concentrating hormone (MCH and prepro-orexin mRNA expression in the hypothalamus of GERD rats was similar to that in sham-operated rats. These results suggest that although GERD rats have higher plasma ghrelin levels, ghrelin signaling in GERD rats may be suppressed due to reduced MCH and/or orexin synthesis in the hypothalamus.

  14. Underlying Mechanism of Aconitum Lizhong Acting on Experimental Hypothermia with Indigestion in Rats: Role of Ghrelin

    Directory of Open Access Journals (Sweden)

    Xin Zhao

    2012-01-01

    Full Text Available This study is aimed to investigate the Aconitum Lizhong pill (ALZ pharmacological actions on hypothermia with indigestion, especially the ghrelin roles. The littermate-matched rats were randomly divided into four groups. Control did sham operation or standard diet, Model carried out interscapular brown adipose (IBA removal with standard diet, Fat-diet did IBA removal with fat-diet, and ALZ did IBA removal and fat-diet with 4.536 g/kg/d ALZ. The potency of adaptive thermogenesis, ghrelin levels in plasma or gastric mucosa, thyroid hormones and metabolite in sera, expression of ghrelin mRNA, and protein in gastric mucous membrane were determined. ALZ relieved the hypothermia processes with indigestion, via inhibiting ghrelin expression and increasing ghrelin secretion; the dynamics from the therapy is supported with the energy changes as less body weight loss, less plasma lipid decrease, more plasma T3 or T4 increase with TSH decrease, and more compensation of thermogenic AUC decrease. Ghrelin played key roles in the actions of ALZ on the hypothermia with indigestion. The pharmacological mechanisms of ALZ involved the homeostasis of ghrelin expression and secretion.

  15. DESACYL GHRELIN INHIBITS THE OREXIGENIC EFFECT OF PERIPHERALLY INJECTED GHRELIN IN RATS

    Science.gov (United States)

    Inhoff, Tobias; Mönnikes, Hubert; Noetzel, Steffen; Stengel, Andreas; Goebel, Miriam; Dinh, Q. Thai; Riedl, Andrea; Bannert, Norbert; Wisser, Anna-Sophia; Wiedenmann, Bertram; Klapp, Burghard F.; Taché, Yvette

    2008-01-01

    Studies showed that the metabolic unlike the neuroendocrine effects of ghrelin could be abrogated by co-administered unacylated ghrelin. The aim was to investigate the interaction between ghrelin and desacyl ghrelin administered intraperitoneally on food intake and neuronal activity (c-Fos) in the arcuate nucleus in non-fasted rats. Ghrelin (13 μg/kg) significantly increased food intake within the first 30 min post injection. Desacyl ghrelin at 64 and 127 μg/kg injected simultaneously with ghrelin abolished the stimulatory effect of ghrelin on food intake. Desacyl ghrelin alone at both doses did not alter food intake. Both doses of desacyl ghrelin injected separately in the light phase had no effects on food intake when rats were fasted for 12 h. Ghrelin and desacyl ghrelin (64 μg/kg) injected alone increased the number of Fos positive neurons in the arcuate nucleus compared to vehicle. The effect on neuronal activity induced by ghrelin was significantly reduced when injected simultaneously with desacyl ghrelin. Double labeling revealed that nesfatin-1 immunoreactive neurons in the arcuate nucleus are activated by simultaneous injection of ghrelin and desacyl ghrelin. These results suggest that desacyl ghrelin suppresses ghrelin-induced food intake by curbing ghrelin-induced increased neuronal activity in the arcuate nucleus and recruiting nesfatin-1 immunopositive neurons. PMID:18938204

  16. Fasting levels of ghrelin covary with the brain response to food pictures.

    Science.gov (United States)

    Kroemer, Nils B; Krebs, Lena; Kobiella, Andrea; Grimm, Oliver; Pilhatsch, Maximilian; Bidlingmaier, Martin; Zimmermann, Ulrich S; Smolka, Michael N

    2013-09-01

    Ghrelin figures prominently in the regulation of appetite in normal-weighed individuals. The apparent failure of this mechanism in eating disorders and the connection to addictive behavior in general demand a deeper understanding of the endogenous central-nervous processes related to ghrelin. Thus, we investigated processing of pictures showing palatable food after overnight fasting and following a standardized caloric intake (i.e. a 75-g oral glucose tolerance test) using functional magnetic resonance imaging and correlated it with blood plasma levels of ghrelin. Twenty-six healthy female and male volunteers viewed food and control pictures in a block design and rated their appetite after each block. Fasting levels of ghrelin correlated positively with food-cue reactivity in a bilateral network of visual processing-, reward- and taste-related regions, including limbic and paralimbic regions. Notably, among those regions were the hypothalamus and the midbrain where ghrelin receptors are densely concentrated. In addition, high fasting ghrelin levels were associated with stronger increases of subjective appetite during the food-cue-reactivity task. In conclusion, brain activation and subjective appetite ratings suggest that ghrelin elevates the hedonic effects of food pictures. Thereby, fasting ghrelin levels may generally enhance subjective craving when confronted with reward cues.

  17. Effect of ghrelin and thyrotropin-releasing hormone on prolactin secretion in normal women.

    Science.gov (United States)

    Messini, C I; Dafopoulos, K; Chalvatzas, N; Georgoulias, P; Anifandis, G; Messinis, I E

    2010-03-01

    It is known that ghrelin stimulates the secretion of prolactin in women. The aim of this study was to examine the effect of exogenous thyrotropin-releasing hormone (TRH) on ghrelin-induced prolactin release. Ten healthy normally cycling women were studied in four menstrual cycles. The women were injected intravenously in late follicular phase (follicle size 16-17 mm) with a single dose of normal saline (cycle 1), ghrelin (1 microg/kg) (cycle 2), thyrotropin-releasing hormone (200 microg) (cycle 3), and ghrelin plus thyrotropin-releasing hormone (cycle 4). Blood samples in relation to saline or drugs injection (time 0) were taken at -15, 0, 15, 30, 45, 60, 75, 90, and 120 min. The prolactin and growth hormone responses were assessed. After ghrelin administration (cycles 2 and 4), plasma ghrelin, serum prolactin, and growth hormone levels increased rapidly, peaking at 15-30 min (psecretion markedly (pGhrelin induced a smaller prolactin increase than thyrotropin-releasing hormone (pghrelin and thyrotropin-releasing hormone induced a similar increase in prolactin levels as with thyrotropin-releasing hormone alone. No changes in growth hormone and prolactin levels were seen after saline injection. These results demonstrate that the stimulating effect of ghrelin on prolactin secretion is not additive with that of thyrotropin-releasing hormone.

  18. Exogenous ghrelin regulates proliferation and apoptosis in the hypotrophic gut mucosa of the rat.

    Science.gov (United States)

    de Segura, Ignacio A Gómez; Vallejo-Cremades, María Teresa; Lomas, Jesús; Sánchez, Miriam F; Caballero, María Isabel; Largo, Carlota; De Miguel, Enrique

    2010-04-01

    Ghrelin is the natural endogenous ligand for growth hormone secretagogue receptors. This peptide regulates energy homeostasis and expenditure and is a potential link between gut absorptive function and growth. We hypothesized that ghrelin may induce a proliferative and antiapoptotic action promoting the recovery of the hypotrophic gut mucosa. Therefore, the aim of the study was to determine the action of exogenous ghrelin following gut mucosal hypotrophia in rats fed an elemental diet. An elemental diet provides readily absorbable simple nutrients and is usually given to patients with absorptive dysfunction. Male Wistar rats (n = 48) were fed the elemental diet for one week to induce mucosal hypotrophy and then treated for another week with systemic ghrelin and pair-fed with either a normoproteic or hyperproteic isocaloric liquid diet. Another group received a standard diet instead of the elemental diet and served as control (normotrophy). The elemental diet induced intestinal hypotrophia characterized by decreased proliferation in the ileum and increased apoptosis in jejunum and ileum. Ghrelin administration restored normal levels of proliferation in the ileum and apoptosis in the jejunum, with partial apoptosis restoration in the ileum. Ghrelin levels in plasma and fundus were increased in all groups, although the highest levels were found in rats treated with exogenous ghrelin. Ghrelin administration has a positive effect in the hypotrophic gut, regulating both proliferation and apoptosis towards a physiological balance counteracting the negative changes induced by an elemental diet in the intestines.

  19. Acute one-cigarette smoking decreases ghrelin hormone in saliva: a pilot study.

    Science.gov (United States)

    Kaabi, Yahia A; Khalifa, Mohiealdeen A

    2014-01-01

    Cigarette smoking is commonly associated with weight loss and mechanisms for these weight changes are still elusive. Ghrelin is a peptide hormone that works in a neuroendocrine fashion to stimulate hunger and the desire for food intake. Ghrelin is also secreted in saliva, probably to enhance food taste. In the current study, we tested the direct impact of acute cigarette smoking on total ghrelin found in saliva. Methods. Blood and saliva samples were collected from 30 healthy nonsmoker male volunteers before and after one-cigarette smoke. Total ghrelin in serum and saliva was measured by ELISA based method. Results. Data showed a statistically significant reduction in salivary ghrelin after smoking (P < 0.0001). In serum, total ghrelin levels were not affected before and after smoking (P = 0.1362). Additionally, positive correlation was observed between serum and salivary ghrelin before smoking (r = 0.4143 and P = 0.0158); however, this correlation was lost after smoking (r = 0.1147 and P = 0.5461). Conclusion. Acute one-cigarette smoking can negatively affect ghrelin levels in saliva that might contribute to the dull food taste in smokers.

  20. Acute One-Cigarette Smoking Decreases Ghrelin Hormone in Saliva: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Yahia A. Kaabi

    2014-01-01

    Full Text Available Cigarette smoking is commonly associated with weight loss and mechanisms for these weight changes are still elusive. Ghrelin is a peptide hormone that works in a neuroendocrine fashion to stimulate hunger and the desire for food intake. Ghrelin is also secreted in saliva, probably to enhance food taste. In the current study, we tested the direct impact of acute cigarette smoking on total ghrelin found in saliva. Methods. Blood and saliva samples were collected from 30 healthy nonsmoker male volunteers before and after one-cigarette smoke. Total ghrelin in serum and saliva was measured by ELISA based method. Results. Data showed a statistically significant reduction in salivary ghrelin after smoking (P<0.0001. In serum, total ghrelin levels were not affected before and after smoking (P=0.1362. Additionally, positive correlation was observed between serum and salivary ghrelin before smoking (r=0.4143 and P=0.0158; however, this correlation was lost after smoking (r=0.1147 and P=0.5461. Conclusion. Acute one-cigarette smoking can negatively affect ghrelin levels in saliva that might contribute to the dull food taste in smokers.

  1. Ghrelin secretion stimulated by β1-adrenergic receptors in cultured ghrelinoma cells and in fasted mice

    Science.gov (United States)

    Zhao, Tong-Jin; Sakata, Ichiro; Liang, Guosheng; Richardson, James A.; Brown, Michael S.; Goldstein, Joseph L.; Zigman, Jeffrey M.

    2010-01-01

    Ghrelin, an octanoylated peptide hormone produced in the stomach, rises dramatically in mouse plasma during chronic severe calorie deprivation, an event that is essential to maintain life. The mechanism for this increase is not understood. Here, we study the control of ghrelin secretion in tissue culture cells derived from mice bearing ghrelinomas induced by a tissue-specific SV40 T-antigen transgene. We found that the ghrelin-secreting cells express high levels of mRNA encoding β1-adrenergic receptors. Addition of norepinephrine or epinephrine to the culture medium stimulated ghrelin secretion, and this effect was blocked by atenolol, a selective β1-adrenergic antagonist. When WT mice were treated with reserpine to deplete adrenergic neurotransmitters from sympathetic neurons, the fasting-induced increase in plasma ghrelin was blocked. Inhibition was also seen following atenolol administration. We conclude that ghrelin secretion during fasting is induced by adrenergic agents released by sympathetic neurons and acting directly on β1 receptors on the ghrelin-secreting cells of the stomach. PMID:20713709

  2. Ghrelin secretion stimulated by {beta}1-adrenergic receptors in cultured ghrelinoma cells and in fasted mice.

    Science.gov (United States)

    Zhao, Tong-Jin; Sakata, Ichiro; Li, Robert Lin; Liang, Guosheng; Richardson, James A; Brown, Michael S; Goldstein, Joseph L; Zigman, Jeffrey M

    2010-09-07

    Ghrelin, an octanoylated peptide hormone produced in the stomach, rises dramatically in mouse plasma during chronic severe calorie deprivation, an event that is essential to maintain life. The mechanism for this increase is not understood. Here, we study the control of ghrelin secretion in tissue culture cells derived from mice bearing ghrelinomas induced by a tissue-specific SV40 T-antigen transgene. We found that the ghrelin-secreting cells express high levels of mRNA encoding beta(1)-adrenergic receptors. Addition of norepinephrine or epinephrine to the culture medium stimulated ghrelin secretion, and this effect was blocked by atenolol, a selective beta(1)-adrenergic antagonist. When WT mice were treated with reserpine to deplete adrenergic neurotransmitters from sympathetic neurons, the fasting-induced increase in plasma ghrelin was blocked. Inhibition was also seen following atenolol administration. We conclude that ghrelin secretion during fasting is induced by adrenergic agents released by sympathetic neurons and acting directly on beta(1) receptors on the ghrelin-secreting cells of the stomach.

  3. Plasma protein oxidation and total antioxidant power in premenstrual syndrome

    Institute of Scientific and Technical Information of China (English)

    Eans Tara Tuladhar; Anjali Rao

    2010-01-01

    Objective:To explore whether oxidative stress has any role inpremenstrual syndrome (PMS). Methods: Female volunteers suffering from PMS , in the age group of 20-24 years were compared to their asymptomatic normomennorhoeic counterparts in follicular phase and late luteal phase for ferric reducing antioxidant power of plasma(FRAP), plasma protein thiols(PPT) and protein carbonyls(PPC) levels.Results:There was no significant change in FRAP and PPC levels in controls andPMS groups but PPT decreased significantly in luteal phase ofPMS (P< 0.05) when compared to follicular phase.Conclusions:Estrogen and progesterone, might be responsible for a healthy antioxidant profile inPMS. However, a marked decrease inPPT in luteal phase of PMS group may be due to pro-oxidant nature of estrogen-active in this phase of PMS leading to consumption of the sacrificial antioxidant-protein thiol.

  4. Ghrelin and gastrointestinal stromal tumors

    Science.gov (United States)

    Zhu, Chang-Zhen; Liu, Dong; Kang, Wei-Ming; Yu, Jian-Chun; Ma, Zhi-Qiang; Ye, Xin; Li, Kang

    2017-01-01

    Ghrelin, as a kind of multifunctional protein polypeptide, is mainly produced in the fundus of the stomach and can promote occurrence and development of many tumors, including gastrointestinal tumors, which has been proved by the relevant researches. Most gastrointestinal stromal tumors (GISTs, about 80%), as the most common mesenchymal tumor, also develop in the fundus. Scientific research has confirmed that ghrelin, its receptors and mRNA respectively can be found in GISTs, which demonstrated the existence of a ghrelin autocrine/paracrine loop in GIST tissues. However, no reports to date have specified the mechanism whether ghrelin can promote the occurrence and development of GISTs. Studies of pulmonary artery endothelial cells in a low-oxygen environment and cardiac muscle cells in an ischemic environment have shown that ghrelin can activate the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway. Moreover, some studies of GISTs have confirmed that activation of the PI3K/AKT/mTOR pathway can indeed promote the growth and progression of GISTs. Whether ghrelin is involved in the development or progression of GISTs through certain pathways remains unknown. Can we find a new target for the treatment of GISTs? This review explores and summaries the relationship among ghrelin, the PI3K/AKT/mTOR pathway and the development of GISTs.

  5. Leptin, ghrelin, and endocannabinoids

    DEFF Research Database (Denmark)

    Støving, René Klinkby; Andries, Alin; Brixen, Kim;

    2008-01-01

    Anorexia nervosa (AN) has the highest mortality rate between psychiatric disorders, and evidence for managing it is still very limited. So far, pharmacological treatment has focused on a narrow range of drugs and only a few controlled studies have been performed. Furthermore, the studies have been...... molecular targets to control eating behavior has emerged. This review focuses on recent advances in three important signal systems: leptin, ghrelin, and endocannabinoids toward the identification of potential therapeutical breakthroughs in AN. Our review of the current literature shows that leptin may have...

  6. Oxytocin and dopamine stimulate ghrelin secretion by the ghrelin-producing cell line, MGN3-1 in vitro.

    OpenAIRE

    Iwakura, Hiroshi; Ariyasu, Hiroyuki; Hosoda, Hiroshi; Yamada, Go; Hosoda, Kiminori; Nakao, Kazuwa; Kangawa, Kenji; Akamizu, Takashi

    2011-01-01

    To understand the physiological role of ghrelin, it is crucial to study both the actions of ghrelin and the regulation of ghrelin secretion. Although ghrelin actions have been extensively revealed, the direct factors regulating ghrelin secretion by ghrelin-producing cells (X/A-like cells), however, is not fully understood. In this study, we examined the effects of peptide hormones and neurotransmitters on in vitro ghrelin secretion by the recently developed ghrelin-producing cell line MGN3-1....

  7. Novel Molecular Aspects of Ghrelin and Leptin in the Control of Adipobiology and the Cardiovascular System

    Directory of Open Access Journals (Sweden)

    Amaia Rodríguez

    2014-03-01

    Full Text Available Ghrelin and leptin show opposite effects on energy balance. Ghrelin constitutes a gut hormone that is secreted to the bloodstream in two major forms, acylated and desacyl ghrelin. The isoforms of ghrelin not only promote adiposity by the activation of hypothalamic orexigenic neurons but also directly stimulate the expression of several fat storage-related proteins in adipocytes, including ACC, FAS, LPL and perilipin, thereby stimulating intracytoplasmic lipid accumulation. Moreover, both acylated and desacyl ghrelin reduce TNF-α-induced apoptosis and autophagy in adipocytes, suggesting an anti-inflammatory role of ghrelin in human adipose tissue. On the other hand, leptin is an adipokine with lipolytic effects. In this sense, leptin modulates via PI3K/Akt/mTOR the expression of aquaglyceroporins such as AQP3 and AQP7 that facilitate glycerol efflux from adipocytes in response to the lipolytic stimuli via its translocation from the cytosolic fraction (AQP3 or lipid droplets (AQP7 to the plasma membrane. Ghrelin and leptin also participate in the homeostasis of the cardiovascular system. Ghrelin operates as a cardioprotective factor with increased circulating acylated ghrelin concentrations in patients with left ventricular hypertrophy (LVH causally related to LV remodeling during the progression to LVH. Additionally, leptin induces vasodilation by inducible NO synthase expression (iNOS in the vascular wall. In this sense, leptin inhibits the angiotensin II-induced Ca2+ increase, contraction and proliferation of VSMC through NO-dependent mechanisms. Together, dysregulation of circulating ghrelin isoforms and leptin resistance associated to obesity, type 2 diabetes, or the metabolic syndrome contribute to cardiometabolic derangements observed in these pathologies.

  8. Changes in blood pancreatic polypeptide and ghrelin concentrations in response to feeding in sheep.

    Science.gov (United States)

    Takahashi, H; Kurose, Y; Suzuki, Y; Kojima, M; Yamaguchi, T; Yoshida, Y; Azuma, Y; Sugino, T; Kojima, M; Kangawa, K; Hasegawa, Y; Kobayashi, S

    2010-06-01

    The roles of pancreatic polypeptide (PP) have not been determined in ruminant animals. The aim of the present study was to examine the role of PP in the regulation of ghrelin secretion in sheep. Two experiments were conducted using four 2-yr-old Suffolk wethers fed a maintenance diet of alfalfa hay cubes. In Exp. 1, the effects of feeding on blood ghrelin and PP concentrations were examined in scheduled-fed sheep. Blood samples were collected every 10 min from 30 min before to 360 min after feeding. Plasma PP concentrations were transiently increased from the preprandial average value to the values from 30 to 60 min after feeding and gradually decreased (P infusion on ghrelin secretion were examined in feed-deprived sheep. The animals were deprived of feed for 48 h before PP infusion. The PP-treated group intravenously received synthetic bovine PP at a rate of 10 pmol.kg(-1 )of BW.min(-1) for 180 min. Blood samples were collected every 10 min from 30 min before to 180 min after the commencement of PP infusion. Plasma PP concentrations reached a plateau within 30 min after the commencement of PP infusion. Plasma ghrelin concentrations were decreased (P = 0.002, 0.016, 0.007) by PP infusion at 160, 170, and 180 min, respectively. In conclusion, plasma ghrelin and PP concentrations were decreased and increased, respectively, in response to feeding in ruminant animals. Furthermore, PP could depress ghrelin secretion.

  9. PLATELET RICH PLASMA (PRP APPLICATION IN TOTAL KNEE ARTHROPLASTY (TKA

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    Pencho Kosev

    2015-07-01

    Full Text Available PURPOSE: To find out the PRP application effects in TKA on pain syndrome, wound healing, postoperative blood loss, range of motion and the knee circumference (centimetry. MATERIAL AND METHOD: The preparation of the platelet-rich plasma is based on our treatment algorithm. 20 patients have been subject to TKA within the period from October 2012 to November 2014 and underwent TKA, as platelet rich plasma was used intraoperatively. The average patient age is 72,3; 9 male and 11 female patients. Control group consisted of 17 patients, who underwent surgery in the same period but no platelet rich plasma was used during surgery. Average patient age 73,1; 8 male and 9 female patients. RESULTS: The following results have been reported for the PRP group of patients: the average amount of blood in the aspiration drainage tube in 24 hours - 285 ml.; postoperative pain on the 1st postoperative day was - 7 p., on the 5th day - 5 p., on the 10th day - 2 p., average circumference (centimetry of the knee between the 1st and the 10th postoperative day decreased on average by 1,5-2 cm., range of motion – reported average degrees per patient on the 1st postoperative day in sagittal plane: 0-10-20 degrees; on the 10th postoperative day: 0-0-55 degrees, surgical wounds of all patients healed primarily without any complications. No PRP group: average amount of blood in the aspiration drainage in 24 hours – 300 pl., postoperative pain on the 1st, 5th , and 10th postoperative day - 8 p., on the 5th day - 6 p., on the 10th day - 3 p., average knee circumference (centimetry between 1 and 10 postoperative day has decreased by 1 cm on average, range of motion - reported average degrees per patient on the 1st postoperative day in sagittal plane 0-5-20 degrees, on the 10th: 0-0-50 degrees, surgical wounds healed primarily without any complications in 10 patients, but in 7 patients we observed superficial wound edge skin necrosis. CONCLUSION: Our results unequivocally

  10. Ghrelin Facilitates GLUT2-, SGLT1- and SGLT2-mediated Intestinal Glucose Transport in Goldfish (Carassius auratus)

    Science.gov (United States)

    Blanco, Ayelén Melisa; Bertucci, Juan Ignacio; Ramesh, Naresh; Delgado, María Jesús; Valenciano, Ana Isabel; Unniappan, Suraj

    2017-01-01

    Glucose homeostasis is an important biological process that involves a variety of regulatory mechanisms. This study aimed to determine whether ghrelin, a multifunctional gut-brain hormone, modulates intestinal glucose transport in goldfish (Carassius auratus). Three intestinal glucose transporters, the facilitative glucose transporter 2 (GLUT2), and the sodium/glucose co-transporters 1 (SGLT1) and 2 (SGLT2), were studied. Immunostaining of intestinal sections found colocalization of ghrelin and GLUT2 and SGLT2 in mucosal cells. Some cells containing GLUT2, SGLT1 and SGLT2 coexpressed the ghrelin/growth hormone secretagogue receptor 1a (GHS-R1a). Intraperitoneal glucose administration led to a significant increase in serum ghrelin levels, as well as an upregulation of intestinal preproghrelin, ghrelin O-acyltransferase and ghs-r1 expression. In vivo and in vitro ghrelin treatment caused a concentration- and time-dependent modulation (mainly stimulatory) of GLUT2, SGLT1 and SGLT2. These effects were abolished by the GHS-R1a antagonist [D-Lys3]-GHRP-6 and the phospholipase C inhibitor U73122, suggesting that ghrelin actions on glucose transporters are mediated by GHS-R1a via the PLC/PKC signaling pathway. Finally, ghrelin stimulated the translocation of GLUT2 into the plasma membrane of goldfish primary intestinal cells. Overall, data reported here indicate an important role for ghrelin in the modulation of glucoregulatory machinery and glucose homeostasis in fish. PMID:28338019

  11. Rikkunshito and Ghrelin

    Directory of Open Access Journals (Sweden)

    Tomohisa Hattori

    2010-01-01

    Full Text Available Rikkunshito is a popular Japanese traditional medicine that is prescribed in Japan to treat various gastrointestinal tract disorders. In a double-blind controlled study, rikkunshito significantly ameliorated dysmotility-like dyspepsia and brought about a generalized improvement in upper gastric symptoms such as nausea and anorexia when compared with a control group. Several studies in rats have shown enhanced gastric emptying and a protective effect on gastric mucosa injury with rikkunshito administration. In addition, rikkunshito in combination with an anti-emetic drug is effective against anorexia and vomiting that occur as adverse reactions to chemotherapy in patients with advanced breast cancer. However, the mechanism by which rikkunshito alleviates gastrointestinal disorders induced by anticancer agents remains unclear. It has recently been shown that rikkunshito ameliorates cisplatin-induced anorexia by mediating an increase in the circulating ghrelin concentration. Moreover, Fujitsuka et al. found that decreased contractions of the antrum and duodenum in rats treated with a selective serotonin reuptake inhibitor were reversed by rikkunshito via enhancement of the circulating ghrelin concentration. These findings show that rikkunshito may be useful for treatment of anorexia and may provide a new strategy for improvement of upper gastrointestinal dysfunction.

  12. THE EFFECTS OF Syzygium aromaticum-DERIVED TRITERPENES ON GASTROINTESTINAL GHRELIN EXPRESSION IN STREPTOZOTOCIN-INDUCED DIABETIC RATS.

    Science.gov (United States)

    Luvuno, Mluleki; Mbongwa, Hlengiwe Prosperity; Khathi, Andile

    2016-01-01

    Diabetic polyphagia has been associated with elevated plasma ghrelin levels in experimental type 1 diabetes. This increase in food consumption contributes to chronic hyperglycaemia in diabetes thus contributing to the development of micro- and macrovascular complications. We have reported that plant-derived oleanolic acid (OA) and maslinic acid (MA) reduce blood glucose levels, in part, through the inhibition of intestinal carbohydrate hydrolyzing enzymes and glucose transporters. However, their effects on food intake and plasma ghrelin concentrations are unclear. Accordingly, we investigated the effects of these triterpenes on food intake and ghrelin expression in streptozotocin-induced diabetic rats. The effects of OA and MA on blood glucose concentration; food and water intake were monitored over five weeks after which plasma ghrelin concentrations were measured. Additionally, the expression of ghrelin in the various sections of the GIT was determined using Western blot analysis. Ghrelin concentrations in untreated STZ-induced diabetic rats were significantly higher in comparison to the non-diabetic control. Interestingly, the administration of OA and MA reduced food intake, blood glucose levels and plasma ghrelin levels in STZ-induced diabetic rats. This was further complemented by significant reductions in the gastrointestinal expression of ghrelin suggesting that the anti-diabetic properties of these triterpenes are mediated, in part, through the reduction of food intake and the modulation of ghrelin expression. The findings of the study suggest that the control of food intake through the reduction of ghrelin expression by plant-derived OA and MA may constitute an avenue of glycaemic control in diabetes mellitus.

  13. Ghrelin Levels in Children with Constitutional Delay of Growth and Puberty

    OpenAIRE

    Şen, Tolta Altuğ; Gökşen Şimşek, Damla; Darcan, Şükran; Çoker, Mahmut

    2010-01-01

    Objective: In this study, we aimed to show the role of ghrelin in growth delay in children with constitutional delay of growth and puberty (CDGP). Methods: Thirty male children with CDGP constituted the study group and fifteen healthy children with normal growth of similar ages−the control group. In both groups, fasting and postprandial plasma ghrelin levels, serum insulin−like growth factor−1 (IGF−1) and IGF−binding protein−3 (IGFBP−3) levels were determined. Results: There were no differenc...

  14. Activation of somatostatin 2 receptors in the brain and the periphery induces opposite changes in circulating ghrelin levels: functional implications

    Directory of Open Access Journals (Sweden)

    Andreas eStengel

    2013-01-01

    Full Text Available Somatostatin is an important modulator of neurotransmission in the central nervous system and acts as a potent inhibitor of hormone and exocrine secretion and regulator of cell proliferation in the periphery. These pleiotropic actions occur through interaction with five G-protein coupled somatostatin receptor subtypes (sst1-5 that are widely expressed in the brain and peripheral organs. The characterization of somatostatin’s effects can be investigated by pharmacological or genetic approaches using newly developed selective sst agonists and antagonists and mice lacking specific sst subtypes. Recent evidence points towards a divergent action of somatostatin in the brain and in the periphery to regulate circulating levels of ghrelin, an orexigenic hormone produced by the endocrine X/A-like cells in the gastric mucosa. Somatostatin interacts with the sst2 in the brain to induce an increase in basal ghrelin plasma levels and counteracts the visceral stress-related decrease in circulating ghrelin in rats. By contrast, stimulation of peripheral somatostatin-sst2 signaling results in the inhibition of basal ghrelin release and mediates the postoperative decrease in circulating ghrelin in rats. The peripheral sst2-mediated reduction of plasma ghrelin is likely to involve a paracrine action of D-cell derived somatostatin acting on sst2 bearing X/A-like ghrelin cells in the gastric mucosa. The other member of the somatostatin family, named cortistatin, in addition to binding to sst1-5 also directly interacts with the ghrelin receptor and therefore may simultaneously modulate ghrelin release and actions at target sites bearing ghrelin receptors representing a link between the ghrelin and somatostatin systems.

  15. Effect of sulfite treatment on total antioxidant capacity, total oxidant status, lipid hydroperoxide, and total free sulfydryl groups contents in normal and sulfite oxidase-deficient rat plasma.

    Science.gov (United States)

    Herken, Emine Nur; Kocamaz, Erdogan; Erel, Ozcan; Celik, Hakim; Kucukatay, Vural

    2009-08-01

    Sulfites, which are commonly used as preservatives, are continuously formed in the body during the metabolism of sulfur-containing amino acids. Sulfite oxidase (SOX) is an essential enzyme in the pathway of the oxidative degradation of sulfite to sulfate protecting cells from sulfite toxicity. This article investigated the effect of sulfite on total antioxidant capacity (TAC), total oxidant status, lipid hydroperoxide (LOOH), and total free sulfydryl groups (-SH) levels in normal and SOX-deficient male albino rat plasma. For this purpose, rats were divided into four groups: control, sulfite-treated, SOX-deficient, and sulfite-treated SOX-deficient groups. SOX deficiency was established by feeding rats a low molybdenum diet and adding to their drinking water 200 ppm tungsten. Sulfite (70 mg/kg) was administered to the animals via their drinking water. SOX deficiency together with sulfite treatment caused a significant increase in the plasma LOOH and total oxidant status levels. -SH content of rat plasma significantly decreased by both sulfite treatment and SOX deficiency compared to the control. There was also a significant decrease in plasma TAC level by sulfite treatment. In conclusion, sulfite treatment affects the antioxidant/oxidant balance of the plasma cells of the rats toward oxidants in SOX-deficient groups.

  16. What is the general action of ghrelin for vertebrates? - comparisons of ghrelin's effects across vertebrates.

    Science.gov (United States)

    Kaiya, Hiroyuki; Kangawa, Kenji; Miyazato, Mikiya

    2013-01-15

    Ten years and more passed since ghrelin was discovered. Various physiological actions of ghrelin have been documented in both mammalian and nonmammalian vertebrates. Do these actions have any commonality? In this review, we focused on several effects of ghrelin, and compared the effect across vertebrates. We would like to discuss possible general function of ghrelin in vertebrates.

  17. Ghrelin counteracts salt-induced hypertension via promoting diuresis and renal nitric oxide production in Dahl rats.

    Science.gov (United States)

    Aoki, Hirotaka; Nakata, Masanori; Dezaki, Katsuya; Lu, Ming; Gantulga, Darambazar; Yamamoto, Keiji; Shimada, Kazuyuki; Kario, Kazuomi; Yada, Toshihiko

    2013-01-01

    Ghrelin is the endogenous ligand for the growth hormone-secretagogue receptor expressed in various tissues including the heart, blood vessels and kidney. This study sought to determine the effects of long-term treatment with ghrelin (10 nmol/kg, twice a day, intraperitoneally) on the hypertension induced by high salt (8.0% NaCl) diet in Dahl salt-sensitive hypertensive (DS) rats. Systolic blood pressure (SBP) was measured by a tail cuff method. During the treatment period for 3 weeks, high salt diet increased blood pressure compared to normal salt (0.3% NaCl) diet, and this hypertension was partly but significantly (P<0.01) attenuated by simultaneous treatment with ghrelin. Ghrelin significantly increased urine volume and tended to increase urine Na⁺ excretion. Furthermore, ghrelin increased urine nitric oxide (NO) excretion and tended to increase renal neuronal nitric oxide synthase (nNOS) mRNA expression. Ghrelin did not alter the plasma angiotensin II level and renin activity, nor urine catecholamine levels. Furthermore, ghrelin prevented the high salt-induced increases in heart thickness and plasma ANP mRNA expression. These results demonstrate that long-term ghrelin treatment counteracts salt-induced hypertension in DS rats primarily through diuretic action associated with increased renal NO production, thereby exerting cardio-protective effects.

  18. Treatment with pioglitazone is associated with decreased preprandial ghrelin levels: a randomized clinical trial.

    Science.gov (United States)

    Taslimi, Shervin; Esteghamati, Alireza; Rashidi, Armin; Tavakkoli, Hosein Moin; Nakhjavani, Manouchehr; Kebriaee-Zadeh, Abbas

    2013-02-01

    The effects of metformin and pioglitazone on ghrelin, a physiologic regulator of appetite and food intake, have not been clearly established. In a randomized clinical trial, we randomly assigned 60 type 2 diabetic patients to either metformin (Group A; n=30) or pioglitazone (Group B; n=30) treatment groups. The groups were similar in their baseline characteristics. A standard fasting 75 g oral glucose tolerance test was performed at time zero before starting metformin or pioglitazone, and 3 months later. After 3 months of treatment, pioglitazone, but not metformin, was significantly associated with weight gain. Both groups experienced a significant reduction in fasting plasma glucose (ppioglitazone group had a significant reduction in preprandial ghrelin levels after treatment (ppioglitazone on ghrelin was independent of changes in body weight, body mass index, glucose control, insulin resistance, and plasma insulin. In conclusion, treatment with pioglitazone is associated with a decrease in preprandial ghrelin levels and therefore, the weight gain and increased food intake related to pioglitazone use cannot be explained by its effects on ghrelin. The effect of pioglitazone on ghrelin is independent of changes in body weight, body mass index, plasma insulin, insulin resistance, or glucose control.

  19. Unacylated Ghrelin is associated with the isolated low HDL-cholesterol obese phenotype independently of insulin resistance and CRP level

    Directory of Open Access Journals (Sweden)

    Nogueira Juan-Patricio

    2012-03-01

    Full Text Available Abstract Background Low plasma high-density lipoprotein-cholesterol (HDL-c level is commonly present in obesity and represents an independent cardiovascular risk factor. However, obese patients are a very heterogeneous population and the factors and mechanisms that contribute to low HDL-c remain unclear. The aim of this study was to investigate the association between plasma HDL-c levels and plasma hormonal profiles (insulin, adiponectin, resistin, leptin and ghrelin in subsets of class II and III obese patients. Methods Fasting plasma levels of glucose, total cholesterol, LDL-c, HDL-c, triglycerides, free fatty acids, apoproteins A-I, B-100, B-48, C-II, C-III, insulin, hs-CRP, adipocytokines (adiponectin, resistin, leptin, unacylated ghrelin, body composition (DXA and resting energy expenditure were measured in three subsets of obese patients: 17 metabolically abnormal obese (MAO with metabolic syndrome and the typical metabolic dyslipidaemia, 21 metabolically healthy obese (MHO without metabolic syndrome and with a normal lipid profile, and 21 isolated low HDL-c obese patients (LHO without metabolic syndrome, compared to 21 healthy lean control subjects. Results Insulin resistance (HOMA-IR increased gradually from MHO to LHO and from LHO to MAO patients (p p = 0.032. Conclusions These results suggest that, in class II and III obese patients with an isolated low HDL-c phenotype, unacylated ghrelin is positively associated with HDL-c level independently of insulin resistance and CRP levels, and may contribute to the highly prevalent low HDL-c level seen in obesity.

  20. Photoperiod influences the central effects of ghrelin on food intake, GH and LH secretion in sheep.

    Science.gov (United States)

    Harrison, Joanne L; Miller, David W; Findlay, Patricia A; Adam, Clare L

    2008-01-01

    Ghrelin is a circulating peptide, primarily secreted by the gut, that has reported actions within the hypothalamo-pituitary axis to stimulate food intake, inhibit GnRH/LH secretion and stimulate GH secretion in monogastric species. Here, we examine responses to centrally administered ghrelin in a seasonal ruminant. Estradiol-implanted castrated male sheep with indwelling intracerebroventricular (i.c.v.) cannulae were kept with unrestricted food for 16 weeks in long day photoperiod (LD, 16 h light/day) then 16 weeks in short days (SD, 8 h light/day). In week 16 of each photoperiod they were given a control (saline) i.c.v. injection on day 1 and ghrelin i.c.v. injection on day 2. Mean circulating endogenous plasma ghrelin concentrations showed no diurnal pattern and were similar between the photoperiods. Central ghrelin injection increased voluntary food intake 2-fold in the first hour after administration in LD but not in SD, decreased LH pulse frequency and amplitude in SD but not in LD, and stimulated GH release in both photoperiods, although there was a 1.5-fold larger response in LD. Therefore, central injection of ghrelin to sheep acutely stimulated food intake in LD, suppressed reproductive neuroendocrine output in SD, and stimulated GH secretion irrespective of photoperiod, although more pronounced in LD. These data indicate that photoperiod can influence hypothalamic appetite and reproductive neuroendocrine responses to ghrelin in seasonal species.

  1. Ghrelin enhances glucose-induced insulin secretion in scheduled meal-fed sheep.

    Science.gov (United States)

    Takahashi, H; Kurose, Y; Kobayashi, S; Sugino, T; Kojima, M; Kangawa, K; Hasegawa, Y; Terashima, Y

    2006-04-01

    The purpose of this study was to investigate the effects of physiologic levels of ghrelin on insulin secretion and insulin sensitivity (glucose disposal) in scheduled fed-sheep, using the hyperglycemic clamp and hyperinsulinemic euglycemic clamp respectively. Twelve castrated Suffolk rams (69.8 +/- 0.6 kg) were conditioned to be fed alfalfa hay cubes (2% of body weight) once a day. Three hours after the feeding, synthetic ovine ghrelin was intravenously administered to the animals at a rate of 0.025 and 0.05 mug/kg body weight (BW) per min for 3 h. Concomitantly, the hyperglycemic clamp or the hyperinsulinemic euglycemic clamp was carried out. In the hyperglycemic clamp, a target glucose concentration was clamped at 100 mg/100 ml above the initial level. In the hyperinsulinemic euglycemic clamp, insulin was intravenously administered to the animals for 3 h at a rate of 2 mU/kg BW per min. Basal glucose concentrations (44+/- 1 mg/dl) were maintained by variably infusing 100 mg/dl glucose solution. In both clamps, plasma ghrelin concentrations were dose-dependently elevated and maintained at a constant level within the physiologic range. Ghrelin infusions induced a significant (ANOVA; P ghrelin-infused animals. In the hyperinsulinemic euglycemic clamp, glucose infusion rate, an index of insulin sensitivity, was not affected by ghrelin infusion. In conclusion, the present study has demonstrated for the first time that ghrelin enhances glucose-induced insulin secretion in the ruminant animal.

  2. Circulating ghrelin was negatively correlated with pulmonary arterial pressure in atrial septal defect patients

    Institute of Scientific and Technical Information of China (English)

    LI Zhao-feng; ZHOU Da-xin; PAN Wen-zhi; ZHANG Lei; GE Jun-bo

    2013-01-01

    Background Ghrelin was found to attenuate the magnitude of pulmonary arterial hypertension and pulmonary vascular remodeling in rats.The objective of this study was to explore the fasting plasma ghrelin level and the relationships between ghrelin and pulmonary arterial pressure (PAP) in atrial septal defect (ASD) patients with pulmonary arterial hypertension (PAH).Methods Fasting plasma ghrelin,obestatin,and insulin levels were measured by enzyme linked immunosorbent assay (ELISA) method in ASD patients with or without PAH according to the manufacturer's instructions.Insulin resistance was calculated by the homeostasis model of assessment for insulin resistance (HOMA-IR) approach,calculated as fasting insulin (microunits/ml)× fasting blood glucose (mmol/L)/22.5.Comparisons between the parameters of patients with PAH and those of patients with normal PAP were performed with an unpaired Student's t test.The relationships between ghrelin and various clinical parameters were examined by bivariate correlations and multiple regression analysis.Results We found that the fasting plasma ghrelin level and the ratio of ghrelin to obestatin were significantly lower in the PAH group compared with the control group ((582.4±12.8) pg/ml vs.(1045.2±95.5) pg/ml,P <0.05 and 30.5±4.9 vs.70.0±9.7,P <0.01).The fasting plasma obestatin level was higher in the PAH group compared with the control group,but the difference between them was not significant ((23.2±3.1) pg/ml vs.(16.3±1.6) pg/ml,P >0.05).In a multiple regression model analysis,only mean PAP was an independent predictor of ghrelin and the ratio of ghrelin to obestatin (standardized coefficient=0.737,P <0.001 and standardized coefficient=-0.588,P=0.006,respectively).Conclusion Ghrelin is negatively correlated with mean PAP and this suggests that circulating ghrelin might predict the severity of pulmonary hypertension in ASD patients with PAH.

  3. Acetylcholine regulates ghrelin secretion in humans

    NARCIS (Netherlands)

    F. Broglio (Fabio); E. Ghigo (Ezio); C. Gottero; F. Prodam (Flavia); S. Destefanis; A. Benso; C. Gauna (Carlotta); L.J. Hofland (Leo); E. Arvat; A-J. van der Lely (Aart-Jan); P.M. van Koetsveld (Peter)

    2004-01-01

    textabstractGhrelin secretion has been reportedly increased by fasting and energy restriction but decreased by food intake, glucose, insulin, and somatostatin. However, its regulation is still far from clarified. The cholinergic system mediates some ghrelin actions, e.g.

  4. Exenatide Treatment Causes Suppression of Serum Ghrelin Levels following Mixed Meal Test in Obese Diabetic Women

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    Figen Topyildiz

    2016-01-01

    Full Text Available Aim. To investigate the effect of exenatide treatment on serum ghrelin levels in obese female patients with type 2 diabetes mellitus. Methods. Fourteen female patients with type 2 diabetes mellitus being treated with metformin and exenatide were enrolled. A mixed meal test was applied to the patients while continuing with their daily medications. Blood samples were taken before and at 60, 120, and 180 minutes following mixed meal test to measure serum total ghrelin, glucose, and insulin levels. The following week, exenatide treatment of the patients was paused for 24 hours and the same experimental procedures were repeated. Results. Serum ghrelin levels were suppressed significantly at 180 minutes with exenatide treatment compared with baseline (294.4±57.5 versus 234.5±59.4 pg/mL (p<0.001. Serum ghrelin levels at 180 minutes were statistically different when percentage change in serum ghrelin levels after mixed meal tests with and without exenatide usage were compared (p=0.001. Estimated total area under the curve values for serum ghrelin concentrations was also significantly lower with exenatide compared with omitted treatment (p=0.035. Conclusion. These results suggest that the effect of exenatide on weight loss may be related with the suppression of serum ghrelin levels, which is an orexigenic peptide.

  5. Influence of etanercept on leptin and ghrelin secretion in children with juvenile idiopathic arthritis.

    Science.gov (United States)

    Maciejewska-Paszek, Izabela; Grochowska-Niedworok, Elżbieta; Siwiec, Andrzej; Gruenpeter, Anna; Dul, Lechosław; Irzyniec, Tomasz

    2017-04-01

    Objective To assess possible changes in leptin and ghrelin secretion due to etanercept in juvenile idiopathic arthritis (JIA). Methods 50 patients with JIA and 16 age-matched controls were enrolled into this prospective, cross-sectional study. Serum leptin, total and acyl ghrelin were measured in addition to white blood cell (WBC) and lymphocyte counts. Results 25 patients received etanercept and 25 conventional therapies (including methotrexate) for JIA. There was no difference between treatment and control groups in leptin or ghrelin levels and no evidence of a relationship between leptin and ghrelin in patients with JIA. In all children with JIA there was a correlation between leptin and body mass index (BMI). However, compared with children in the conventional treatment group, children in the etanercept group showed a positive correlation between total ghrelin and BMI and those with a low BMI showed a negative correlation between acyl ghrelin and BMI. Conclusion No differences in leptin and ghrelin concentrations were found when patients with JIA and controls were compared or when patients who received etanercept were compared with those who received conventional treatment for JIA.

  6. Ghrelin: Central and Peripheral Implications in Anorexia Nervosa

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    Mathieu eMéquinion

    2013-02-01

    Full Text Available Food intake and associated disorders are gaining large emphasis in our societies due to their dramatic physiological and psychological consequences on health. Chronic food restriction is a major symptom described in restrictive anorexia nervosa (AN patients. This disease, mostly observed in young women is the third cause of chronic illness in teenagers. It leads to central and/or peripheral reprogramming that permits the organism to endure the reduced energy supplies. These drastic conditions induce severe weight loss, metabolic disturbances, infertility, osteopenia and osteoporosis. Moreover, increasing number of arguments consider AN as an addictive behaviour to food deprivation or weight loss or physical activity, usually associated with mood disorders. This suggests a potential alteration of the central reward system. Significant changes in hormones involved in energy metabolism, regulation of feeding behaviours and bone formation are described in AN patients, but also in animal models presenting a strong face validity. Surprisingly, the plasma levels of ghrelin, an orexigenic hormone, are increased. This hormone acts centrally to modulate food intake, but also peripherally mainly to maintain blood glucose and to regulate gastric motility. Such increase in plasma ghrelin levels seems paradoxical in light of the restrained eating adopted by these AN patients, but adaptive. The aim of this review is to describe the role played by ghrelin in AN focusing on its central vs peripheral action. The chronic food restriction induces both in AN patients and in rodent models a profound alteration in the « ghrelin » signal integration that lead to the development of inappropriate behaviours like hyperactivity or addiction to food starvation and therefore a greater depletion in energy reserves. The question of a transient insensitivity to ghrelin and/or a potential metabolic reprogramming is discussed in regard of new clinical treatments currently

  7. Ghrelin modulates sympathetic nervous system activity and stress response in lean and overweight men.

    Science.gov (United States)

    Lambert, Elisabeth; Lambert, Gavin; Ika-Sari, Carolina; Dawood, Tye; Lee, Katie; Chopra, Reena; Straznicky, Nora; Eikelis, Nina; Drew, Sara; Tilbrook, Alan; Dixon, John; Esler, Murray; Schlaich, Markus P

    2011-07-01

    Ghrelin is a growth hormone-releasing peptide secreted by the stomach with potent effects on appetite. Experimental and clinical studies indicate that ghrelin also influences cardiovascular regulation and metabolic function and mediates behavioral responses to stress. We investigated the effects of ghrelin on blood pressure (BP), sympathetic nervous system activity, and mental stress responses in lean (n=13) and overweight or obese (n=13) individuals. Subjects received an intravenous infusion of human ghrelin (5 pmol/kg per minute for 1 hour) and saline in a randomized fashion. Ghrelin decreased systolic (-6 and -11 mm Hg) and diastolic BP (-8 mm Hg for both), increased muscle sympathetic nervous system activity (18±2 to 28±3 bursts per min, P<0.05 and from 21±2 to 32±3 bursts per min, P<0.001) in lean and overweight or obese subjects, respectively, without a significant change in heart rate, calf blood flow, or vascular resistance. Ghrelin induced a rise in plasma glucose concentration in lean individuals (P<0.05) and increased cortisol levels in both groups (P<0.05). Stress induced a significant change in mean BP (+22 and +27 mm Hg), heart rate (+36 and +29 bpm), and muscle sympathetic nervous system activity (+6.1±1.6 and +6.8±2.7 bursts per min) during saline infusion in lean and overweight or obese subjects, respectively. During ghrelin infusion, the changes in BP and muscle sympathetic nerve activity in response to stress were significantly reduced in both groups (P<0.05). In conclusion, ghrelin exerts unique effects in that it reduces BP and increases muscle sympathetic nervous system activity and blunts cardiovascular responses to mental stress. These responses may represent a combination of peripheral (baroreflex-mediated) and central effects of ghrelin.

  8. EFFECTS OF ENDURANCE RUNNING AND DIETARY FAT ON CIRCULATING GHRELIN AND PEPTIDE YY

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    Enette D. Larson-Meyer

    2009-12-01

    Full Text Available Ghrelin and peptide YY (PYY are newly recognized gut peptides involved in appetite regulation. Plasma ghrelin concentrations are elevated in fasting and suppressed following a meal, while PYY concentrations are suppressed in fasting and elevated postprandially. We determine whether ghrelin and PYY are altered by a low-fat, high-carbohydrate (10% fat, 75% carbohydrate or moderate-fat, moderate-carbohydrate (35% fat, 50% carbohydrate diet and; whether these peptides are affected by intense endurance running (which is likely to temporarily suppress appetite. Twenty-one endurance-trained runners followed a controlled diet (25% fat and training regimen for 3 days before consuming the low-fat or isoenergetic moderate-fat diet for another 3 days in random cross-over fashion. On day 7 runners underwent glycogen restoration and then completed a 90-minute pre-loaded 10-km time trial on day 8, following a control breakfast. Blood samples were obtained on days 4 and 7 (fasting, and day 8 (non-fasting before and after exercise for analysis of ghrelin, PYY, insulin and growth hormone (GH. Insulin, GH, Ghrelin and PYY changed significantly over time (p < 0.0001 but were not influenced by diet. Ghrelin was elevated during fasting (days 4 and 7, while insulin and PYY were suppressed. Following the pre-exercise meal, ghrelin was suppressed ~17% and insulin and PYY were elevated ~157 and ~40%, respectively, relative to fasting (day 7. Following exercise, PYY, ghrelin, and GH were significantly (p < 0.0001 increased by ~11, ~16 and ~813%, respectively. The noted disruption in the typical inverse relationship between ghrelin and PYY following exercise suggests that interaction of these peptides may be at least partially responsible for post-exercise appetite suppression. These peptides do not appear to be influenced by dietary fat intake

  9. Ghrelin: much more than a hunger hormone

    Science.gov (United States)

    Ghrelin is a multifaceted gut hormone that activates its receptor, growth hormone secretagogue receptor (GHS-R). Ghrelin's hallmark functions are its stimulatory effects on growth hormone release, food intake and fat deposition. Ghrelin is famously known as the 'hunger hormone'. However, ample recen...

  10. Thermogenic characterization of ghrelin receptor null mice

    Science.gov (United States)

    Ghrelin is the only known circulating orexigenic hormone that increases food intake and promotes adiposity, and these physiological functions of ghrelin are mediated through its receptor growth hormone secretagogue receptor (GHS-R). Ghrelin/GHS-R signaling plays a crucial role in energy homeostasis....

  11. Increased plasma carnitine in trauma patients given lipid-supplemented total parenteral nutrition.

    Science.gov (United States)

    Davis, A T; Albrecht, R M; Scholten, D J; Morgan, R E

    1988-12-01

    The purpose of this study was to determine the effects of altering the fuel substrate mix of total parenteral nutrition (TPN) on plasma and urinary carnitine in trauma patients. TPN solutions were either 100% carbohydrate (CHO) based or lipid based (70% CHO, 30% lipid). There were statistically significant (p less than 0.05) increases in plasma levels of free carnitine, short-chain acyl carnitine, and total carnitine in trauma patients receiving lipid-based TPN. No significant differences in urinary carnitine excretion were noted between groups. We conclude that the use of lipids in the TPN of trauma patients leads to an alteration in plasma carnitine metabolism.

  12. Negative energy balance increases periprandial ghrelin and growth hormone concentrations in lactating dairy cows.

    Science.gov (United States)

    Bradford, Barry J; Allen, Michael S

    2008-02-01

    The reported effects of feeding on growth hormone (GH) secretion in ruminants have been inconsistent, and are likely influenced by energy status of animals. High-producing dairy cows in early lactation and late lactation were used to assess the effects of energy balance on temporal variation of plasma metabolites and hormones. Cows were fed a single diet once daily, and feed was withdrawn for 90 min prior to feeding. Beginning at the time of feed withdrawal, plasma samples were collected via jugular catheters hourly for 24h. Concentrations of non-esterified fatty acids and GH were measured for all samples, while insulin, glucose, and acylated (active) ghrelin were quantified for four sample times around feeding. As expected, calculated energy balance was significantly lower in early lactation than late lactation cows (-43.5 MJ retained/day versus 7.2 MJ retained/day). Following the primary meal of the day, a GH surge was observed in early lactation but not in late lactation cows. This difference was not explained by temporal patterns in non-esterified fatty acid, insulin, or glucose concentrations. However, a preprandial ghrelin surge was observed in early lactation only, suggesting that ghrelin was responsible for the prandial GH surge in this group. Results of a stepwise regression statistical analysis showed that both preprandial ghrelin concentration and energy balance were significant predictors of prandial GH increase over baseline. Adaptations to negative energy balance in lactating dairy cattle likely include enhanced ghrelin secretion and greater GH response to ghrelin.

  13. Effects of ghrelin on psychopathology, sleep and secretion of cortisol and growth hormone in patients with major depression.

    Science.gov (United States)

    Kluge, Michael; Schüssler, Petra; Dresler, Martin; Schmidt, Doreen; Yassouridis, Alexander; Uhr, Manfred; Steiger, Axel

    2011-03-01

    Ghrelin showed antidepressant-like effects in mice. Furthermore, ghrelin influences sleep and the activity of hypothalamic-pituitary-adrenal (HPA) and somatotropic axis in healthy humans as indicated by increased cortisol and growth hormone (GH) plasma levels. Both sleep and the activity of these endocrine axes are disturbed in depression. We therefore studied the impact of ghrelin on psychopathology, sleep and secretion of cortisol and GH in patients with major depression. Depressive symptoms as assessed by a validated self rating scale ('Befindlichkeits-Skala', [mental state scale]), secretion profiles of cortisol and GH and sleep-EEGs were determined in 14 unmedicated patients with major depression (7 women) twice, receiving 50 μg ghrelin or placebo at 22:00, 23:00, 00:00, and 01:00 hours. Overall, depressive symptoms did not change significantly after ghrelin administration (placebo: 37 ± 8; ghrelin: 33 ± 10, p = 0.178). However, there was an improvement at trend level in men (placebo: 36 ± 9 to ghrelin: 30 ± 9, p = 0.093) but not in women. In men, ghrelin was associated with less time awake (placebo: 149.0 ± 11.1; ghrelin: 88.0 ± 12.2 min, p = 0.029) and more non-REM sleep (placebo: 263.2 ± 24.1; ghrelin: 304.9 ± 14.1 min, p = 0.027), in women with less REM sleep (placebo: 108.6 ± 15.7; ghrelin: 74.1 ± 13.8 min, p = 0.031) and longer REM latency (placebo: 49.9 ± 6.5; ghrelin: 85.6 ± 14.1 min, p = 0.019). In both sexes, ghrelin caused strong transient increases of GH and cortisol. In conclusion, our study may provide some initial indication that ghrelin can exert antidepressant effects in patients with major depression. Ghrelin strongly affected sleep and secretion of GH and cortisol in a partly different way as previously reported in healthy subjects.

  14. Participation of ghrelin signalling in the reciprocal regulation of hypothalamic NPY/POMC-mediated appetite control in amphetamine-treated rats.

    Science.gov (United States)

    Yu, Ching-Han; Chu, Shu-Chen; Chen, Pei-Ni; Hsieh, Yih-Shou; Kuo, Dong-Yih

    2017-02-14

    Hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) have been documented to participate in amphetamine (AMPH)-induced appetite suppression. This study investigated whether ghrelin signalling is associated with changes in NPY/POMC-mediated appetite control. Rats were given AMPH daily for four days, and changes in food intake, body weight, plasma ghrelin, hypothalamic NPY, melanocortin 3 receptor (MC3R), ghrelin O-acyltransferase (GOAT), acyl ghrelin (AG) and ghrelin receptor (GHSR1a) were examined and compared. Food intake, body weight and NPY expression decreased, while MC3R expression increased and expressed reciprocally to NPY expression during AMPH treatment. Plasma ghrelin and hypothalamic AG/GOAT/GHSR1a expression decreased on Day 1 and Day 2, which was associated with the positive energy metabolism, and returned to normal levels on Day 3 and Day 4, which was associated with the negative energy metabolism; this expression pattern was similar to that of NPY. Infusion with a GHSR1a antagonist or an NPY antisense into the brain enhanced the decrease in NPY and AG/GOAT/GHSR1a expression and the increase in MC3R expression compared to the AMPH-treated group. Peripheral ghrelin and the central ghrelin system participated in the regulation in AMPH-induced appetite control. These results shed light on the involvement of ghrelin signalling in reciprocal regulation of NPY/POMC-mediated appetite control and may prove useful for the development of anti-obesity drugs.

  15. Ghrelin O-Acyl Transferase: Bridging Ghrelin and Energy Homeostasis

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    Andrew Shlimun

    2011-01-01

    Full Text Available Ghrelin O-acyl transferase (GOAT is a recently identified enzyme responsible for the unique n-acyl modification of ghrelin, a multifunctional metabolic hormone. GOAT structure and activity appears to be conserved from fish to man. Since the acyl modification is critical for most of the biological actions of ghrelin, especially metabolic functions, GOAT emerged as a very important molecule of interest. The research on GOAT is on the rise, and several important results reiterating its significance have been reported. Notable among these discoveries are the identification of GOAT tissue expression patterns, effects on insulin secretion, blood glucose levels, feeding, body weight, and metabolism. Several attempts have been made to design and test synthetic compounds that can modulate endogenous GOAT, which could turn beneficial in favorably regulating whole body energy homeostasis. This paper will focus to provide an update on recent advances in GOAT research and its broader implications in the regulation of energy balance.

  16. Organ-specific activation of the gastric branch of the efferent vagus nerve by ghrelin in urethane-anesthetized rats.

    Science.gov (United States)

    Habara, Hiromi; Hayashi, Yujiro; Inomata, Norio; Niijima, Akira; Kangawa, Kenji

    2014-01-01

    Ghrelin plays multiple physiological roles such as growth hormone secretion and exerting orexigenic actions; however, its physiological roles in the electrical activity of autonomic nerves remain unclear. Here, we investigated the effects of human ghrelin on several autonomic nerve activities in urethane-anesthetized rats using an electrophysiological method. Intravenous injection of ghrelin at 3 μg/kg significantly and transiently potentiated the efferent activity of the gastric vagus nerve; however, it did not affect the efferent activity of the hepatic vagus nerve. The activated response to ghrelin in the gastric efferent vagus nerve was not affected by the gastric afferent vagotomy, suggesting that this effect was not induced via the gastric afferent vagus nerve. Ghrelin did not affect the efferent activity of the brown adipose tissue, adrenal gland sympathetic nerve, and the renal sympathetic nerve. In addition, rectal temperature and the plasma concentrations of norepinephrine, corticosterone, and renin were also not changed by ghrelin. These findings demonstrate that ghrelin stimulates the gastric efferent vagus nerve in an organ-specific manner without affecting the gastric afferent vagus nerve and that ghrelin does not acutely affect the efferent basal activity of the sympathetic nerve in rats.

  17. Bicuculline, a GABAA-receptor antagonist, blocked HPA axis activation induced by ghrelin under an acute stress.

    Science.gov (United States)

    Gastón, M S; Cid, M P; Salvatierra, N A

    2017-03-01

    Ghrelin is a peptide of 28 amino acids with a homology between species, which acts on the central nervous system to regulate different actions, including the control of growth hormone secretion and metabolic regulation. It has been suggested that central ghrelin is a mediator of behavior linked to stress responses and induces anxiety in rodents and birds. Previously, we observed that the anxiogenic-like behavior induced by ghrelin injected into the intermediate medial mesopallium (IMM) of the forebrain was blocked by bicuculline (a GABAA receptor competitive antagonist) but not by diazepam (a GABAA receptor allosteric agonist) in neonatal meat-type chicks (Cobb). Numerous studies have indicated that hypothalamic-pituitary-adrenal (HPA) axis activation mediates the response to stress in mammals and birds. However, it is still unclear whether this effect of ghrelin is associated with HPA activation. Therefore, we investigated whether anxiety behavior induced by intra-IMM ghrelin and mediated through GABAA receptors could be associated with HPA axis activation in the neonatal chick. In the present study, in an Open Field test, intraperitoneal bicuculline methiodide blocked anxiogenic-like behavior as well as the increase in plasma ACTH and corticosterone levels induced by ghrelin (30pmol) in neonatal chicks. Moreover, we showed for the first time that a competitive antagonist of GABAA receptor suppressed the HPA axis activation induced by an anxiogenic dose of ghrelin. These results show that the anxiogenic ghrelin action involves the activation of the HPA axis, with a complex functional interaction with the GABAA receptor.

  18. Urocortin 1 reduces food intake and ghrelin secretion via CRF(2) receptors.

    Science.gov (United States)

    Yakabi, Koji; Noguchi, Masamichi; Ohno, Shino; Ro, Shoki; Onouchi, Tsuneko; Ochiai, Mitsuko; Takabayashi, Hidehiko; Takayama, Kiyoshige; Harada, Yumi; Sadakane, Chiharu; Hattori, Tomohisa

    2011-07-01

    Although it is known that urocortin 1 (UCN) acts on both corticotropin-releasing factor receptors (CRF(1) and CRF(2)), the mechanisms underlying UCN-induced anorexia remain unclear. In contrast, ghrelin, the endogenous ligand for the growth hormone secretagogue receptor, stimulates food intake. In the present study, we examined the effects of CRF(1) and CRF(2) receptor antagonists (CRF(1)a and CRF(2)a) on ghrelin secretion and synthesis, c-fos mRNA expression in the caudal brain stem, and food intake following intracerebroventricular administration of UCN. Eight-week-old, male Sprague-Dawley rats were used after 24-h food deprivation. Acylated and des-acylated ghrelin levels were measured by enzyme-linked immunosorbent assay. The mRNA expressions of preproghrelin and c-fos were measured by real-time RT-PCR. The present study provided the following important insights into the mechanisms underlying the anorectic effects of UCN: 1) UCN increased acylated and des-acylated ghrelin levels in the gastric body and decreased their levels in the plasma; 2) UCN decreased preproghrelin mRNA levels in the gastric body; 3) UCN-induced reduction of plasma ghrelin and food intake were restored by CRF(2)a but not CRF(1)a; 4) UCN-induced increase of c-fos mRNA levels in the caudal brain stem containing the nucleus of the solitary tract (NTS) was inhibited by CRF(2)a; and 5) UCN-induced reduction of food intake was restored by exogenous ghrelin and rikkunshito, an endogenous ghrelin secretion regulator. Thus, UCN increases neuronal activation in the caudal brain stem containing NTS via CRF(2) receptors, which may be related to UCN-induced inhibition of both ghrelin secretion and food intake.

  19. X-ray plasma diagnostics for totally and partially photoionized plasmas such as Warm Absorber in AGN

    CERN Document Server

    Porquet, D; Porquet, Delphine; Dubau, Jacques

    1999-01-01

    Thanks to the new generation of X-ray satellites such as Chandra and XMM, high resolution and high sensitivity spectra are available. In particular, for the first time, the three most intense lines (resonance, intercombination and forbidden) of low charged (low Z) He-like ions are splitted for non solar plasmas. We present density, ionizing process and temperature diagnostics, for totally and partially photoionized plasmas, based on ratios of these three lines. These powerful plasma diagnostics could be used for hot astrophysical plasmas such as AGN, starburst galaxies, X-ray binaries, etc. In particular, they could be applied to Warm Absorber often seen in Active Galactic Nuclei (Porquet & Dubau 2000), which is an important key tool to understand central region of different types of AGN (Seyfert 1 and 2, high and low redshift quasars).

  20. Effects of ghrelin on the structural complexity of exocrine pancreas tissue architecture.

    Science.gov (United States)

    Pantic, Igor; Nesic, Dejan; Stevanovic, Darko; Starcevic, Vesna; Pantic, Senka; Trajkovic, Vladimir

    2013-06-01

    Recent studies have shown that ghrelin increases pancreatic exocrine secretion. However, the potential effects of ghrelin on the morphology of exocrine pancreas (EP) remain unknown. In this work, using fractal analysis, we demonstrate that centrally administered ghrelin increases structural complexity and tissue disorder in rat EP. The study was carried out on a total of 40 male Wistar rats divided into four groups (n = 10): ghrelin-treated animals (average age, 1.5 months), ghrelin-treated animals (8.5 months), and controls (1.5 and 8.5 months). The pancreas tissue sections were stained with hematoxylin/eosin and visualized by light microscopy. For each animal, the average values of tissue fractal dimension, lacunarity, as well as parameters of co-occurrence matrix texture, were determined using tissue digital micrographs. The results indicate that ghrelin administration increases EP fractal dimension and textural entropy, and decreases lacunarity, regardless of the age. To our knowledge, this is the first study to investigate the effects of ghrelin on the morphological properties of pancreatic tissue, and also the first to apply fractal and textural analysis methods in quantification of EP tissue architecture.

  1. Serum acylated ghrelin is negatively correlated with the insulin resistance in the CODING study.

    Directory of Open Access Journals (Sweden)

    Peyvand Amini

    Full Text Available OBJECTIVE: Ghrelin is a 28-amino acid orexigenic peptide synthesized mainly in the stomach. Acute administration of ghrelin has been found to decrease insulin secretion. However, little data is available regarding whether ghrelin contributes to the long-term regulation of insulin resistance at the population level. The aim of this study is to investigate the association between circulating ghrelin and insulin resistance in a large population based study. DESIGN: A total of 2082 CODING study (Complex Diseases in the Newfoundland population: Environment and Genetics subjects were assessed. Subjects were of at least third generation Newfoundland descent, between the ages of 20 and 79 years, and had no serious metabolic, cardiovascular, or endocrine diseases. Ghrelin was measured with an Enzyme Immunoassay method. Insulin and fasting glucose were measured by Immulite 2500 autoanalyzer and Lx20 clinical chemistry analyzer, respectively. Homeostatic Model Assessment of β cell function (HOMA-β and Insulin Resistance (HOMA-IR and Quantitative Insulin-sensitivity Check Index (QUICKI were used for measurement of insulin resistance. RESULTS: Partial correlation analyses showed a significant negative correlation between circulating ghrelin and insulin level and insulin resistance in the entire cohort and also in men and women separately. The aforementioned correlation was independent of age, percentage of trunk fat and HDL-cholesterol. According to menopausal status, only pre-menopausal women revealed negative correlations. CONCLUSION: Our results suggest that except for postmenopausal women, high circulating ghrelin level is associated with lower insulin resistance in the general population.

  2. Preprandial ghrelin is not affected by macronutrient intake, energy intake or energy expenditure

    Directory of Open Access Journals (Sweden)

    Rumpler William V

    2005-03-01

    Full Text Available Abstract Background Ghrelin, a peptide secreted by endocrine cells in the gastrointestinal tract, is a hormone purported to have a significant effect on food intake and energy balance in humans. The influence of factors related to energy balance on ghrelin, such as daily energy expenditure, energy intake, and macronutrient intake, have not been reported. Secondly, the effect of ghrelin on food intake has not been quantified under free-living conditions over a prolonged period of time. To investigate these effects, 12 men were provided with an ad libitum cafeteria-style diet for 16 weeks. The macronutrient composition of the diets were covertly modified with drinks containing 2.1 MJ of predominantly carbohydrate (Hi-CHO, protein (Hi-PRO, or fat (Hi-FAT. Total energy expenditure was measured for seven days on two separate occasions (doubly labeled water and physical activity logs. Results Preprandial ghrelin concentrations were not affected by macronutrient intake, energy expenditure or energy intake (all P > 0.05. In turn, daily energy intake was significantly influenced by energy expenditure, but not ghrelin. Conclusion Preprandial ghrelin does not appear to be influenced by macronutrient composition, energy intake, or energy expenditure. Similarly, ghrelin does not appear to affect acute or chronic energy intake under free-living conditions.

  3. Structure and Physiological Actions of Ghrelin

    Directory of Open Access Journals (Sweden)

    Christine Delporte

    2013-01-01

    Full Text Available Ghrelin is a gastric peptide hormone, discovered as being the endogenous ligand of growth hormone secretagogue receptor. Ghrelin is a 28 amino acid peptide presenting a unique n-octanoylation modification on its serine in position 3, catalyzed by ghrelin O-acyl transferase. Ghrelin is mainly produced by a subset of stomach cells and also by the hypothalamus, the pituitary, and other tissues. Transcriptional, translational, and posttranslational processes generate ghrelin and ghrelin-related peptides. Homo- and heterodimers of growth hormone secretagogue receptor, and as yet unidentified receptors, are assumed to mediate the biological effects of acyl ghrelin and desacyl ghrelin, respectively. Ghrelin exerts wide physiological actions throughout the body, including growth hormone secretion, appetite and food intake, gastric secretion and gastrointestinal motility, glucose homeostasis, cardiovascular functions, anti-inflammatory functions, reproductive functions, and bone formation. This review focuses on presenting the current understanding of ghrelin and growth hormone secretagogue receptor biology, as well as the main physiological effects of ghrelin.

  4. Ghrelin family of peptides and gut motility.

    Science.gov (United States)

    Asakawa, Akihiro; Ataka, Koji; Fujino, Kazunori; Chen, Chih-Yen; Kato, Ikuo; Fujimiya, Mineko; Inui, Akio

    2011-04-01

    Acyl ghrelin, des-acyl ghrelin, and obestatin are three peptides isolated from the gastrointestinal tract and encoded by the same preproghrelin gene. Three ghrelin gene products participate in modulating appetite, adipogenesis, glucose metabolism, cell proliferation, immune, sleep, memory, anxiety, cognition, and stress. We have investigated the effects of ghrelin family of peptides on fed and fasted motor activities in the stomach and duodenum of freely moving conscious rats by manometric method. Intracerebroventricular (ICV) and intravenous (IV) administration of acyl ghrelin induced fasted motor activity in the duodenum in fed rats. ICV and IV administration of des-acyl ghrelin disrupted fasted motor activity in the antrum. Changes in gastric motility induced by IV administration of des-acyl ghrelin were antagonized by ICV administration of a corticotropin-releasing factor (CRF) 2 receptor antagonist. IV administration of obestatin decreased the percentage motor index in the antrum and prolonged the time taken to return to fasted motility in the duodenum in fed rats. ICV administration of CRF 1 and 2 receptor antagonists prevented the effects of obestatin on gastroduodenal motility. Ghrelin gene products regulate feeding-associated gastroduodenal motility. Stomach may regulate various functions including gastrointestinal motility via acyl ghrelin, des-acyl ghrelin and obestatin as an endocrine organ. Increasing knowledge of the effects of ghrelin family of peptides on gastrointestinal motility could lead to innovative new therapies for functional gastrointestinal disorders.

  5. Evaluation of the refractometric method for the determination of total protein in avian plasma or serum.

    Science.gov (United States)

    Lumeij, J T; de Bruijne, J J

    1985-07-01

    Serum total protein concentrations in pigeon blood determined with the biuret method (TPB-se) were compared with total protein concentrations in plasma (TPR-pl) and serum (TPR-se) obtained by estimation from refractive index. The refractometric method consistently yielded higher values (Prefractometric method for determination of TP in pigeon blood is not recommended.

  6. Metabolic and Cardiovascular Effects of Ghrelin

    Directory of Open Access Journals (Sweden)

    Manfredi Tesauro

    2010-01-01

    Ghrelin receptors have been detected in the hypothalamus and the pituitary, but also in the cardiovascular system, where ghrelin exerts beneficial hemodynamic activities. Ghrelin administration acutely improves endothelial dysfunction by increasing nitric oxide bioavailability and normalizes the altered balance between endothelin-1 and nitric oxide within the vasculature of patients with metabolic syndrome. Other cardiovascular effects of ghrelin include improvement of left ventricular contractility and cardiac output, as well as reduction of arterial pressure and systemic vascular resistance. In addition, antinflammatory and antiapoptotic actions of ghrelin have been reported both in vivo and in vitro. This review summarizes the most recent findings on the metabolic and cardiovascular effects of ghrelin through GH-dependent and -independent mechanisms and the possible role of ghrelin as a therapeutic molecule for treating cardiovascular diseases.

  7. Ghrelin regulates GLP-1 production through mTOR signaling in L cells.

    Science.gov (United States)

    Xu, Geyang; Hong, Xiaosi; Tang, Hong; Jiang, Sushi; Liu, Fenting; Shen, Zhemin; Li, Ziru; Zhang, Weizhen

    2015-11-15

    Glucagon-like peptide (GLP-1), an intestinal incretin produced in L-cells and released in response to meal intake, functions to promote insulin secretion and to decrease plasma glucose. Ghrelin is an orexigenic hormone critical for glucose homeostasis. The molecular mechanism by which ghrelin alters GLP-1 production remains largely unknown. Here we showed that ghrelin attenuates GLP-1 production through mTOR signaling. In GHSR1a null mice, ileal mTOR signaling, proglucagon and circulating GLP-1 were significantly increased. Antagonism of the GHSR1a by D-Lys-3-GHRP-6 increased GLP-1 synthesis and release in STC-1 cells. Treatment of STC-1 cells with ghrelin decreased the production of GLP-1. This effect was associated with a significant inhibition of mTOR signaling. Overexpression of ghrelin inhibited proglucagon promoter activity and GLP-1 production. Inhibition of mTOR activity by mTOR siRNA blocked D-Lys-3-GHRP-6 induced GLP-1 production in STC-1 cells. Our results suggest that mTOR signaling mediates the inhibitory effect of ghrelin on GLP-1 production.

  8. Bitter taste receptors and α-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying.

    Science.gov (United States)

    Janssen, Sara; Laermans, Jorien; Verhulst, Pieter-Jan; Thijs, Theo; Tack, Jan; Depoortere, Inge

    2011-02-01

    Ghrelin is a hunger hormone with gastroprokinetic properties but the factors controlling ghrelin secretion from the stomach are unknown. Bitter taste receptors (T2R) and the gustatory G proteins, α-gustducin (gust) and α-transducin, are expressed in the gut and are involved in the chemosensation of nutrients. This study aimed to investigate whether T2R-agonists affect (i) ghrelin release via α-gustducin and (ii) food intake and gastric emptying via the release of ghrelin. The mouse stomach contains two ghrelin cell populations: cells containing octanoyl and desoctanoyl ghrelin, which were colocalized with α-gustducin and α-transducin, and cells staining for desoctanoyl ghrelin. Gavage of T2R-agonists increased plasma octanoyl ghrelin levels in WT mice but the effect was partially blunted in gust(-/-) mice. Intragastric administration of T2R-agonists increased food intake during the first 30 min in WT but not in gust(-/-) and ghrelin receptor knockout mice. This increase was accompanied by an increase in the mRNA expression of agouti-related peptide in the hypothalamus of WT but not of gust(-/-) mice. The temporary increase in food intake was followed by a prolonged decrease (next 4 h), which correlated with an inhibition of gastric emptying. The delay in emptying, which was partially counteracted by ghrelin, was not mediated by cholecystokinin and GLP-1 but involved a direct inhibitory effect of T2R-agonists on gastric contractility. This study is unique in providing functional evidence that activation of bitter taste receptors stimulates ghrelin secretion. Modulation of endogenous ghrelin levels by tastants may provide novel therapeutic applications for the treatment of weight -and gastrointestinal motility disorders.

  9. Changes in ghrelin and obestatin levels before and after a meal in children with simple obesity and anorexia.

    Science.gov (United States)

    Shen, Chuan; Yu, Tao; Tang, Zhang Hui; Wu, Kang Min

    2013-01-01

    Obestatin and ghrelin both have effects on the hypothalamus which controls food intake. We hypothesize that the circulating levels of obestatin and ghrelin may change after a meal and might be different between obesity and anorexia, which might be relevant to anorexia or obesity. Fifteen children with obesity, 25 children with anorexia and 17 normal-weight healthy controls were enrolled in the study. The preprandial and postprandial glucose, insulin, total ghrelin and obestatin tests were completed in the three groups. The values of these indices were compared. The obesity group had the highest values for BMI and fasting glucose (p anorexia group had the highest values for obestatin and ghrelin, followed by the control and obesity groups. No differences in ratios of ghrelin to obestatin were found between the anorexia and obesity groups (p > 0.05), but both were higher than that of the control group (p < 0.05). BMI was negatively correlated with preprandial obestatin (r = -0.8413, p < 0.001) and ghrelin (r = -0.7400, p < 0.001), but showed no significant correlations with the ghrelin-to-obestatin ratio. Although there is still controversy between the present and previous studies, the present study show that levels of obestatin and ghrelin are inversely correlated with BMI. Copyright © 2013 S. Karger AG, Basel.

  10. Total plasma protein in very preterm babies: prognostic value and comparison with illness severity scores.

    Directory of Open Access Journals (Sweden)

    Silvia Iacobelli

    Full Text Available OBJECTIVE: We aimed to investigate the predictive value for severe adverse outcome of plasma protein measurements on day one of life in very preterm infants and to compare total plasma protein levels with the validated illness severity scores CRIB, CRIB-II, SNAP-II and SNAPPE-II, regarding their predictive ability for severe adverse outcome. METHODS: We analyzed a cohort of infants born at 24-31 weeks gestation, admitted to the tertiary intensive care unit of a university hospital over 10.5 years. The outcome measure was "severe adverse outcome" defined as death before discharge or severe neurological injury on cranial ultrasound. The adjusted odd ratio (aOR and 95% confidence interval (95% CI of severe adverse outcome for hypoproteinemia (total plasma protein level <40 g/L was calculated by univariate and multivariate analyses. Calibration (Hosmer-Lemeshow goodness-of-fit was performed and the predictive ability for severe adverse outcome was assessed for total plasma protein and compared with CRIB, CRIB-II, SNAP-II and SNAPPE-II, by calculating receiver operating characteristic (ROC curves and their associated area under the curve (AUC. RESULTS: 761 infants were studied: 14.4% died and 4.1% survived with severe cerebral ultrasound findings. The aOR of severe adverse outcome for hypoproteinemia was 6.1 (95% CI 3.8-9.9. The rank order for variables, as assessed by AUCs and 95% CIs, in predicting outcome was: total plasma protein [0.849 (0.821-0.873], SNAPPE-II [0.822 (0.792-0.848], CRIB [0.821 (0.792-0.848], SNAP-II [0.810 (0.780-0.837] and CRIB-II [0.803 (0.772-0.830]. Total plasma protein predicted severe adverse outcome significantly better than CRIB-II and SNAP-II (both p<0.05. Calibration for total plasma protein was very good. CONCLUSIONS: Early hypoproteinemia has prognostic value for severe adverse outcome in very preterm, sick infants. Total plasma protein has a predictive performance comparable with CRIB and SNAPPE-II and greater than

  11. Cortisol and ghrelin concentrations following a cold pressor stress test in overweight individuals with and without Night Eating

    OpenAIRE

    Geliebter, Allan; Carnell, Susan; Gluck, Marci E.

    2012-01-01

    Objective To explore appetite-related hormones following stress in overweight individuals, and their interaction with Night Eating (NE) status. Method We measured plasma cortisol and ghrelin concentrations, and recorded ratings of stress and hunger in response to a physiological laboratory stressor (Cold Pressor Test, CPT) in overweight women with (n=11; NE) and without (n=17; non-NE) night eating. Results Following the CPT, cortisol (p < .001) and ghrelin (p < .05) levels increased, as did s...

  12. Accuracy of plasma turbidity measurement for determining fat intolerance during total parenteral nutrition.

    Science.gov (United States)

    Nordenström, J; Thörne, A; Lindholm, M

    1990-06-01

    The accuracy of plasma turbidity measurements in predicting ability to metabolise intravenous fat emulsions during total parenteral nutrition was studied in 35 adult surgical patients. Plasma turbidity, expressed as a light scattering index (LSI), was determined by nephelometry and compared with measured triglyceride (TG) concentrations. A poor coefficient of correlation was found between LSI and TG (r = 0.52). The sensitivity and specificity of LSI in predicting TG concentration were 19% and 96% respectively. This indicates that the measurement of LSI is more useful in ruling out hypertriglyceridaemia than in detecting it. Consequently, clinical tolerance of intravenous fat emulsion cannot be monitored by measuring plasma turbidity. In order to avoid metabolic complications which may occasionally occur during intravenous nutritional therapy including fat emulsion, determination of plasma TG levels at timed intervals are recommended.

  13. Triterpenes suppress octanoylated ghrelin production in ghrelin-expressing human gastric carcinoma cells.

    Science.gov (United States)

    Nakajima, Kensuke; Oiso, Shigeru; Uto, Takuhiro; Morinaga, Osamu; Shoyama, Yukihiro; Kariyazono, Hiroko

    2016-01-01

    Ghrelin is an appetite-stimulating peptide hormone with an octanoyl modification at serine 3 that is essential for its orexigenic effect. Ghrelin O-acyltransferase (GOAT) is the enzyme that catalyzes ghrelin acylation using fatty acyl-coenzyme A as a substrate. We previously developed an assay system based on the AGS-GHRL8 cell line that produces octanoylated ghrelin in the presence of octanoic acid, and demonstrated that some fatty acids suppressed octanoylated ghrelin production. Recent studies have reported that triterpenes have anti-obesity effect. Since such triterpenes, like fatty acids, have a carboxyl group, we speculated that they can suppress octanoylated ghrelin production. To test this hypothesis, we investigated the effect of triterpenes on octanoylated ghrelin production. Asiatic acid, corosolic acid, glycyrrhetinic acid, oleanolic acid and ursolic acid suppressed octanoylated ghrelin levels in AGS-GHRL8 cells without decreasing transcript expression of GOAT or furin, a protease required for ghrelin maturation. β-amyrin had no effect on octanoylated ghrelin level, which was only slightly inhibited by uvaol; the fact that both these triterpenes lack a carboxyl group indicates that this group is important for suppressing octanoylated ghrelin production. These results suggest that triterpenes may have the potential as obesity-preventing agents with suppressive effect on octanoylated ghrelin production.

  14. Association of ghrelin with cardiometabolic risk factors in Iranian adolescents: the CASPIAN-III study

    Science.gov (United States)

    Heshmat, Ramin; Shafiee, Gita; Qorbani, Mostafa; Azizi-Soleiman, Fatemeh; Djalalinia, Shirin; Esmaeil Motlagh, Mohammad; Ardalan, Gelayol; Ahadi, Zeinab; Safari, Omid; Safiri, Saeid; Kelishadi, Roya

    2016-01-01

    Introduction: Current evidence suggests that ghrelin could contribute to the development of metabolic syndrome (MetS) in adults, but limited experience exists in adolescents. This study aims to explore the association of ghrelin levels with the MetS components among Iranian adolescents. Methods: In this case-control study, 32 adolescents with MetS and 148 healthy controls were selected randomly from the childhood and Adolescence Surveillance and Prevention of Adult Non communicable disease (CASPIAN-III) study. MetS was defined according to the Adult Treatment Panel III (ATP III) criteria modified for children and adolescents. Anthropometric measures (including body mass index [BMI], waist circumference [WC] and waist to height ratio [WHtR]), blood pressure (BP) and biochemical data (including fasting blood sugar [FBS], triglyceride [TG], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC] and gerlin) were measured. Results: Total ghrelin level was significantly higher in students without MetS compared to those with MetS (748.89 ± 85.04 vs. 728.72 ± 90.36 [pg/mL]; P < 0.001). Significant negative correlations were seen between ghrelin levels and BMI, WC, WHtR, TG, and TC. Ghrelin had also relatively strong inverse correlations with FBS (r = −0.59, P< 0.001), LDL-C (r = −0.56, P < 0.001), and positive correlation with HDL-C (r = 0.60, P < 0.001). Compared with the children with MetS, in those without MetS, ghrelin was significantly associated with HDL-C and LDL-C. A decreasing trend was observed in the mean ghrelin level across increasing number of MetS components (P for trend <0.001). Conclusion: We observed a relationship between ghrelin concentration and MetS components in adolescents. PMID:27777695

  15. Effects of plasma total ammonia content and pH on urea excretion in Nile tilapia.

    Science.gov (United States)

    McKenzie, D J; Piraccini, G; Felskie, A; Romano, P; Bronzi, P; Bolis, C L

    1999-01-01

    Nile tilapia (Oreochromis niloticus) were infused with ammonium salts, acid, and base to investigate the effects of changes in arterial plasma total ammonia content (Tamm) and pH (pHa) on plasma urea-nitrogen (urea-N) levels and urea-N excretory fluxes (Jurea-N). The tilapia did not possess a functional hepatic ornithine urea-cycle (no significant carbamyl phosphate synthetase III activity). Infused substances were dissolved in a saline vehicle and injected twice (5 mL kg-1), the first infusion to "prime" the animal and promote a more marked response to the second infusion, given 2.5 h later. The results reported are those of the second infusion. Infusion of 200 mM NH4Cl increased Tamm, reduced pHa, and increased plasma urea-N and Jurea-N. Two hundred mM NH4HCO3 increased Tamm and arterial plasma total CO2 content (TaCO2), reduced pHa, and increased Jurea-N. Fifty mM HCl reduced pHa but had no effects on urea dynamics. Fifty mM NaOH increased pHa, plasma urea-N levels, and Jurea-N. Two hundred mM NaHCO3 increased pHa, TaCO2, plasma urea-N levels, and Jurea-N. Infusion of the saline vehicle was without effect. The results indicate that ammonia loading and plasma alkalosis both stimulate urea excretion in uricolytic fish. The responses to hyperammonemia or alkalosis were not modified when combined with elevated plasma bicarbonate levels.

  16. Total plasma proANP increases with atrial dilatation in horses

    DEFF Research Database (Denmark)

    Van Der Vekens, N; Hunter, I; Timm, A

    2015-01-01

    Equine atrial natriuretic peptide (ANP) plasma concentrations are correlated with left atrial size. However, species-specific assays are lacking and the results from human assays are poorly reproducible. A new methodology called processing independent analysis (PIA) that measures the total pro......ANP product in plasma has proven to be successful in human medicine, but has never been used in horses. The aims were to establish an equine proANP reference interval by measurement of the total proANP product using PIA and to examine the proANP concentrations in horses with atrial dilatation. Sample...... stability was studied by comparison of storage at -80°C and -20°C. Plasma samples were obtained from 23 healthy horses, 12 horses with moderate or severe valvular regurgitation without atrial dilatation and 42 horses with valvular regurgitation and atrial dilatation. The proANP concentration...

  17. Plasma atrial natriuretic peptide after the Fontan procedure and total cavopulmonary connexion.

    Science.gov (United States)

    Burch, M; Shinebourne, E A; Rigby, M L; Carter, N; Jeffery, S; Stanley, P; Smith, A

    1990-05-01

    Plasma atrial natriuretic peptide was measured in 10 children undergoing the Fontan procedure and 3 children undergoing total cavopulmonary connexion. There was no significant difference in pre-operative plasma levels, but post-operative levels were significantly higher 48 hours after cardiopulmonary bypass in the Fontan group. There was no significant difference in plasma arginine vasopressin levels either pre- or post-operatively. Post-operative pleural effusions occurred in only 2 of the 10 patients undergoing the Fontan procedure, but were present in all 3 of those undergoing total cavopulmonary connexion. The release of atrial natriuretic peptide is an appropriate homeostatic response to volume loading and the impairment of this response in the early post-operative period may be of clinical importance.

  18. Ghrelin fluctuation, what determines its production?

    Institute of Scientific and Technical Information of China (English)

    Xuefeng Yin; Yin Li; Geyang Xu; Wenjiao An; Weizhen Zhang

    2009-01-01

    Ghrelin, a 28 amino acid gut brain peptide, acts as an endogenous ligand for its receptor, the growth hormone secretagogue receptor, to exercise a variety of functions ranging from stimulation of growth hormone secretion, regulation of appetite and energy metabolism, and cell protection to modulation of inflammation. This review summarizes the advance in the regulation of ghrelin expression and secretion. We introduce the structure of ghrelin promoter, the processing and modification of ghrelin precursor, and the regulation mechanism in these processes. Then we discuss factors found to be important in the regulation of ghrelin production, including nutrients, hormones, and autonomic nervous system. Finally, we outline the alteration in the level of ghrelin in certain physiological and pathological status.

  19. Spectrophotometric determination of total proteins in blood plasma: a comparative study among dye-binding methods

    OpenAIRE

    Dimas Augusto Morozin Zaia; Fábio Rangel Marques; Cássia Thaïs Bussamra Vieira Zaia

    2005-01-01

    A comparative study between the biuret method (standard method for total proteins) and spectrophotometric methods using dyes (Bradford, 3',3",5',5"-tetrabromophenolphthalein ethyl ester-TBPEE, and erythrosin-B) was carried out for the determination of total proteins in blood plasma from rats. Bradford method showed the highest sensitivity for proteins and biuret method showed the lowest. For all the methods, the absorbance for different proteins (BSA, casein, and egg albumin) was measured and...

  20. Plasma free and total carnitine measured in children by tandem mass spectrometry

    OpenAIRE

    J.H. Osorio; Pourfarzam, M.

    2002-01-01

    Free and total carnitine quantification is important as a complementary test for the diagnosis of unusual metabolic diseases, including fatty acid degradation disorders. The present study reports a new method for the quantification of free and total carnitine in dried plasma specimens by isotope dilution electrospray tandem mass spectrometry with sample derivatization. Carnitine is determined by looking for the precursor of ions of m/z = 103 of N-butylester derivative, and the method is valid...

  1. Ghrelin: Central and Peripheral Implications in Anorexia Nervosa

    Science.gov (United States)

    Méquinion, Mathieu; Langlet, Fanny; Zgheib, Sara; Dickson, Suzanne; Dehouck, Bénédicte; Chauveau, Christophe; Viltart, Odile

    2012-01-01

    Increasing clinical and therapeutic interest in the neurobiology of eating disorders reflects their dramatic impact on health. Chronic food restriction resulting in severe weight loss is a major symptom described in restrictive anorexia nervosa (AN) patients, and they also suffer from metabolic disturbances, infertility, osteopenia, and osteoporosis. Restrictive AN, mostly observed in young women, is the third largest cause of chronic illness in teenagers of industrialized countries. From a neurobiological perspective, AN-linked behaviors can be considered an adaptation that permits the endurance of reduced energy supply, involving central and/or peripheral reprograming. The severe weight loss observed in AN patients is accompanied by significant changes in hormones involved in energy balance, feeding behavior, and bone formation, all of which can be replicated in animals models. Increasing evidence suggests that AN could be an addictive behavior disorder, potentially linking defects in the reward mechanism with suppressed food intake, heightened physical activity, and mood disorder. Surprisingly, the plasma levels of ghrelin, an orexigenic hormone that drives food-motivated behavior, are increased. This increase in plasma ghrelin levels seems paradoxical in light of the restrained eating adopted by AN patients, and may rather result from an adaptation to the disease. The aim of this review is to describe the role played by ghrelin in AN focusing on its central vs. peripheral actions. In AN patients and in rodent AN models, chronic food restriction induces profound alterations in the « ghrelin » signaling that leads to the development of inappropriate behaviors like hyperactivity or addiction to food starvation and therefore a greater depletion in energy reserves. The question of a transient insensitivity to ghrelin and/or a potential metabolic reprograming is discussed in regard of new clinical treatments currently investigated. PMID:23549309

  2. The activity of gastric ghrelin positive cells in obese patients treated surgically.

    Directory of Open Access Journals (Sweden)

    Artur Bossowski

    2009-12-01

    Full Text Available Ghrelin is a 28 amino acid peptide hormone regulating food intake and stimulating releasement of growth hormone. It is produced in a distinct endocrine call known as X/A - like cells. The most abundant source of this very important factor in energy homeostasis is gastric fundus. Regulatory mechanisms of ghrelin synthesis and secretion in physiological and pathological states are not discovered completely. The aim of our study was evaluation of the activity of gastric X/A-like cells in obese patients before and after the most popular surgical bariatric procedures - Roux - Y Gastric Bypass (RYGB and Laparoscopic Adjustable Gastric Banding (LAGB. Obese patients in number 18 took part in the study. LAGB was performed in 7 patients and RYGB in 11 patients. Peripheral blood was taken from each patient before operation and first day, seventh day, one month and three months after surgery. Ghrelin level was determined by RIA technique. The specimen of stomach was taken from circular stapler after gastrojejunostomy during RYGB and immunohistochemical study of gastric mucosa, using the EnVision method and specific monoclonal antybodies against ghrelin was performed. The intensity of ghrelin-immunoreactivity in X/A-like cells was analyzed using Olympus Cell D image analysis system. Efficiency of bariatric procedures was estimated by EWL- excess weight loss. We observed very strong immunohistochemical reactions of gastric X/A-like cells, accompanied by lower ghrelin plasma concentration, in comparison to the control group. LAGB procedure induced increase of ghrelin plasma level while RYGB procedure induced decrease of this hormone. The main finding of the present study is the hypoactivity of gastric X/A-like cells in obese patients in comparison to the control group.

  3. Oral and transdermal estrogens both lower plasma total homocysteine in male-to-female transsexuals

    NARCIS (Netherlands)

    Giltay, E.J.; Verhoef, P.; Gooren, L.J.G.; Geleijnse, J.M.; Schouten, E.G.; Stehouwer, C.D.A.

    2003-01-01

    Plasma total homocysteine (tHcy) levels are on average lower in women versus men, indicating an estrogenic effect. Oral estrogens (absorbed via the liver) may be hypothesized to have stronger effects on hepatic homocysteine metabolism than transdermal estrogens. We randomly assigned 30 male-to-femal

  4. Ghrelin is independently associated with anti-mullerian hormone levels in obese but not non-obese women with polycystic ovary syndrome.

    Science.gov (United States)

    Garin, Margaret C; Butts, Samantha F; Sarwer, David B; Allison, Kelly C; Senapati, Suneeta; Dokras, Anuja

    2017-03-01

    Ghrelin is an endogenous appetite stimulant that may have a role in ovarian function. Women with polycystic ovary syndrome have anovulation and frequently weight management issues; however the associations between ghrelin and hormonal markers in polycystic ovary syndrome have not been well studied. In order to characterize the association between total ghrelin levels and ovarian function and the possible modification of this relationship by obesity, we examined total ghrelin levels and anti-mullerian hormone, total testosterone, and insulin in obese and non-obese women with and without polycystic ovary syndrome. Total ghrelin levels were lower in obese women with polycystic ovary syndrome (n = 45) compared to obese controls (n = 33) (p = 0.005), but similar in non-obese women with polycystic ovary syndrome (n = 20) compared to non-obese controls (n = 21) (p = NS). In the obese polycystic ovary syndrome group, anti-mullerian hormone was associated with ghrelin levels independent of age, insulin, and total testosterone (p = 0.008). There was no association between total ghrelin and anti-mullerian hormone levels in non-obese women with polycystic ovary syndrome, non-obese controls, or obese controls (p = NS). Our results provide evidence for a potential relationship between ghrelin and ovarian function in obese women with polycystic ovary syndrome that was not observed in non-obese women with polycystic ovary syndrome or controls.

  5. Metabolic and Cardiovascular Effects of Ghrelin

    Science.gov (United States)

    Tesauro, Manfredi; Schinzari, Francesca; Caramanti, Miriam; Lauro, Renato; Cardillo, Carmine

    2010-01-01

    Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is synthesized as a preprohormone and then proteolytically processed to yield a 28-amino acid peptide. This peptide was originally reported to induce growth hormone release; large evidence, however, has indicated many other physiological activities of ghrelin, including regulation of food intake and energy balance, as well as of lipid and glucose metabolism. Ghrelin receptors have been detected in the hypothalamus and the pituitary, but also in the cardiovascular system, where ghrelin exerts beneficial hemodynamic activities. Ghrelin administration acutely improves endothelial dysfunction by increasing nitric oxide bioavailability and normalizes the altered balance between endothelin-1 and nitric oxide within the vasculature of patients with metabolic syndrome. Other cardiovascular effects of ghrelin include improvement of left ventricular contractility and cardiac output, as well as reduction of arterial pressure and systemic vascular resistance. In addition, antinflammatory and antiapoptotic actions of ghrelin have been reported both in vivo and in vitro. This review summarizes the most recent findings on the metabolic and cardiovascular effects of ghrelin through GH-dependent and -independent mechanisms and the possible role of ghrelin as a therapeutic molecule for treating cardiovascular diseases. PMID:20798901

  6. Ghrelin and motilin in the gastrointestinal system.

    Science.gov (United States)

    Chen, Chih-Yen; Tsai, Chang-Youh

    2012-01-01

    Human ghrelin and human motilin, belonging to the ghrelin/motilin-related peptide family, share 36% amino acid sequence identity, while the human ghrelin receptor exhibits a remarkable 50% overall identity with the human motilin receptor. In addition to their structural resemblance, ghrelin and motilin are the only two mammalian hormones known to decrease in the postprandial period. Ghrelin and motilin participate in initiating the migrating motor complex in the stomach, and stimulate gastrointestinal motility, accelerate gastric emptying, and induce "gastric hunger". In addition to modulating the release of growth hormone and gut motility, ghrelin plays a crucial role in the secretion and protection of the stomach and colon. Ghrelin mimetics and motilin agonists are currently being developed to reverse gastrointestinal hypomotility disorders. With additional appetite-enhancing, adiposity-promoting, and anti-inflammatory effects, ghrelin and rikkunshito (a traditional Japanese herb enhancing acyl ghrelin signaling) are superior to motilin in the treatment of cancer-related anorexia and cachexia, post-chemotherapy symptoms, rheumatological diseases, age-related frailty, as well as post-operative, septic, and post-burn gut ileus.

  7. Ghrelin Suppression and Fat Loss after Left Gastric Artery Embolization in Canine Model

    Energy Technology Data Exchange (ETDEWEB)

    Bawudun, Dilmurat [Xinjiang Medical University, Department of Interventional Radiology, First Affiliated Hospital (China); Xing Yan; Liu Wenya, E-mail: wenyaliu2002@hotmail.com; Huang Yujie [Xinjiang Medical University, Imaging Center, First Affiliated Hospital (China); Ren Weixin [Xinjiang Medical University, Department of Interventional Radiology, First Affiliated Hospital (China); Ma Mei [Xinjiang Medical University, Animal Research Center, First Affiliated Hospital (China); Xu Xiaodong [Xinjiang Medical University, Department of Interventional Radiology, First Affiliated Hospital (China); Teng Gaojun [Southeast University, Department of Radiology, Zhong-da Hospital (China)

    2012-12-15

    Purpose: To evaluate the effects of left gastric artery embolization (LGAE) on plasma ghrelin levels, abdominal fat, and body weight in beagles. Methods: The institutional animal care and use committee approved this study. Fifteen healthy adult beagles (12 male and three female animals) were randomly divided into three experimental groups: LGAE was proceeded with mixed emulsion of bleomycin A{sub 5} hydrochloride and lipiodol (group A), and polyvinyl alcohol particles (group B). Transcatheter saline injections in the left gastric artery were performed as a control. Weight and fasting plasma ghrelin levels were obtained at baseline and at weekly intervals for 8 weeks after the procedure in all animals. All animals were scanned and measured by multidetector computed tomography at baseline and at week 8 for evaluation of abdominal fat. Results: In LGAE-treated animals, plasma ghrelin and body weight significantly decreased compared to control animals (group A: P = 0.007 and P = 0.000; group B: P = 0.004 and P = 0.000, respectively). Subcutaneous fat size was also significantly reduced (P = 0.011 and P = 0.027 for groups A and B, respectively). The decreasing percentage in ghrelin levels at week 6 (peak of recovery) of LGAE-treated animals were negatively correlated with the size of area supplied by left gastric artery (r = -0.693, P = 0.026). Conclusion: LGAE could suppress the plasma concentration of ghrelin, which results in subcutaneous fat size reduction and weight loss. Compensatory ghrelin production might occur in the remnant gastric fundus after LGAE.

  8. The Effect of Endurance Training on Ghrelin, Insulin, Glucose and Estrogen in Male Rats

    Directory of Open Access Journals (Sweden)

    Abbas Ghanbari-Niaki

    2014-02-01

    Full Text Available Background: Ghrelin is a 28-amino-acid peptide hormone that is secreted primarily by stomach cells with lesser amounts secreted by other cells (including the hypothalamus. The aim of present study was to examine the effects of 8 weeks aerobic training with different durations on resting plasma Ghrelin levels in male rats. Materials and Methods: Fifty adult Wistar male rats (6-8 weeks old, 270±10 g were selected and randomly divided into five groups: 30, 60 and 90 min training, sham and control groups. All experimental groups performed an 8-week treadmill running program at the same velocity at 0 gradients for 30, 60 or 90 min/day, 5 days/week. The concentration of ghrelin in blood samples was assessed after 8 weeks and 72 hours following the final training session. The ghrelin concentration was measured by ELISA. Possible statistically significant differences between groups after the exercise training intervention was determined by one way ANOVA, and LSD test was used for a post hoc analysis. Results: Resting levels of ghrelin concentration were unchanged after training. Similarly, there was no observed change in the insulin and glucose concentrations compared with the control group. However there was a significant difference in estrogen when compared with the control group. Conclusion: The data suggest that body weight reduction is amplified by exercise-induced and increases in plasma estradiol and a moderate duration exercise program.

  9. Dynamic monitoring of total plasma homocysteine in spontaneously hypertensive rats by LC-MS.

    Science.gov (United States)

    Hu, Lu-Feng; Li, Jun-Wei; Wang, Xian-Qin; Xu, Ren-Ai; Xu, Xue-Gu; Jiang, Hai-Yan; Zhang, Xiu-Hua

    2010-10-01

    Hypertension has been recognized to be closely related to plasma homocysteine levels (tHcy). Spontaneously hypertensive rats (SHR) are used widely for hypertension research, but it is unclear whether hypertension is related to high levels of tHcy in rat plasma. To test whether hyperhomocysteinemia occurs in SHR we dynamically measured plasma total homocysteine (tHcy) in SHR by liquid chromatography-tandem mass spectrometry (LC-MS). This analytical method has good linearity within the range of 1-100 micromol/L for tHcy in rat plasma with a correlation coefficient of R = 0.9975. After dynamic monitoring (12 weeks) on the plasma tHcy in SHR and Wistar-Kyoto rats, we found that there was no significant difference in tHcy level between SHR and Wistar-Kyoto rats, which was 6.98 +/- 1.82 micromol/L and 8.04 +/- 1.64 micromol/L, respectively. And there was no significantly high level of plasma tHcy in SHR.

  10. Growth hormone, ghrelin and peptide YY secretion after oral glucose administration in healthy and obese women.

    Science.gov (United States)

    Outeiriño-Blanco, E; Garcia-Buela, J; Sangiao-Alvarellos, S; Pertega-Diaz, S; Martinez-Ramonde, T; Cordido, F

    2011-07-01

    The mechanism of the altered GH secretion in obesity is unclear. There is evidence that oral glucose (OG) administration initially decreases and subsequently stimulates GH secretion. Ghrelin is a peptide that displays strong growth hormone-releasing activity. Its physiological importance on GH regulation is unclear. Our aim was to study fasting GH concentrations and their response to OG administration in relation with ghrelin secretion in obese and healthy women, in order to elucidate the hypothetical participation of ghrelin on post-oral glucose GH secretion. 36 women were included in the study. After an overnight fast, 75 g of oral glucose was administered; glucose, insulin, ghrelin, and PYY (1-36) were obtained at baseline and during 300 min. The area under the curve between 0 and 300 min (AUC) of GH μ/l·min) was lower in obese patients than in controls; 262.5±57.5 vs. 534.9±95.6, p=0.01, for obese and controls respectively. GH peak (μg/l) was lower in obese patients than in controls; 3.7±0.7 vs. 7.1±1.0, p=0.012, for obese and controls, respectively. The AUC of total ghrelin (pg/ml·min) was lower in obese patients than in controls; 233,032±12,641 vs. 333,697±29,877, p=0.004, for the obese patients and controls respectively. PYY (1-36) was similar in obese and healthy women after OG. There were significant correlations between the different indices of post-oral glucose GH and ghrelin secretion. These data suggest that ghrelin is a physiological regulator of GH in the post-oral glucose state, and the decreased ghrelin secretion could be one of the mechanisms responsible for the altered GH secretion in obesity.

  11. Ghrelin improves intestinal mucosal atrophy during parenteral nutrition: An experimental study.

    Science.gov (United States)

    Yamada, Waka; Kaji, Tatsuru; Onishi, Shun; Nakame, Kazuhiko; Yamada, Koji; Kawano, Takafumi; Mukai, Motoi; Souda, Masakazu; Yoshioka, Takako; Tanimoto, Akihide; Ieiri, Satoshi

    2016-12-01

    Total parenteral nutrition (TPN) has been reported to be associated with mucosal atrophy of the small intestine. Ghrelin has hormonal, orexigenic, and metabolic activities. We investigated whether ghrelin improved intestinal mucosal atrophy using a TPN-supported rat model. Rats underwent jugular vein catheterization and were divided into four groups: TPN alone (TPN), TPN plus low-dose ghrelin (TPNLG), TPN plus high-dose ghrelin (TPNHG), and oral feeding with normal chow (OF). Ghrelin was administered continuously at dosages of 10 or 50 μg/kg/day. On day 6 rats were euthanized, and the small intestine was harvested and divided into the jejunum and ileum. Then the villus height (VH) and crypt depth (CD) were evaluated. The jejunal and ileal VH and CD in the TPN group were significantly decreased compared with those in the OF group. TPNHG improved only VH of the jejunum. TPNLG improved VH and CD of the jejunum and CD of the ileum. The improvement of TPNLG was significantly stronger than that in CD of the jejunum and ileum. TPN was more strongly associated with mucosal atrophy in the jejunum than in the ileum. Low-dose intravenous administration of ghrelin improved TPN-associated intestinal mucosal atrophy more effectively than high-dose administration. Copyright © 2016. Published by Elsevier Inc.

  12. Role of duodenum in regulation of plasma ghrelin level and body mass index after subtotal gastrectomy%胃次全切除术后十二指肠调节血浆ghrelin水平及人体质量指数的作用

    Institute of Scientific and Technical Information of China (English)

    王海涛; 卢麒丞; 王勃; 王荣朝; 张云; 陈海龙; 钱海鑫

    2008-01-01

    目的 研究胃次全切除术后十二指肠调节血浆ghrelin水平与人体质量指数(BMI)的作用.探讨ghrelin与BMI之间的关系.方法 选择42例行胃癌根治手术的T1-2N0-1M0胃癌患者,根据消化道重建方式分为毕Ⅰ式组(23例)和毕Ⅱ式组(19例).分别测定患者术前、术后第1、7、30和360天的血浆ghrelin水平及BMI.结果 两组患者术后早期ghrlein水平下降幅度基本一致:第1天下降至最低(36.7%比35.7%).第7天均有所回升(51.0%比51.1%),两组差异无统计学意义(P>0.05).第30天,两组ghrelin水平分别恢复至70.6%和67.2%,毕Ⅰ式组较毕Ⅱ式组有增高趋势.第360天时,毕Ⅰ式组ghrelin水平恢复至93.1%,虽低于术前水平、但差异无统计学意义(P>0.05);而毕Ⅱ式组仅恢复至81.6%,明显低于术前水平(P=0.033);两组ghrelin水平差异有统计学意义(P=0.035).与术前相比,两组患者ghrelin水平在术后360天分别下降6.9%和18.4%;BMI下降3.3%和6.4%.ghrelin和BMI下降幅度之间两组均存在着线性关系(R12=0.297,P=0.007;R22=0.559,P<0.01).结论 符合解剖生理的十二指肠能代偿性地促进术后患者血浆ghrelin水平的恢复,相应地促进BMI的恢复.ghrelin分泌不足的患者ghrelin水平与BMI呈正相关.%Objective To investigate the role of duodenum in regulation of ghrelin and body mass index (BMI) and the correlation between ghrelin and BMI after subtotal gastrectomy.Methods Forty-two patients with T0-1N0-1M0 gastric cancer were divided into two groups after gastrectomy according to digestive reconstruction pattern,Bi]lroth Ⅰ group (n=23) and Billroth Ⅱ group (n=19) respectively.Plasma ghrelin levels were determined by radioimmunoassay (RIA) before and at day 1, 7, 30 and 360 after gastreetomy,and BMIs were also measured. Results Two groups had identical postoperative trends in ghrelin alterations during the early stage, both dropping to nadir at day 1 (36.7% vs 35.7%), then markedly increasing at day 7

  13. Comparison of the effects of growth hormone on acylated ghrelin and following acute intermittent exercise in two levels of obesity

    Directory of Open Access Journals (Sweden)

    Majid Gholipour

    2013-08-01

    Full Text Available Background: The prevalence of obesity has risen enormously over the past few decad-es. Both food intake (Appetite and energy expenditure can influence body weight. Acylated ghrelin enhances appetite, and its plasma level is suppressed by growth horm-one. The present study, examines the effects of an intermittent exercise with progress-ive intensities on acylated ghrelin, appetite, and growth hormone in inactive male students with two levels of obesity.Methods: Eleven inactive males were allocated into two groups on the basis of their body mass index (BMI. Six subjects in group one, BMI= 31.18±0.92 kg/m2, and five subjects in group two, BMI= 36.94±2.25 kg/m2, ran on the treadmill with progressive intensities of 50, 60, 70 and 80% of VO2max for 10, 10, 5, and 2 min respectively. Blood samples were collected before the exercise (as the resting values, after each workload (during the exercise, and at 30, 60, and 120 min (during recovery.Results: Plasma acylated ghrelin concentrations and hunger ratings in two groups were decreased and remained significantly lower than resting values (P=0.008 and P=0.002 respectively at the end of the trial and there was no significant differences between groups. Growth hormone levels in two groups were increased and remained significant-ly higher than resting values (groups one P=0.012, group two P=0.005 at the end of the trial and there was no significant differences between groups. In addition, there were no significant differences between area under the curves (AUC values over total periods for acylated ghrelin, hunger ratings, and growth hormone in two groups.Conclusion: These findings indicate that individuals with two levels of obesity have the same response to the different intensities of treadmill running and two hours thereafter during recovery period, which can be considered for designing a more effective weighting loss training program.

  14. Plasma total thiol pool in children with asthma: Modulation during montelukast monotherapy.

    Science.gov (United States)

    Dilek, Fatih; Ozkaya, Emin; Kocyigit, Abdurrahim; Yazici, Mebrure; Guler, Eray Metin; Dundaroz, Mehmet Rusen

    2016-03-01

    Inflammation, which is a hallmark of asthma, is one of the main sources of oxidative stress in the human body. Thiols are powerful antioxidants that protect cells against the consequences of oxidative stress. We aimed to investigate whether asthma and montelukast monotherapy affect the total plasma thiol pool in children. A total of 60 children with asthma and 35 healthy controls participated in the study. Group I consisted of newly diagnosed asthmatics who did not have regular anti-asthmatic therapy previously. Group II consisted of patients who had been undertaking montelukast monotherapy regularly for at least 4 months. Plasma total antioxidant status (TAS) and plasma total thiol (PTT) were measured using spectrophotometric methods. Bronchial asthma patients in both groups I and II had decreased median TAS levels compared with the control group (1.59 [interquartile range, 1.04-1.70] and 1.67 [1.50-1.75] vs. 2.98 [2.76-3.16] Trolox equiv./L, respectively; P0.05). In addition, the median TAS and PTT levels for groups I and II were not statistically different (P>0.05). There was a positive correlation between TAS and PTT levels (rho=0.38, Pchildren with asthma. Montelukast monotherapy can limit oxidative stress and thus restore PTT levels but not TAS levels in asthmatic children. © The Author(s) 2015.

  15. 血浆生长素释放肽水平与阻塞性睡眠呼吸暂停及冠心病的关系%The Relationship Between Plasma Ghrelin Levels,Obstructive Sleep Apnea and Coronary Heart Disease

    Institute of Scientific and Technical Information of China (English)

    杨丹

    2011-01-01

    More research is showing that sleep apnea is an independent risk factor for coronary heart diseases (CHD) , and is associated with CHD mortality rates. Obesity is the common risk factor for both obstructive sleep apnea and CHD. Growth hormone releasing pep-tide (ghrelin) stimulates appetite , facilitates fat storage, and may interact with pulmonary and cardiovascular function. This review examines the relationship between plasma ghrelin levels, obesity, and the pathophysiological process of obstructive sleep apnea and coronary heart disease.%越来越多的研究表明阻塞性睡眠呼吸暂停是冠心病发病的独立危险因素,与冠心病的病死率有关联.肥胖是二者的共有危险因素;生长素释放肽是一种新型的脑肠肽,能影响食欲和能量平衡,导致肥胖;目前还发现其对呼吸节律、肺功能、心血管组织均产生影响.为了进一步了解血浆生长素释放肽水平与阻塞性睡眠呼吸暂停、冠心病发生发展的病理生理过程,作一相关综述.

  16. Treatment of TBI and Concomitant Hemorrhage with Ghrelin

    Science.gov (United States)

    2010-07-01

    battlefield setting. 15. SUBJECT TERMS Traumatic brain injury ; hemorrhagic shock; ghrelin; treatment 16. SECURITY CLASSIFICATION OF: U 17...hemorrhagic shock. 2. Ghrelin treatment improves sensorimotor and reflex function after traumatic brain injury and uncontrolled hemorrhagic shock...3. Ghrelin treatment reduces cortical apoptosis after traumatic brain injury and uncontrolled hemorrhagic shock. 4. Ghrelin treatment

  17. Plasma Total Antioxidant Capacity and Cardiometabolic Risk in Non-Obese and Clinically Healthy Young Adults.

    Science.gov (United States)

    Costa, Jamille Oliveira; Vásquez, Cecília M Passos; Santana, Gleiciane de Jesus; Silva, Natanael de Jesus; Braz, Juciene de Matos; Jesus, Amélia M Ribeiro de; Silva, Danielle Góes da; Cunha, Luana Celina Seraphim; Barbosa, Kiriaque Barra Ferreira

    2017-07-10

    The oxidative biomarkers play an important role in the genesis of cardiometabolic risk-related processes. To investigate the total antioxidant capacity of plasma and its association with cardiometabolic risk in non-obese and clinically healthy young adults. University students of the state of Sergipe, Brazil, aged between 18 and 25 years, were recruited for this study from May of 2013 and October of 2014. Anthropometric, clinical and biochemical parameters were measured and analyzed using protocols which were previously standardized and described in the literature. The measurement of plasma total antioxidant capacity was based on the ability that all the antioxidants present in the sample (plasma) have to inhibit the oxidation of the oxidizable substrate ABTS (2,2`- Azino-di-[3-ethylbenzthiazoline sulphonate]) to ABTS•+ by metmyoglobin. Approximately 25% of the sample presented more than one component of cardiometabolic risk. Low HDL-cholesterol was the most prevalent component. Compared to absence of components, the subjects with at least one component presented greater body weight and waist circumference, higher levels of diastolic blood pressure and fasting glucose, greater total cholesterol/HDL-c ratio, and lower levels of HDL-c (p literatura. A medida da capacidade antioxidante total do plasma baseou-se na capacidade de todos os antioxidantes presentes na amostra (plasma) em inibir a oxidação do substrato oxidável ABTS (2,2-Azino-bis-(3-etilbenzotiazolina-6-sulfonato) a ABTS•+ pela metamioglobina. Aproximadamente 25% da amostra apresentaram mais de um componente do risco cardiometabólico. Valores baixos de HDL foram o componente mais prevalente. Em comparação à ausência de componentes, os indivíduos com pelo menos um componente apresentou valores mais altos de peso corporal, circunferência da cintura, pressão sanguínea diastólica, glicemia de jejum e razão colesterol total/HDL-c, e valores mais baixos de HDL-c (p < 0,05). A glicemia de jejum

  18. Potentiation of ghrelin signaling attenuates cancer anorexia-cachexia and prolongs survival.

    Science.gov (United States)

    Fujitsuka, N; Asakawa, A; Uezono, Y; Minami, K; Yamaguchi, T; Niijima, A; Yada, T; Maejima, Y; Sedbazar, U; Sakai, T; Hattori, T; Kase, Y; Inui, A

    2011-07-26

    Cancer anorexia-cachexia syndrome is characterized by decreased food intake, weight loss, muscle tissue wasting and psychological distress, and this syndrome is a major source of increased morbidity and mortality in cancer patients. This study aimed to clarify the gut-brain peptides involved in the pathogenesis of the syndrome and determine effective treatment for cancer anorexia-cachexia. We show that both ghrelin insufficiency and resistance were observed in tumor-bearing rats. Corticotropin-releasing factor (CRF) decreased the plasma level of acyl ghrelin, and its receptor antagonist, α-helical CRF, increased food intake of these rats. The serotonin 2c receptor (5-HT2cR) antagonist SB242084 decreased hypothalamic CRF level and improved anorexia, gastrointestinal (GI) dysmotility and body weight loss. The ghrelin receptor antagonist (D-Lys3)-GHRP-6 worsened anorexia and hastened death in tumor-bearing rats. Ghrelin attenuated anorexia-cachexia in the short term, but failed to prolong survival, as did SB242084 administration. In addition, the herbal medicine rikkunshito improved anorexia, GI dysmotility, muscle wasting, and anxiety-related behavior and prolonged survival in animals and patients with cancer. The appetite-stimulating effect of rikkunshito was blocked by (D-Lys3)-GHRP-6. Active components of rikkunshito, hesperidin and atractylodin, potentiated ghrelin secretion and receptor signaling, respectively, and atractylodin prolonged survival in tumor-bearing rats. Our study demonstrates that the integrated mechanism underlying cancer anorexia-cachexia involves lowered ghrelin signaling due to excessive hypothalamic interactions of 5-HT with CRF through the 5-HT2cR. Potentiation of ghrelin receptor signaling may be an attractive treatment for anorexia, muscle wasting and prolong survival in patients with cancer anorexia-cachexia.

  19. Potentiation of ghrelin signaling attenuates cancer anorexia–cachexia and prolongs survival

    Science.gov (United States)

    Fujitsuka, N; Asakawa, A; Uezono, Y; Minami, K; Yamaguchi, T; Niijima, A; Yada, T; Maejima, Y; Sedbazar, U; Sakai, T; Hattori, T; Kase, Y; Inui, A

    2011-01-01

    Cancer anorexia–cachexia syndrome is characterized by decreased food intake, weight loss, muscle tissue wasting and psychological distress, and this syndrome is a major source of increased morbidity and mortality in cancer patients. This study aimed to clarify the gut–brain peptides involved in the pathogenesis of the syndrome and determine effective treatment for cancer anorexia–cachexia. We show that both ghrelin insufficiency and resistance were observed in tumor-bearing rats. Corticotropin-releasing factor (CRF) decreased the plasma level of acyl ghrelin, and its receptor antagonist, α-helical CRF, increased food intake of these rats. The serotonin 2c receptor (5-HT2cR) antagonist SB242084 decreased hypothalamic CRF level and improved anorexia, gastrointestinal (GI) dysmotility and body weight loss. The ghrelin receptor antagonist (D-Lys3)-GHRP-6 worsened anorexia and hastened death in tumor-bearing rats. Ghrelin attenuated anorexia–cachexia in the short term, but failed to prolong survival, as did SB242084 administration. In addition, the herbal medicine rikkunshito improved anorexia, GI dysmotility, muscle wasting, and anxiety-related behavior and prolonged survival in animals and patients with cancer. The appetite-stimulating effect of rikkunshito was blocked by (D-Lys3)-GHRP-6. Active components of rikkunshito, hesperidin and atractylodin, potentiated ghrelin secretion and receptor signaling, respectively, and atractylodin prolonged survival in tumor-bearing rats. Our study demonstrates that the integrated mechanism underlying cancer anorexia–cachexia involves lowered ghrelin signaling due to excessive hypothalamic interactions of 5-HT with CRF through the 5-HT2cR. Potentiation of ghrelin receptor signaling may be an attractive treatment for anorexia, muscle wasting and prolong survival in patients with cancer anorexia–cachexia. PMID:22832525

  20. Relationship between Serum Leptin, Ghrelin and Dietary Macronutrients in Women with Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Bahram Pourghassem Gargari

    2015-10-01

    Full Text Available Background: Polycystic ovary syndrome (PCOS is the most common endocrinopathy in women. It may involve an impairment in physiologic regulation of leptin and ghrelin. There is limited, controversial data on the relation of dietary components with leptin and ghrelin in PCOS, so the current study has been conducted to explore the effects of different macronutrients on serum levels of leptin and ghrelin in PCOS and healthy subjects. Materials and Methods: In this case-control study, we randomly choose 30 PCOS patients and 30 healthy age and body mass index (BMI matched controls. Intake of macronutrients [protein, total fat, saturated, monounsaturated and polyunsaturated fatty acids (PUFA, carbohydrate, dietary fiber] and energy were assessed using 3-day, 24-hour food recall and food frequency questionnaires (FFQ. Fasting hormonal status was measured for each participant. Results: PCOS women had higher levels of serum leptin, insulin, testosterone, and luteinizing hormone (LH, whereas sex hormone-binding globulin (SHBG was lower compared to healthy women. There was no significant difference in mean ghrelin concentrations between the groups. Among PCOS women, independent of BMI and total energy intake, we observed an inverse association between leptin concentration and total dietary fat (β=-0.16, P<0.05 and saturated fatty acid (SFA intake (β=-0.58, P<0.05. This relationship was not seen in the healthy subjects. There was no significant association between ghrelin and macronutrients in PCOS and healthy participants. Conclusion: Certain habitual dietary components such as fat and SFA may decrease serum leptin, whereas ghrelin is not influenced by these in PCOS women. More studies are needed to better clarify the effects of dietary macronutrients on serum leptin and ghrelin.

  1. Effects of glucagon on plasma ghrelin level in type 2 diabetes mellitus%胰高血糖素对2型糖尿病病人血浆生长激素释放肽的影响

    Institute of Scientific and Technical Information of China (English)

    林少达; 陈仲贤; 林楚佳; 段红艳

    2009-01-01

    Objective To investigate the effect of glucagon on ghrelin seretion in type 2 diabetes mellitus(T2DM)patients.Methods Circulating ghrelin and C-pepetide were measured during glucagon stimulation test in 38 cases with T2DM and 30 cases in normal controls(NC)at the 1st Affiliated Hospital of Shantou University from May 2006 to December 2007.Results(1)There w88 no significant difference in the fasting C-peptide and fasting ghrelin levels of the NC group were(1.3±0.6)μg/L and(3.0±1.0)ng/ml respectively,both not significantly different from those of the T2DM group[(1.2±0.4)μg/L and (2.7±0.8)μg/L respectively,P>0.05 and P>0.05];six minutes after the injection of glucagon,the C-peptide level of the T2DM group increased to(2.0±0.8)μg/L(P0.05).(2)Fasting ghrelin level was significantly negatively correlated with the waist circumference(r=0.343,P0.05);(2)空腹血浆ghrelin水平与腰围呈负相关(r=0.343,P<0.01),是它的独立预测因子.结论 ghrelin分泌可能与T2DM病人胰岛β细胞功能减退及早相胰岛素分泌缺陷有关;胰岛素、胰高血糖素及ghrelin可能相瓦作用影响糖调节.

  2. Acetylcholine regulates ghrelin secretion in humans

    NARCIS (Netherlands)

    F. Broglio (Fabio); E. Ghigo (Ezio); C. Gottero; F. Prodam (Flavia); S. Destefanis; A. Benso; C. Gauna (Carlotta); L.J. Hofland (Leo); E. Arvat; A-J. van der Lely (Aart-Jan); P.M. van Koetsveld (Peter)

    2004-01-01

    textabstractGhrelin secretion has been reportedly increased by fasting and energy restriction but decreased by food intake, glucose, insulin, and somatostatin. However, its regulation is still far from clarified. The cholinergic system mediates some ghrelin actions, e.g. stimulatio

  3. Ghrelin- and GH-induced insulin resistance

    DEFF Research Database (Denmark)

    Vestergaard, Esben Thyssen; Krag, Morten B; Poulsen, Morten M

    2013-01-01

    Supraphysiological levels of ghrelin and GH induce insulin resistance. Serum levels of retinol-binding protein-4 (RBP4) correlate inversely with insulin sensitivity in patients with type 2 diabetes. We aimed to determine whether ghrelin and GH affect RBP4 levels in human subjects....

  4. Acute Exercise Increases Plasma Total Antioxidant Status and Antioxidant Enzyme Activities in Untrained Men

    OpenAIRE

    Berzosa, C.; I. Cebrián; Fuentes-Broto, L.; E. Gómez-Trullén; Piedrafita, E.; Martínez-Ballarín, E.; López-Pingarrón, L.; Reiter, R. J.; García, J. J.

    2011-01-01

    Antioxidant defences are essential for cellular redox regulation. Since free-radical production may be enhanced by physical activity, herein, we evaluated the effect of acute exercise on total antioxidant status (TAS) and the plasma activities of catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase and its possible relation to oxidative stress resulting from exercise. Healthy untrained male subjects ( = 3 4 ) performed three cycloergometric tests, including maxi...

  5. Effects of total gastrectomy on plasma silicon and amino acid concentrations in men.

    Science.gov (United States)

    Tatara, Marcin R; Krupski, Witold; Szpetnar, Maria; Dąbrowski, Andrzej; Bury, Paweł; Szabelska, Anna; Charuta, Anna; Boguszewska-Czubara, Anna; Maciejewski, Ryszard; Wallner, Grzegorz

    2015-12-01

    The aim of the study was to determine one-year effects of total gastrectomy on plasma silicon and free amino acid concentrations in patients and evaluate changes of volumetric bone mineral density (vBMD) in lumbar spine. Eight patients were enrolled to the control (CTR) group. Six patients subjected to total gastrectomy (GX group) were included to the experimental group. vBMD in trabecular and cortical bone was measured in lumbar vertebrae at baseline (before surgery) and one year later using quantitative computed tomography. Plasma concentrations of silicon and free amino acids were determined at baseline and one year later using photometric method and ion-exchange chromatography. Body weights within CTR and GX groups were not different after one-year follow-up when compared to the baseline values (P > 0.05). An average annual decrease of vBMD in the trabecular bone in the gastrectomized patients reached 15.0% in lumbar spine and was significantly different in comparison to the percentage changes observed in CTR group (P = 0.02). One-year percentage change of vBMD in the cortical bone in L1 and L2 has shown significantly decreased values by 10.5 and 9.1% in the GX group when compared to the percentage change observed in the controls (P silicon was significantly lowered by 26.7% one year after the total gastrectomy when compared to the baseline value (P = 0.009). Total gastrectomy in patients has induced severe osteoporotic changes in lumbar spine within one-year period. The observed osteoporotic changes were associated with decreased plasma concentration of silicon indicating importance of exocrine and endocrine functions of stomach for silicon homeostasis maintenance. Gastrectomy-induced bone loss was not related to decreased amino acid concentration in plasma obtained from overnight fasted patients.

  6. Recent Advances in Potential Clinical Application of Ghrelin in Obesity

    Directory of Open Access Journals (Sweden)

    Christine Delporte

    2012-01-01

    Full Text Available Ghrelin is the natural ligand of the growth hormone secretagogue receptor (GHS-R1a. Ghrelin is a 28 amino acid peptide possessing a unique acylation on the serine in position 3 catalyzed by ghrelin O-acyltransferase (GOAT. Ghrelin stimulates growth hormone secretion, but also appetite, food intake, weight gain, and gastric emptying. Ghrelin is involved in weight regulation, obesity, type 2 diabetes, and metabolic syndrome. Furthermore, a better understanding of ghrelin biology led to the identification of molecular targets modulating ghrelin levels and/or its biological effects: GOAT, ghrelin, and GHS-R1a. Furthermore, a recent discovery, showing the involvement of bitter taste receptor T2R in ghrelin secretion and/or synthesis and food intake, suggested that T2R could represent an additional interesting molecular target. Several classes of ghrelin-related pharmacological tools for the treatment of obesity have been or could be developed to modulate the identified molecular targets.

  7. Ghrelin: new molecular pathways modulating appetite and adiposity.

    Science.gov (United States)

    Nogueiras, Ruben; Williams, Lynda M; Dieguez, Carlos

    2010-10-01

    Ghrelin is a unique endogenous peptidic hormone regulating both hunger and adiposity. Many of the actions of ghrelin are modulated specifically by the central nervous system. A number of molecular events triggered via the activation of the ghrelin receptor (GHS-R1a), leading to increased levels of neuropeptide Y (NPY) and agoutirelated peptide (AgRP) and ultimately responsible for the orexigenic effect of ghrelin have been characterized. Moreover, the discovery of ghrelin O-acyltransferase (GOAT), the enzyme responsible for the octanoylation of ghrelin, provides a mechanism allowing specific targeting of the ghrelin/GHS-R1a system without affecting the role of des-acyl-ghrelin in other pathways involved in the regulation of energy balance. This review aims to summarize novel roles of ghrelin in energy balance, focusing particularly on both the newly identified neuronal pathways mediating the effects of ghrelin and on peripheral mechanisms leading to increased adiposity. Copyright © 2010 S. Karger AG, Basel.

  8. High circulating ghrelin: a potential cause for hyperphagia and obesity in prader-willi syndrome

    DEFF Research Database (Denmark)

    DelParigi, Angelo; Tschöp, Matthias; Heiman, Mark L;

    2002-01-01

    of the hyperphagia and abnormal GH secretion are unknown. To determine whether ghrelin, a novel GH secretagogue with orexigenic properties, is elevated in PWS, we measured fasting plasma ghrelin concentration; body composition (dual-energy x-ray absorptiometry); and subjective ratings of hunger (visual analog scale......) in seven subjects (6 males and 1 female; age, 26 +/- 7 yr; body fat, 39 +/- 11%, mean +/- SD) with PWS (diagnosis confirmed by genetic test) and 30 healthy subjects (reference population, 15 males and 15 females; age, 32 +/- 7 yr; body fat, 36 +/- 11%) fasted overnight. All subjects were weight stable...

  9. Ghrelin in Female and Male Reproduction

    Directory of Open Access Journals (Sweden)

    Joëlle Dupont

    2010-01-01

    Full Text Available Ghrelin and one of its functional receptors, GHS-R1a (Growth Hormone Secretagogue Receptor 1a, were firstly studied about 15 years. Ghrelin is a multifunctional peptide hormone that affects several biological functions including food intake, glucose release, cell proliferation… Ghrelin and GHS-R1a are expressed in key cells of both male and female reproductive organs in several species including fishes, birds, and mammals suggesting a well-conserved signal through the evolution and a role in the control of fertility. Ghrelin could be a component of the complex series of nutrient sensors such as adipokines, and nuclear receptors, which regulate reproduction in function of the energy stores. The objective of this paper was to report the available information about the ghrelin system and its role at the level of the hypothalamic-pituitary-gonadal axis in both sexes.

  10. Metabolic and cardiovascular effects of ghrelin

    Directory of Open Access Journals (Sweden)

    E V Kirienkova

    2012-03-01

    Full Text Available Ghrelin is an endogenous ligand for growth hormone receptor, which is synthesized as a prohormone, and then proteolytically converted into 28-amino acid peptide. This peptide stimulates the secretion of growth hormone, regulates food intake, effect on carbohydrate and lipid metabolism. Ghrelin enhances the bioavailability of nitric oxide and maintains the balance between endothelin-1 and nitric oxide in the vascular wall. It increases cardiac output, and reduces blood pressure and systemic vascular resistance. Antiinflammatory effect of ghrelin is also appreciated. Since ghrelin is a circulating peptide that stimulates appetite and regulate energy balance, and its role in the development of obesity and type 2 diabetes it is the subject of intense research. A variety of metabolic functions of ghrelin requires extreme caution in the use of therapeutic approaches aimed at the stimulation or blockade of its action.

  11. Ghrelin in obesity, physiological and pharmacological considerations.

    Science.gov (United States)

    Álvarez-Castro, Paula; Pena, Lara; Cordido, Fernando

    2013-04-01

    The aim of this review is to summarize the physiological and pharmacological aspects of ghrelin. Obesity can be defined as an excess of body fat and is associated with significant disturbances in metabolic and endocrine function. Obesity has become a worldwide epidemic. In obesity there is a decreased growth hormone (GH) secretion, and the altered somatotroph secretion in obesity is functional. Ghrelin is a peptide that has a unique structure with 28 amino-acids and an n-octanoyl ester at its third serine residue, which is essential for its potent stimulatory activity on somatotroph secretion. The pathophysiological mechanism responsible for GH hyposecretion in obesity is probably multifactorial, and there is probably a defect in ghrelin secretion. Ghrelin is the only known circulating orexigenic factor, and has been found to be reduced in obese humans. Ghrelin levels in blood decrease during periods of feeding. Due to its orexigenic and metabolic effects, ghrelin has a potential benefit in antagonizing protein breakdown and weight loss in catabolic conditions such as cancer cachexia, renal and cardiac disease, and age-related frailty. Theoretically ghrelin receptor antagonists could be employed as anti-obesity drugs, blocking the orexigenic signal. By blocking the constitutive receptor activity, inverse agonists of the ghrelin receptor may lower the set-point for hunger, and could be used for the treatment of obesity. In summary, ghrelin secretion is reduced in obesity, and could be partly responsible for GH hyposecretion in obesity, ghrelin antagonist or partial inverse agonists should be considered for the treatment of obesity.

  12. Plasma total homocysteine increases from day 20 to 40 in breastfed but not formula-fed low-birthweight infants

    NARCIS (Netherlands)

    Fokkema, M R; Woltil, H A; van Beusekom, C M; Schaafsma, A; Dijck-Brouwer, D A J; Muskiet, F A J

    2002-01-01

    Homocysteine is an intermediate in the folate cycle and methionine metabolism. This study investigated whether formula-fed infants have different plasma total homocysteine to their breastfed counterparts, and during what period any difference developed. Plasma total homocysteine was determined in 53

  13. RNAi-mediated Ghrelin affects gastric H(+)-K(+)-ATPase activity and expression of GOAT-Ghrelin system in vitro.

    Science.gov (United States)

    Du, Gai M; Wu, Jie G; Luo, Bi P; Hu, Zhi H; Li, Liu A; Liu, Mao J

    2016-03-01

    Ghrelin has been implicated in the regulation of gastric functional development, and its physiological functions are mediated by Ghrelin-O-acyltransferase (GOAT) which is capable of generating the active form of this polypeptide hormone. However, whether and how ghrelin gene silencing may modify gastric acid secretion and GOAT-Ghrelin system is yet to be explored. The study was performed in gastric mucosal cells from weanling piglets in vitro. We evaluated the effect of ghrelin on gastric acid secretion, gene expression of GOAT and ghrelin as well as ghrelin levels by RNA interference assay. shGhrelin triggered the down-regulation of ghrelin mRNA expression (Pghrelin production and secretion (Pghrelin production and secretion were reduced in gastric mucosal cells and culture medium (Pghrelin gene achieved by RNAi-mediation inhibited the activity of H(+)-K(+)-ATPase and pepsin (PGhrelin gene inhibited the gastric acid secretion with decreased GOAT mRNA and acylated Ghrelin in gastric mucosal cells.

  14. Total plasma proANP increases with atrial dilatation in horses.

    Science.gov (United States)

    Van Der Vekens, N; Hunter, I; Timm, A; Decloedt, A; De Clercq, D; Deprez, P; Goetze, J P; van Loon, G

    2015-12-19

    Equine atrial natriuretic peptide (ANP) plasma concentrations are correlated with left atrial size. However, species-specific assays are lacking and the results from human assays are poorly reproducible. A new methodology called processing independent analysis (PIA) that measures the total proANP product in plasma has proven to be successful in human medicine, but has never been used in horses. The aims were to establish an equine proANP reference interval by measurement of the total proANP product using PIA and to examine the proANP concentrations in horses with atrial dilatation. Sample stability was studied by comparison of storage at -80°C and -20°C. Plasma samples were obtained from 23 healthy horses, 12 horses with moderate or severe valvular regurgitation without atrial dilatation and 42 horses with valvular regurgitation and atrial dilatation. The proANP concentration was significantly (Phorses with atrial dilatation (761.4 (442.1-1859.1) pmol/l) than in healthy horses (491.6 (429.5-765.9) pmol/l; Phorses with cardiac disease but without atrial dilatation (544.4 (457.0-677.6) pmol/l). A cut-off value (573.8 pmol/l) for detection of atrial dilatation was calculated. Sample storage at -80°C did not differ from sample storage at -20°C. The measurement of total proANP in plasma detects atrial dilatation in horses and may be useful for clinical evaluation in equine medicine.

  15. Determination of total plasma hydroperoxides using a diphenyl-1-pyrenylphosphine fluorescent probe.

    Science.gov (United States)

    Santas, Jonathan; Guardiola, Francesc; Rafecas, Magda; Bou, Ricard

    2013-03-01

    Plasma hydroperoxides (HPs) are widely accepted to be good indicators of oxidative stress. By means of the method proposed here, which uses diphenyl-1-pyrenylphosphine (DPPP) as a fluorescent probe, all types of plasma HP were determined. The limits of detection and quantification of the method were 0.08 and 0.25 nmol of cumene hydroperoxide (CHP) equivalents in 40 μl of plasma, respectively. The method is satisfactory in terms of precision (5.3% for 14.5 μM CHP eq., n=8), and the recoveries were 91% and 92% after standard additions of 26 and 52 μM CHP, respectively. The selectivity of the proposed method is higher than 96%. Moreover, optimization of the reaction conditions and the addition of ethylenediaminetetraacetic acid (EDTA) disodium salt and 2,6-di-tert-butyl-4-methylphenol (BHT) prevented the formation of HP artifacts during the analysis. Therefore, the proposed method is useful for simple and quantitative determination of total plasma HPs.

  16. Circadian variation in ghrelin and certain stress hormones in crib-biting horses.

    Science.gov (United States)

    Hemmann, Karin; Raekallio, Marja; Kanerva, Kira; Hänninen, Laura; Pastell, Matti; Palviainen, Mari; Vainio, Outi

    2012-07-01

    Crib-biting is classified as an oral stereotypy, which may be initiated by stress susceptibility, management factors, genetic factors and gastrointestinal irritation. Ghrelin has been identified in the gastric mucosa and is involved in the control of food intake and reward, but its relationship to crib-biting is not yet known. The aim of this study was to examine the concentration and circadian variation of plasma ghrelin, cortisol, adrenocorticotropic hormone (ACTH) and β-endorphin in crib-biting horses and non-crib-biting controls. Plasma samples were collected every second hour for 24h in the daily environment of eight horses with stereotypic crib-biting and eight non-crib-biting controls. The crib-biting horses had significantly higher mean plasma ghrelin concentrations than the control horses. The circadian rhythm of cortisol was evident, indicating that the sampling protocol did not inhibit the circadian regulation in these horses. Crib-biting had no statistically significant effect on cortisol, ACTH or β-endorphin concentrations. The inter-individual variations in β-endorphin and ACTH were higher than the intra-individual differences, which made inter-individual comparisons difficult and complicated the interpretation of results. Further research is therefore needed to determine the relationship between crib-biting and ghrelin concentration.

  17. Effects of solid-phase extraction of plasma in measuring gut metabolic hormones in fasted and fed blood of lean and diet-induced obese rats.

    Science.gov (United States)

    Reidelberger, Roger; Haver, Alvin; Anders, Krista; Apenteng, Bettye; Lanio, Craig

    2016-05-01

    Glucagon-like peptide-1 (GLP-1), peptide YY (3-36) [PYY(3-36)], amylin, ghrelin, insulin, and leptin are thought to act as hormonal signals from periphery to brain to control food intake. Here, we determined the effects of solid-phase extraction of plasma in measuring these hormones in blood of lean and diet-induced obese rats. Individual enzyme-linked immunoassays and a multiplex assay were used to measure active GLP-1, total PYY, active amylin, active ghrelin, insulin, leptin, and total GIP in response to (1) addition of known amounts of the peptides to lean and obese plasma, (2) a large meal in lean and obese rats, and (3) intravenous infusions of anorexigenic doses of GLP-1, PYY(3-36), amylin, and leptin in lean rats. Extraction of lean and obese plasma prior to assays produced consistent recoveries across assays for GLP-1, PYY, amylin, ghrelin, and insulin, reflecting losses inherent to the extraction procedure. Plasma extraction prior to assays generally revealed larger meal-induced changes in plasma GLP-1, PYY, amylin, ghrelin, and insulin in lean and obese rats. Plasma extraction and the multiplex assay were used to compare plasma levels of GLP-1, PYY, and amylin after a large meal with plasma levels produced by IV infusions of anorexigenic doses of GLP-1, PYY(3-36), and amylin. Infusions produced dose-dependent increases in plasma peptide levels, which were well above their postprandial levels. These results do not support the hypothesis that postprandial plasma levels of GLP-1, PYY(3-36), and amylin are sufficient to decrease food intake by an endocrine mechanism.

  18. Acute Exercise Increases Plasma Total Antioxidant Status and Antioxidant Enzyme Activities in Untrained Men

    Directory of Open Access Journals (Sweden)

    C. Berzosa

    2011-01-01

    Full Text Available Antioxidant defences are essential for cellular redox regulation. Since free-radical production may be enhanced by physical activity, herein, we evaluated the effect of acute exercise on total antioxidant status (TAS and the plasma activities of catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase and its possible relation to oxidative stress resulting from exercise. Healthy untrained male subjects (=34 performed three cycloergometric tests, including maximal and submaximal episodes. Venous blood samples were collected before and immediately after each different exercise. TAS and enzyme activities were assessed by spectrophotometry. An increase of the antioxidant enzyme activities in plasma was detected after both maximal and submaximal exercise periods. Moreover, under our experimental conditions, exercise also led to an augmentation of TAS levels. These findings are consistent with the idea that acute exercise may play a beneficial role because of its ability to increase antioxidant defense mechanisms through a redox sensitive pathway.

  19. Postprandial ghrelin response is reduced in patients with Parkinson's disease and idiopathic REM sleep behaviour disorder: a peripheral biomarker for early Parkinson's disease?

    Science.gov (United States)

    Unger, Marcus M; Möller, Jens C; Mankel, Katharina; Eggert, Karla M; Bohne, Katharina; Bodden, Maren; Stiasny-Kolster, Karin; Kann, Peter H; Mayer, Geert; Tebbe, Johannes J; Oertel, Wolfgang H

    2011-06-01

    Ghrelin, an orexigenic peptide, has multiple functions, which include promoting gastrointestinal motility and influencing higher brain functions. Experimental data suggest that ghrelin has neuroprotective potential in the MPTP mouse model of Parkinson's disease (PD). PD patients show delayed gastric emptying and other symptoms that may relate to disturbed excretion of ghrelin. No data are available on postprandial ghrelin response in patients with PD and idiopathic REM sleep behaviour disorder (iRBD)--a condition considered a putative preclinical stage of PD. We measured fasting and postprandial ghrelin serum concentrations in 20 healthy controls, 39 (including 19 drug-naïve) PD patients and 11 iRBD patients using a commercial radioimmunoassay for total ghrelin. For statistical analysis we employed ANCOVA and post-hoc testing with Bonferroni's method. Controls showed a decrease of mean fasting ghrelin serum concentrations in the early postprandial phase, followed by a recuperation starting 60 min after the test meal and reaching a maximum at 300 min. This recuperation was less pronounced in PD and iRBD; the slope of relative postprandial ghrelin recovery was different between the investigated groups (p = 0.007). Post-hoc testing showed a difference between controls and PD patients (p = 0.002) and between controls and iRBD patients (p = 0.037). The dynamic regulation of ghrelin in response to food intake is partially impaired in subjects at putative preclinical (iRBD) and clinical stages of PD. Reduced ghrelin excretion might increase the vulnerability of nigrostriatal dopaminergic neurons as suggested by animal studies. The impaired ghrelin excretion might qualify as a peripheral biomarker and be of diagnostic or therapeutic value.

  20. Serum levels of ghrelin and obestatin in children with symptoms suggestive of delayed gastric emptying of unclear etiology

    OpenAIRE

    Saliakellis, Efstratios; Karatzas, Nikolaos; Iakovou, Ioannis; Farmaki, Evangelia; Varlamis, Georgios; Fotoulaki, Maria

    2015-01-01

    Background Ghrelin and obestatin are peptides of the gut-brain axis affecting appetite and gastrointestinal motility. Methods We conducted a cross-sectional, case-control study to determine pre- and postprandial serum levels of total ghrelin and obestatin along with gastric emptying scintigraphy in children with symptoms suggestive of delayed gastric emptying time (GET), not attributable to any identifiable cause. Results Twenty children with symptoms suggestive of delayed GET, of whom 9 had ...

  1. Seminal plasma total antioxidant capacity and vitamin- C levels in asthenozoospermia: a case- control study

    Directory of Open Access Journals (Sweden)

    Ali Bidmeshkipour

    2010-03-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Defective sperm function is now recognized as one of the most important causes of male infertility. Seminal plasma possesses a rich source of different enzymatic and non-enzymatic antioxidants such as vitamin C (ascorbic acid that protect spermatozoa against oxidative stress as one of the mediators of infertility causing sperm dysfunction and low sperm quality. The aim of this study was investigation of seminal total antioxidant capacity and determination of vitamin C effects on sperm motility. "n"nMethods: We designed a case-control study with a total subject of 62 males. Sperm parameters were analyzed according to World Health Organization guidelines (WHO, 1999. Total antioxidant capacity and vitamin C level of seminal plasma were measured in the 32 normozoospermic as the control group and 32 asthenospermic men as the case group using FRAP (Ferric Reducing of Antioxidants Powers and RP-HPLC (Reverse Phase High Performance Liquid Chromatography methods, respectively. "n"nResults: Our results indicated that total antioxidant capacity levels in the seminal plasma of asthenospermic men were significantly lower than healthy men (p=0.002. In addition, we found a positive correlation between reduced total

  2. Spectrophotometric determination of total proteins in blood plasma: a comparative study among dye-binding methods

    Directory of Open Access Journals (Sweden)

    Dimas Augusto Morozin Zaia

    2005-05-01

    Full Text Available A comparative study between the biuret method (standard method for total proteins and spectrophotometric methods using dyes (Bradford, 3',3",5',5"-tetrabromophenolphthalein ethyl ester-TBPEE, and erythrosin-B was carried out for the determination of total proteins in blood plasma from rats. Bradford method showed the highest sensitivity for proteins and biuret method showed the lowest. For all the methods, the absorbance for different proteins (BSA, casein, and egg albumin was measured and Bradford method showed the lowest variation of absorbance. The concentration of total protein obtained by using Bradford method was not statistically different (p>0.05 from concentration of total protein obtained by the biuret method. But in regard to erythrosin-B and TBPEE methods the concentrations of total protein were statistically different (pA determinação de proteínas totais em plasma sangüíneo é importante em diversas áreas de pesquisa. Um estudo comparativo entre o método de biureto (método padrão para proteínas totais e diversos métodos que utilizam corantes (Bradford, tetrabromofenolftaleína etil éster-TBPEE, e eritrosina-B foi realizado para a determinação de proteínas totais em plasma sangüíneo de ratos. O método de Bradford mostrou a maior sensibilidade para proteínas e o de biureto a menor. Para todos os métodos, as absorbâncias para diferentes proteínas (BSA, caseína, e ovoalbumina foram medidas e o método de Bradford mostrou a menor variação da absorbância. Utilizando o método de Bradford a concentração de proteínas totais obtida não foi estatisticamente diferente (p>0.05 daquela obtida pelo método do biureto. Porém, para os métodos da eritrosina-B e TBPEE as concentrações de proteínas totais foram estatisticamente diferentes (p<0.05 da obtida pelo método de biureto. Portanto o método de Bradford pode ser utilizado no lugar do método de biureto para a determinação de proteínas totais em plasma sangüíneo.

  3. Fasting ghrelin levels in physically active women: relationship with menstrual disturbances and metabolic hormones.

    Science.gov (United States)

    De Souza, Mary Jane; Leidy, Heather J; O'Donnell, Emma; Lasley, Bill; Williams, Nancy I

    2004-07-01

    Recent findings support a role for ghrelin in the regulation of energy homeostasis and possibly reproductive function. The primary purpose of this study was to test whether differences in fasting ghrelin levels exist in exercising women with differing menstrual and metabolic status. Menstrual cycle status was defined as sedentary ovulatory (SedOvul; n = 10, cycles = 26), exercising ovulatory (ExOvul; n = 11, cycles = 22), exercising luteal phase defect/anovulatory (ExLPD/Anov; n = 11, cycle = 27), and exercising amenorrheic (ExAmen; n = 8, cycle = 16). Subjects were 27.7 +/- 1.2 yr of age, weighed 60.2 +/- 3.3 kg, and had menstrual cycle lengths of 28.4 +/- 0.9 d. Blood was collected during the follicular phase (d 2-9) of each menstrual cycle and analyzed for total ghrelin, insulin, total T(3), and leptin. Ghrelin was significantly elevated by approximately 85% in the ExAmen category (725.5 +/- 40.8 pmol/liter) when compared with all other categories (P hormonal profile consistent with chronic energy deficiency in exercising women across a range in menstrual status and introduces ghrelin as a potential supplementary indicator that uniquely discriminates amenorrheic athletes from athletes with other menstrual disturbances.

  4. 2型糖尿病患者外源性给予胰升血糖素对肥胖与血浆Ghrelin的影响%Effects of exogenous glucagon on plasma ghrelin and obesity in type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    林少达; 段红艳; 林楚佳; 陈仲贤

    2011-01-01

    目的 探讨肥胖及非肥胖2型糖尿病(T2DM)患者胰岛素抵抗(IR)与生长激素释放肽Gh-relin分泌的关系.方法 肥胖T2DM患者26例(Ob+T2DM组)及非4肥胖T2DM患者32例(Nob+T2DM组),正常对照30名(NC组)行胰升血糖素-GP释放试验,同步取血测定血浆Ghrelin和C-P.结果 (1)Ob+T2DM组空腹Gllrelin水平低于NC组和Nob+T2DM组(P<0.05或P<0.01);Ob+T2DM组FC-P及胰岛素抵抗指数(HOMA2-IR)高于NC组和Nob+T2DM组(P<0.01或P<0.05).静脉推注胰升血糖素后,NC组Ghrelin水平显著下降(P<0.01),肥胖及非肥胖T2DM组Ghrelin水平无显著性改变.(2)Pearson相关分析显示空腹血浆Ghrelin水平分别与WC、BMI、体脂百分比、体脂重量呈负相关;多元回归分析显示腰围(WC)是Ghrelin水平的负性预测因子(回归方程Y=4.814-0.0265X).(3)Ob+T2DM组中,空腹血浆Ghrelin水平分别与WC、BMI、体脂百分比、体脂重量、HOMA2-IR呈负相关.结论 外源性给予胰升血糖素对T2DM患者Ghrelin抑制效应减弱;肥胖T2DM患者血浆Ghre-lin水平较非肥胖患者明显降低,且与WC、BMI、体脂百分比、体脂重量、HOMA2-LR负相关;中心性肥胖T2DM患者血浆Ghrelin水平下降与LR有关.%Objective To study effects of exogenous glucagon on plasma ghrelin and obesity in type 2 diabetic patients.Methods The study subjects included the obese type 2 diabetics (Ob+T2DM, n=26), non-obese type 2 diabetics (NOb+T2DM, n=32) and normal control (NC, n=30).Plasma ghrelin and C-peptide were measured during glucagon stimulation test.Results The percent ghrelin inhibition induced by exogenous glucagon was lower in non-obese and obese T2DM (- 0.1% and -4.1%,respectively with inter-subgroup difference at P<0.05) than in normal control (- 13.2 %)(all P<0.01).The plasma ghrelin was negatively correlated with waist circumference, BMI and body fat mass (r value of -0.301 and P<0.01; r=-0.25 and P<0.05; r=-0.26 and P<0.05, respectively) in normal control

  5. Changes in ghrelin, CCK, GLP-1, and peroxisome proliferator-activated receptors in a hypoxia-induced anorexia rat model.

    Science.gov (United States)

    Duraisamy, Arul Joseph; Bayen, Susovan; Saini, Supriya; Sharma, Alpesh Kumar; Vats, Praveen; Singh, Shashi Bala

    2015-01-01

    A high-altitude environment causes appetite loss in unacclimatised humans, leading to weight reduction. Ghrelin, cholecystokinin (CCK), and glucagon like peptide-1 (GLP-1), are gut hormones involved in the regulation of food intake and energy metabolism. The liver is an important site of metabolic regulation, and together with the gut it plays a role in food intake regulation. This study intends to study the time-dependent changes occurring in plasma gut hormones, PPARα, PPARδ, and PGC1α, in the stomach and liver during hypoxia. Male Sprague Dawley rats were exposed to hypobaric hypoxia in a decompression chamber at 7620 m for different durations up to seven days. Hypoxia increased circulating ghrelin from the third day onwards while CCK and GLP-1 decreased immediately. An increase in ghrelin, ghrelin receptor protein levels, and GOAT mRNA levels in the stomach was observed. Stomach cholecystokinin receptor (CCKAR), PPARα, and PPARδ decreased. Liver CCKAR decreased during the first day of hypoxia and returned to normal levels from the third day onwards. PPARα and PGC1α expression increased while PPARδ protein levels reduced in the liver on third day. Hypoxia alters the expression of ghrelin and ghrelin receptor in the stomach, CCKAR in the liver, and PPAR and its cofactors, which might be possible role players in the contribution of gut and liver to anorexia at high altitude.

  6. Ghrelin is a possible new predictor associated with executive function in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Chen, Siting; Zuo, Xuyang; Li, Yuan; Jiang, Tian; Zhang, Nan; Dai, Fang; Chen, Qiaoer; Zhang, Qiu

    2017-05-01

    The aim of the present research was to study the ghrelin level, executive function and their possible association in patients with type 2 diabetes mellitus. A total of 370 people were recruited between March 2015 and March 2016 in this study. Among them, 212 participants were patients with type 2 diabetes mellitus and 158 participants were included as the control group. Their blood sample was analyzed for the level of ghrelin and other clinical indexes. Cognitive function was measured by the Montreal Cognitive Assessment, and executive function was evaluated by the Wisconsin Card Sorting Test. In the type 2 diabetes mellitus group, age, years of education, duration of diabetes, fasting blood glucose, glycated hemoglobin, hypertension and waist-to-hip ratio were correlated with total Montreal Cognitive Assessment scores. No association was found between ghrelin level and total Montreal Cognitive Assessment score in patients with type 2 diabetes mellitus. However, ghrelin was found to be a significant predictor for executive function impairment measured by the Wisconsin Card Sorting Test in patients with type 2 diabetes mellitus. The level of serum ghrelin might be a biomarker of executive function and become a strong predictor of executive function impairment in patients with type 2 diabetes mellitus. Ghrelin might have a potential protective effect against cognitive function impairment in type 2 diabetes patients. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  7. Progress on Ghrelin in Poultry%禽类 Ghrelin 研究进展

    Institute of Scientific and Technical Information of China (English)

    陈文明; 何敏; 杨欢

    2015-01-01

    The peptide hormone ghrelin is secreted mainly by stomach,and is the only ligand that was found for growth hormone releasing hormone receptor to date.There are two forms of ghrelins exist in the body:N-octanoyl-modified ghrelin and des-acyl ghrelin,and this modification is essential for the activity of ghrelin.Ghrelin is widely distributed in various tissues in the body,with a variety of biological functions:regulating the release of growth hormone,food intaking,energy balance and so on.At present there are many reports related to the rodent animal ghrelin and the corresponding researches have been successful, but the study on poultry ghrelin lags behind,there are many aspects of poultry ghrelin to make clear.This paper made a simple summarize on the research of the poultry ghrelin about the molecular structure,tissue distribution and biological functions,hoping to provide reference for the study of ghrelin in poultry.%Ghrelin主要是由胃分泌的一种肽类激素,是迄今发现的生长激素促分泌素受体的唯一内源性配体。其在体内具有 N-端辛酰基化和 N-端去辛酰基化两种存在形式,N-末端辛酰基化对保证其生物活性是必需的。Ghrelin 广泛分布于机体各种组织中,具有调节生长激素释放、摄食和能量平衡等多种生物学功能。目前关于啮齿类动物 Ghrelin 的相关报道较多,研究已比较透彻,而对于禽类 Ghrelin 的研究则相对滞后,还有许多值得一步研究的地方。论文就近年来关于禽类 Ghrelin 的分子结构、组织分布、生物功能的研究做一概述,以期为禽类 Ghrelin 的研究提供参考。

  8. [Determination of total sulfur in coal by inductively coupled plasma atomic emission spectrometry].

    Science.gov (United States)

    Liu, Dong-yan; Zhang, Yuan-li

    2002-02-01

    A direct method was reported for the determination of total sulfur in coal by inductively coupled plasma atomic emission spectrometry (ICP-AES). The dissolution conditions of coal samples as well as interference conditions of hydrochloric acid and matrix were studied. The recommended method not only proved to be simple and rapid than traditional gravimetric method but show satisfying precision and accuracy as well. The results of samples are as same as gravimetry. The recoveries are more than 96%, and the relative standard deviation of six samples are less than 3%.

  9. Oral vitamin B12 supplementation reduces plasma total homocysteine concentration in women in India.

    Science.gov (United States)

    Yajnik, Chittaranjan S; Lubree, Himangi G; Thuse, Nileema V; Ramdas, Lalita V; Deshpande, Swapna S; Deshpande, Vaishali U; Deshpande, Jyoti A; Uradey, Bhagyashree S; Ganpule, Anjali A; Naik, Sadanand S; Joshi, Niranjan P; Farrant, Hannah; Refsum, Helga

    2007-01-01

    People in India have a high prevalence of low vitamin B12 status and high plasma total homocysteine (tHcy) concentrations. In a proof of principle trial, we studied the effect of oral vitamin B12 (500 microg) and/or 100 g cooked green leafy vegetables (GLV) every alternate day in a 2x2 factorial design over a 6-week period. Forty-two non-pregnant vegetarian women (age 20-50 years) were randomly allocated to four study groups. Clinical measurements were made at the beginning and at the end of the study, and blood samples were collected before, and 2 and 6 weeks after commencement of intervention. Forty women completed the trial. Twenty-six women had low vitamin B12 status (15 micromol/L). GLV supplementation did not alter plasma folate or tHcy. Vitamin B12 supplementation increased plasma vitamin B12 concentration (125 to 215 pmol/L, p homocysteine (tHcy) concentrations.

  10. Seasonal foraging patterns of forest-grazing Japanese Black heifers with increased plasma total antioxidant capacity.

    Science.gov (United States)

    Haga, Satoshi; Nakano, Miwa; Nakao, Seiji; Hirano, Kiyoshi; Yamamoto, Yoshito; Sasaki, Hiroyuki; Ishizaki, Hiroshi

    2016-02-01

    Forest-grazing enables the intake of high total antioxidant capacity (TAC) plants that might be beneficial for the TAC status of cattle. This study evaluated the relation between the seasonal foraging patterns of forest-grazing Japanese Black (JB) heifers or the TAC levels in shrubs and trees and the changes of plasma TAC. We examined 12 JB heifers, four each of which were allocated to forest-grazing (F), pasture-grazing, and pen-housed groups. The plasma TAC level in F heifers on July 26, August 13, 30 and September 17 were significantly higher than those on April 27 and June 4 (P < 0.05). In F group, the mean rates of foraging frequency (FF) of shrubs and trees during July 5-8 and September 13-16 were much higher than that during May 31-June 3 (P < 0.05). The rate of FF of grass significantly decreased later in the season (P < 0.05). The mean TAC levels in these shrubs and trees were higher than those in grasses, concentrates, and timothy hay. Results suggest that an important factor in the increase of plasma TAC in forest-grazing cattle might be the increased foraging of TAC-rich shrubs and trees during summer-fall.

  11. Proghrelin peptides: Desacyl ghrelin is a powerful inhibitor of acylated ghrelin, likely to impair physiological effects of acyl ghrelin but not of obestatin A study of pancreatic polypeptide secretion from mouse islets

    DEFF Research Database (Denmark)

    Kumar, Rajesh; Salehi, Albert; Rehfeld, Jens F;

    2010-01-01

    Proghrelin, produced by the ghrelin (A-like) cells of the gastric mucosa, gives rise to cleavage products, including desacyl ghrelin, acyl ghrelin and obestatin. The products are thought to be secreted concomitantly. In an earlier study we found acyl ghrelin and obestatin, but not desacyl ghrelin...

  12. Serial changes in plasma total cortisol, plasma free cortisol, and tissue cortisol activity in patients with septic shock: an observational study

    National Research Council Canada - National Science Library

    Cohen, Jeremy; Smith, Melissa Lassig; Deans, Renae V; Pretorius, Carel J; Ungerer, Jacobus P J; Tan, Terrence; Jones, Mark; Venkatesh, Bala

    2012-01-01

    Published data on adrenocortical function in septic shock have enrolled patients at various stages of critical illness and predominantly used plasma total cortisol, with minimal information on serial changes...

  13. Plasma free and total carnitine measured in children by tandem mass spectrometry.

    Science.gov (United States)

    Osorio, J H; Pourfarzam, M

    2002-11-01

    Free and total carnitine quantification is important as a complementary test for the diagnosis of unusual metabolic diseases, including fatty acid degradation disorders. The present study reports a new method for the quantification of free and total carnitine in dried plasma specimens by isotope dilution electrospray tandem mass spectrometry with sample derivatization. Carnitine is determined by looking for the precursor of ions of m/z = 103 of N-butylester derivative, and the method is validated by comparison with radioenzymatic assay. We obtained an inter- and intra-day assay coefficient of variation of 4.3 and 2.3, respectively. Free and total carnitine was analyzed in 309 dried plasma spot samples from children ranging in age from newborn to 14 years using the new method, which was found to be suitable for calculating reference age-related values for free and total carnitine (less than one month: 19.3 +/- 2.4 and 23.5 +/- 2.9; one to twelve months: 28.8 +/- 10.2 and 35.9 +/- 11.4; one to seven years: 30.7 +/- 10.3 and 38.1 +/- 11.9; seven to 14 years: 33.7 +/- 11.6, and 43.1 +/- 13.8 micro M, respectively). No difference was found between males and females. A significant difference was observed between neonates and the other age groups. We compare our data with reference values in the literature, most of them obtained by radioenzymatic assay. However, this method is laborious and time consuming. The electrospray tandem mass spectrometry method presented here is a reliable, rapid and automated procedure for carnitine quantitation.

  14. Plasma free and total carnitine measured in children by tandem mass spectrometry

    Directory of Open Access Journals (Sweden)

    J.H. Osorio

    2002-11-01

    Full Text Available Free and total carnitine quantification is important as a complementary test for the diagnosis of unusual metabolic diseases, including fatty acid degradation disorders. The present study reports a new method for the quantification of free and total carnitine in dried plasma specimens by isotope dilution electrospray tandem mass spectrometry with sample derivatization. Carnitine is determined by looking for the precursor of ions of m/z = 103 of N-butylester derivative, and the method is validated by comparison with radioenzymatic assay. We obtained an inter- and intra-day assay coefficient of variation of 4.3 and 2.3, respectively. Free and total carnitine was analyzed in 309 dried plasma spot samples from children ranging in age from newborn to 14 years using the new method, which was found to be suitable for calculating reference age-related values for free and total carnitine (less than one month: 19.3 ± 2.4 and 23.5 ± 2.9; one to twelve months: 28.8 ± 10.2 and 35.9 ± 11.4; one to seven years: 30.7 ± 10.3 and 38.1 ± 11.9; seven to 14 years: 33.7 ± 11.6, and 43.1 ± 13.8 µM, respectively. No difference was found between males and females. A significant difference was observed between neonates and the other age groups. We compare our data with reference values in the literature, most of them obtained by radioenzymatic assay. However, this method is laborious and time consuming. The electrospray tandem mass spectrometry method presented here is a reliable, rapid and automated procedure for carnitine quantitation.

  15. Total Extracellular Small RNA Profiles from Plasma, Saliva, and Urine of Healthy Subjects

    Science.gov (United States)

    Yeri, Ashish; Courtright, Amanda; Reiman, Rebecca; Carlson, Elizabeth; Beecroft, Taylor; Janss, Alex; Siniard, Ashley; Richholt, Ryan; Balak, Chris; Rozowsky, Joel; Kitchen, Robert; Hutchins, Elizabeth; Winarta, Joseph; McCoy, Roger; Anastasi, Matthew; Kim, Seungchan; Huentelman, Matthew; Van Keuren-Jensen, Kendall

    2017-01-01

    Interest in circulating RNAs for monitoring and diagnosing human health has grown significantly. There are few datasets describing baseline expression levels for total cell-free circulating RNA from healthy control subjects. In this study, total extracellular RNA (exRNA) was isolated and sequenced from 183 plasma samples, 204 urine samples and 46 saliva samples from 55 male college athletes ages 18–25 years. Many participants provided more than one sample, allowing us to investigate variability in an individual’s exRNA expression levels over time. Here we provide a systematic analysis of small exRNAs present in each biofluid, as well as an analysis of exogenous RNAs. The small RNA profile of each biofluid is distinct. We find that a large number of RNA fragments in plasma (63%) and urine (54%) have sequences that are assigned to YRNA and tRNA fragments respectively. Surprisingly, while many miRNAs can be detected, there are few miRNAs that are consistently detected in all samples from a single biofluid, and profiles of miRNA are different for each biofluid. Not unexpectedly, saliva samples have high levels of exogenous sequence that can be traced to bacteria. These data significantly contribute to the current number of sequenced exRNA samples from normal healthy individuals. PMID:28303895

  16. 2型糖尿病患者应用二甲双胍治疗前后血浆胃促生长素及YY肽水平%Plasma ghrelin and peptide YY levels in patients with type 2 diabetes before and after metformin treatment

    Institute of Scientific and Technical Information of China (English)

    吴朝明; 王靓; 金建; 钱掩映

    2011-01-01

    目的 观察二甲双胍治疗对新诊断2型糖尿病患者血浆胃促生长素、YY肽(PYY)水平的影响,探讨二甲双胍对2型糖尿病患者体重影响个体差异性的机制.方法 采用前瞻性巢式病例对照研究作为研究设计方案.64例新诊断2型糖尿病患者应用二甲双胍治疗12周,根据治疗后体重的变化情况,分为体重减轻组及体重未减轻组,治疗前后测定空腹血浆胃促生长素、PYY水平及相关代谢指标.结果 2型糖尿病患者经二甲双胍治疗后空腹血浆胃促生长素水平均较治疗前明显下降[(10.71 +2.68对11.81±3.19)ng/ml,P<0.05],空腹血浆PYY水平均较治疗前明显升高[(136.86±39.14对128.42±37.31)pg/ml,P<0.05].治疗后有43.7%的2型糖尿病患者出现体重明显下降.体重减轻组在治疗后空腹血浆胃促生长素水平下降16.6%,降幅高于体重未减轻组的6.2%(P<0.05);体重减轻组在治疗后空腹血浆PYY水平升高10.8%,升幅高于体重未减轻组的3.5%(P<0.05).结论 2型糖尿病患者二甲双胍治疗后体重明显减轻者较体重基本保持不变者,空腹血浆胃促生长素水平降低更显著,空腹血浆PYY水平升高更显著,具体机制还有待进一步研究.%Objective To investigate the effects of metformin on plasma ghrelin and peptide YY (PYY)levels in newly-diagnosed type 2 diabetic patients,and to study the impact of metformin on body weight.Methods A prospective nested case-control study was designed as a research protocol.Sixty four newly-diagnosed type 2 diabetic patients were treated with metformin for 12 weeks.The patients were divided into two groups:weight loss group and non-weight loss group according to the changes in body weight after metformin treatment.Fasting plasma ghrelin and PYY levels and other metabolic parameters were measured before and after metformin treatment.Results Fasting plasma ghrelin level was significantly decreased in the patients after metformin

  17. Hypothalamic mTOR signaling mediates the orexigenic action of ghrelin.

    Directory of Open Access Journals (Sweden)

    Luís Martins

    Full Text Available Current evidence suggests that ghrelin, a stomach derived peptide, exerts its orexigenic action through specific modulation of Sirtuin1 (SIRT1/p53 and AMP-activated protein kinase (AMPK pathways, which ultimately increase the expression of agouti-related protein (AgRP and neuropeptide Y (NPY in the arcuate nucleus of the hypothalamus (ARC. However, there is a paucity of data about the possible action of ghrelin on alternative metabolic pathways at this level. Here, we demonstrate that ghrelin elicits a marked upregulation of the hypothalamic mammalian target of rapamycin (mTOR signaling pathway. Of note, central inhibition of mTOR signaling with rapamycin decreased ghrelin's orexigenic action and normalized the mRNA expression of AgRP and NPY, as well as their key downstream transcription factors, namely cAMP response-element binding protein (pCREB and forkhead box O1 (FoxO1, total and phosphorylated. Taken together, these data indicate that, in addition to previous reported mechanisms, ghrelin also promotes feeding through modulation of hypothalamic mTOR pathway.

  18. Characteristic features of ghrelin cells in the gastrointestinal tract and the regulation of stomach ghrelin expression and production

    Institute of Scientific and Technical Information of China (English)

    Zheng Zhao; Takafumi Sakai

    2008-01-01

    Ghrelin was isolated as an endogenous ligand for the GH secretagogue receptor from the rat stomach. Although physiological effects of ghrelin have been revealed by numerous studies, the regulation of stomach ghrelin remains obscure, and the factor that directly regulates ghrelin expression and production has not been identified. Here, we show some data regarding the characteristic features of ghrelin cells and the regulation of stomach ghrelin. In the gastrointestinal tract, ghrelin cells were identified as opened- and closed-type cells, and it was found that the number of ghrelin cells decreased from the stomach to the colon. The postnatal change in number of ghrelin cells in the stomach showed a sexually dimorphic pattern, indicating a role of estrogen in the regulation of stomach ghrelin. In vitro studies revealed that estrogen stimulated both ghrelin expression and production and that treatment with formestane, an aromatase (estrogen synthetase) inhibitor, decreased ghrelin expression level. On the other hand, leptin was found to inhibit both basal and estrogen-stimulated ghrelin expression. Moreover, both aromatase mRNA-expressing cells and leptin cells were found to be located close to ghrelin cells in the gastric mucosa. Furthermore, we found an inverse relationship between gastric ghrelin and leptin levels in a fasting state, and we revealed relative changes in expression of gastric ghrelin, estrogen and leptin in the postnatal rats. We propose that gastric estrogen and leptin directly regulate stomach ghrelin and that the balance control through gastric estrogen and leptin contributes to the altered ghrelin expression level in some physiological states.

  19. Ghrelin signalling and obesity: at the interface of stress, mood and food reward.

    Science.gov (United States)

    Schellekens, Harriët; Finger, Beate C; Dinan, Timothy G; Cryan, John F

    2012-09-01

    The neuronal circuitry underlying the complex relationship between stress, mood and food intake are slowly being unravelled and several studies suggest a key role herein for the peripherally derived hormone, ghrelin. Evidence is accumulating linking obesity as an environmental risk factor to psychiatric disorders such as stress, anxiety and depression. Ghrelin is the only known orexigenic hormone from the periphery to stimulate food intake. Plasma ghrelin levels are enhanced under conditions of physiological stress and ghrelin has recently been suggested to play an important role in stress-induced food reward behaviour. In addition, chronic stress or atypical depression has often demonstrated to correlate with an increase in ingestion of caloric dense 'comfort foods' and have been implicated as one of the major contributor to the increased prevalence of obesity. Recent evidence suggests ghrelin as a critical factor at the interface of homeostatic control of appetite and reward circuitries, modulating the hedonic aspects of food intake. Therefore, the reward-related feeding of ghrelin may reveal itself as an important factor in the development of addiction to certain foods, similar to its involvement in the dependence to drugs of abuse, including alcohol. This review will highlight the accumulating evidence demonstrating the close interaction between food, mood and stress and the development of obesity. We consider the ghrelinergic system as an effective target for the development of successful anti-obesity pharmacotherapies, which not only affects appetite but also selectively modulates the rewarding properties of food and impact on psychological well-being in conditions of stress, anxiety and depression. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Impact of bread making on fructan chain integrity and effect of fructan enriched breads on breath hydrogen, satiety, energy intake, PYY and ghrelin.

    Science.gov (United States)

    Morris, C; Lynn, A; Neveux, C; Hall, A C; Morris, G A

    2015-08-01

    Recently, there has been considerable interest in the satiety inducing properties of inulin type fructans (ITF) as a tool for weight management. As a staple food, breads provide an excellent vehicle for ITF supplementation however the integrity of the ITF chains and properties upon bread making need to be assessed. Breads enriched with 12% fructooligosaccharides (FOS) and 12% inulin were baked and the degree of polymerisation of fructans extracted from the breads were compared to those of pure compounds. An acute feeding study with a single blind cross-over design was conducted with 11 participants to investigate the effect of ITF enriched breads on breath hydrogen, self-reported satiety levels, active ghrelin, total PYY and energy intake. Size exclusion chromatography indicated that little or no depolymerisation of inulin occurred during bread making, however, there was evidence of modest FOS depolymerisation. Additionally, ITF enriched breads resulted in increased concentrations of exhaled hydrogen although statistical significance was reached only for the inulin enriched bread (p = 0.001). There were no significant differences between bread types in reported satiety (p = 0.129), plasma active ghrelin (p = 0.684), plasma PYY (p = 0.793) and energy intake (p = 0.240). These preliminary results indicate that inulin enriched bread may be a suitable staple food to increase ITF intake. Longer intervention trials are required to assess the impact of inulin enriched breads on energy intake and body weight.

  1. Betaine as a determinant of postmethionine load total plasma homocysteine before and after B-vitamin supplementation.

    NARCIS (Netherlands)

    Holm, P.I.; Bleie, O.; Ueland, P.M.; Lien, E.A.; Refsum, H.; Nordrehaug, J.E.; Nygard, O.

    2004-01-01

    OBJECTIVE: Betaine is a substrate in the betaine-homocysteine methyltransferase reaction, converting homocysteine to methionine. There are only sparse data on plasma betaine as a determinant of the plasma total homocysteine (tHcy) concentration. METHODS AND RESULTS: Ninety patients undergoing corona

  2. Effects of amino acids infused into the vein on ghrelin-induced GH, insulin and glucagon secretion in lactating cows.

    Science.gov (United States)

    Fukumori, Rika; Yokotani, Akinori; Sugino, Toshihisa; Itoh, Fumiaki; Kushibiki, Shiro; Shingu, Hiroyuki; Moriya, Naoko; Hasegawa, Yoshihisa; Kojima, Masayasu; Kangawa, Kenji; Obitsu, Taketo; Taniguchi, Kohzo

    2011-04-01

    To investigate the effects of amino acids on ghrelin-induced growth hormone (GH), insulin and glucagon secretion in lactating dairy cattle, six Holstein cows were randomly assigned to two infusion treatments in a cross-over design. Mixture solution of amino acids (AMI) or saline (CON) was continuously infused into the left side jugular vein via catheter for 4 h. At 2 h after the start of infusion, synthetic bovine ghrelin was single injected into the right side jugular vein through the catheter. Ghrelin injection immediately increased plasma GH, glucose and non-esterified fatty acids (Pghrelin injection in both treatments. The peak value of plasma insulin concentration was greater in AMI compared with CON (Pghrelin action which in turn enhances insulin and glucagon secretions in lactating cows.

  3. 游泳运动对高脂诱导肥胖SD大鼠Ghrelin表达的影响%Effects of swimming exercise on Ghrelin levels in high-diet induced obesity SD rats

    Institute of Scientific and Technical Information of China (English)

    高雅; 潘天荣; 王长江

    2013-01-01

    目的:观察游泳运动干预后肥胖大鼠血清及下丘脑Ghrelin水平的变化,探讨其在肥胖及代谢紊乱中的作用.方法:SD大鼠50只随机分为普食(NC,n=10)组和高脂(HD,n=40)组.筛选出成功建立肥胖模型20只随机分为肥胖对照(OB)组、游泳(SWI)组,各10只.SWI组予以每天1 h,每周5 d,共行6周游泳训练;OB组及NC组予等剂量蒸馏水灌胃.分别测定干预6周前后各组体重(BW)、空腹血糖(FPG)、三酰甘油(TG)、总胆固醇(TCH)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)及血清Ghrelin.免疫组织化学法检测各组大鼠下丘脑Ghrelin表达水平.结果:干预前,OB组、SWI组均较NC组BW、FPG、TG、TCH、FINS、HOMA-IR显著升高,Ghrelin明显降低(P<0.01);干预后,SWI组均较OB组BW、TG、TCH、FPG、FINS、HOMA-IR明显降低,Ghrelin水平升高(P<0.01).免疫组织化学显示OB组下丘脑Ghrelin表达较NC组降低(P<0.01),SWI组较OB组升高(P<0.05).结论:游泳运动可改善胰岛素敏感性并减轻体重,降低肥胖大鼠Ghrelin水平.%Objective: To observe the changes of Ghrelin level in serum and hypothalamus of high-diet induced obesity rats after 6-week swimming exercise,and to investigate the association of Ghrelin with obesity and metabolic syndrome. Methods:Fifty SD rats were randomly divided into normal diet group( NC,n = 10) and high fat diet group(HD,n =40). Obesity models(n =20) were established from the HD group, and equally assigned to obesity group ( OB) and swimming exercise group ( SWI) . The SWI group received standard swimming exercise 1 hour/day,5 day/week for 6 weeks,and the other two groups were given distilled water. Their body weight( BW) , fasting plasma glucose(FPG) ,triglyceride(TG) ,total cholesterol(TCH) ,fasting insulin(FINS) ,H0MA index and fasting Ghrelin were measured 6 weeks before and after the intervene; the Ghrelin expression in the hypothalamus was detected by immunohistochemistry. Results:The BW

  4. 二甲双胍和吡格列酮对初诊糖代谢异常伴腹型肥胖患者血清ghrelin水平的影响%Effects of metformin and pioglitazone on plasma ghrelin in patients with newly diagnosed abnormal glucose metabolism and abdominal obesity

    Institute of Scientific and Technical Information of China (English)

    张淼; 郭毅飞; 时立新; 吴丹荣; 张松; 胡颖; 徐毅; 林巧

    2012-01-01

    Objective To investigate the effects of metformin and pioglitazone on plasma ghrelin in patients with newly diagnosed abnormal glucose metabolism and abdominal obesity.Methods From April to September 2010,39 patients with abnormal glucose metabolism (including impaired glucose tolerance and newly diagnosed type diabetes mellitus,glycated hemoglobin A1c(HbA1c) <7% ) and obesity were enrolled in the study.They were randomly assigned to metformin group(500 mg tid,n =20,15 females and 5 males,aged (51±9) years,MET group) or pioglitazone group (30 mg/d,n =19,11 females and 8 males,aged (53 ±7) years,PIO group) on the basis of diet and exercise therapy for3 months.Three males in PIO group with drawed because of itching and edema.At baseline and after 3 months,plasma glucose,serum insulin and ghrelin levels during oral glucose tolerance test( OGTT,0 min,0.5,1.0,2.0,3.0 h),body weight,body mass index(BMI),HbA1c,etc were measured.The t test or Wilcoxon rank-sum test was used for statistical analysis. Partial correlation and multiple regression analysis were performed to examine the association between serum ghrelin levels and influencing factors.Results ( 1 ) In PIO group,serum ghrelin levels after treatment were OGTT 0 min (1069 ±467)ng/L,0.5 h (898 ±407)ng/L,1.0 h (812 ±371) ng/L,2.0 h (705 ± 328) ng/L and 3.0 h ( 1059 ± 606 ) ng/L,respectively.All increased than those before treatment ( (905 ±449),(688 ±378),(614 ±358),(572 ± 334)and(720 ±403)ng/L,Z value was from -2.354 to - 3.351,respectively,all P < 0.05 ).(2) In MET group,serum ghrelin levels at OGTT 0 min,1.0,2.0,3.0 h after treatment were (731 ± 241 ),(642 ± 208 ),( 525 ± 195 ),(462 ± 146 ) and ( 611 ± 267 ) ng/L,respectively.Compared with the ghrelin levels before treatment( (731 ± 241 ),(642 ± 208 ),(525 ± 195 ),(462 ± 146) and (611 ± 267)ng/L),only the difference at 0 min,2.0,3.0 h was statistically significant (all P<0.05).Serum ghrelin levels of MET group at OGTT 0.5,1.0 and 3.0 h

  5. Diet-Induced Obesity and Ghrelin Effects on Pituitary Gonadotrophs: Immunohistomorphometric Study in Male Rats

    Directory of Open Access Journals (Sweden)

    Ristic Natasa

    2016-02-01

    Full Text Available Objective: The close relationship between energy metabolism, nutritional state, and reproductive physiology suggests that nutritional and metabolic disorders can disrupt normal reproductive function and fertility. Considering the importance of leptin and ghrelin effects in regulation of the hypothalamic-pituitary-gonadal axis, the objective of this study was to investigate the influence of obesity and centrally applied ghrelin on immunohistochemical appearance and quantitative morphology of the pituitary follicle-stimulating hormone (FSH and luteinizing hormone (LH producing cells in adult male rats. Materials and Methods: In this experimental study, animals were given two different diets: normal-fat (NF and high-fat (HF, for 4 weeks, corresponding to normal and positive energy balance (n=2×14, respectively. Each group was subsequently divided into two subgroups (n=7 receiving intracerebroventricular (ICV injections of either ghrelin [G, 1 μg/5 μL phosphate buffered saline (PBS] or vehicle (5 μL PBS, control group every 24 hours for five consecutive days. Results: Morphometric analyses showed that in HF control group, the percentage of FSH cells per unit volume of total pituitary gland tissue (in μm3, i.e. volume density (Vvc, was increased (P<0.05 by 9.1% in comparison with the NF controls. After ICV treatment with ghrelin, volume (Vc and volume density (Vvc of FSH cells in ghrelin+NF (GNF and ghrelin+HF (GHF groups remained unchanged in comparison with NF and HF controls. Volume of LH cells in HF control group was increased by 17% (P<0.05, but their Vvc was decreased by 8.3% (P<0.05 in comparison with NF controls. In GNF group, the volume of LH cells increased by 7% (P<0.05, in comparison with the NF controls, but in GHF group, the same parameter remained unchanged when compared with HF controls. The central application of ghrelin decreased the Vvc of LH cells only in GNF group by 38.9% (P<0.05 in comparison with the NF control animals

  6. Plasmas pour valorisation totale ou partielle des gaz contenant de l'H2S Plasmas for Total Or Partial Upgrading of H2s Containing Gases

    Directory of Open Access Journals (Sweden)

    Czernichowski A.

    2006-12-01

    Full Text Available Des procédés par plasmas alternatifs au procédé Claus sont proposés pour produire de l'hydrogène et récupérer du soufre à partir des gaz contenant une forte teneur en H2S. Quand la teneur en H2S est moins importante, des techniques plasma peuvent également être utiles pour assister certains étages du procédé classique Claus ou réaliser ce procédé pour des gaz non conventionnels. Les tests allant jusqu'à l'échelle industrielle sont menés dans divers réacteurs à plasmas et les résultats encourageants rapportés de la littérature et de la recherche propre laissent envisager des prochaines applications. Plasma assisted processes are proposed to act as an alternative to the Claus process in order to recover hydrogen and sulphur from high H2S gases. For less concentrated gases plasma techniques may also be inserted into classical Claus plant or may allow treatment of non conventional gases. Up to industrial scale tests are performed using different plasma reactors. The literature-based results as well as our own ones make the future applications quite optimistic.

  7. Effects of nasal continuous positive airway pressure treatment on insulin resistance and ghrelin levels in non-diabetic apnoeic patients with coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    YANG Dan; LIU Zhi-hong; ZHAO Qing; LUO Qin

    2013-01-01

    Background Obesity is a common risk factor for several diseases.Obesity related hormone and increased insulin resistance (IR) may contribute to the effects of obstructive sleep apnoea on cardiovascular consequences.We investigated ghrelin and IR in non-diabetic apnoeic patients with stable coronary heart disease and assessed the effects of continuous positive airway pressure (CPAP).Methods Plasma ghrelin,glucose and insulin were measured in 22 patients with CPAP and 22 matched controls without CPAP at baseline and three months.Indexes including homeostasis model assessment IR (HOMA IR),HOMA S and HOMA β were calculated for the assessment of IR,insulin sensitivity and pancreatic β cell function.Results At three months follow-up,plasma ghrelin levels and HOMA IR in CPAP group were significantly decreased (,P=0.002 and 0.046,respectively) while those in control group increased significantly (P=0.012 and 0.009,respectively).Significant moderate correlations were found between ghrelin vs.HOMA IR and ghrelin vs.HOMA S after CPAP,however,for those without CPAP,no significant associations were observed.Conclusions Short-term effective continuous positive airway pressure had a significant effect on lowering plasma ghrelin levels and IR,but not body fat.Further large scale and longer term studies are warranted to corroborate these findings.

  8. Central and peripheral mechanisms by which ghrelin regulates gut motility.

    Science.gov (United States)

    Peeters, T L

    2003-12-01

    Ghrelin is the recently discovered endogenous ligand for the growth hormone secretagogue receptor. This receptor had previously been characterized based on the stimulatory effect of synthetic peptides, enkephalin analogues, on growth hormone secretion by pituitary somatotrophs. Surprisingly, ghrelin is most abundant in the stomach, suggesting that it may have effects beyond the stimulation of growth hormone in the pituitary and that it is a new brain-gut peptide. There is now increasing evidence that ghrelin stimulates motor activity in the gastrointestinal tract. Thus ghrelin induces the migrating motor complex and accelerates gastric emptying. These are effects typical for motilin, the only peptide structurally related to ghrelin. Moreover, the receptors of both peptides are structurally related as well. The motor effects of ghrelin require rather high concentrations, while motilin at high concentrations stimulates growth hormone release. These data suggest cross-reactivity. However, in vitro binding and contractility studies in the rabbit, the classical model to study motilin agonists, show that ghrelin has very weak if any interaction with the motilin receptor. Similarly, in cell lines expressing the receptors for both peptides there is no evidence for cross-reactivity. This corresponds to the fact that the pharmacophore of both peptides is quite different. Therefore, the motor effects must be due to the stimulation of specific central or peripheral ghrelin receptors. In the guinea pig there is evidence from electrophysiology, immunohistochemistry and calcium imaging studies for ghrelin receptors on myenteric neurons. This provides the morphological basis for peripheral effects of ghrelin. In rats, ghrelin, but not motilin, enhances the response of muscle strips to electrical field stimulation by activating cholinergic pathways. In rabbits the opposite is true but some synthetic ghrelin agonists have weak effects which cannot be blocked by motilin antagonists

  9. The Effect of Agave tequilana Weber Inulin on Postprandial Ghrelin Concentration in Obese Patients.

    Science.gov (United States)

    Contreras-Haro, Betsabe; Robles-Cervantes, Jose A; Gonzalez-Ortiz, Manuel; Martinez-Abundis, Esperanza; Espinel-Bermudez, Claudia; Gallegos-Arreola, Martha P; Morgado-Castillo, Karina C

    2017-02-01

    This study was performed to investigate the effect of Agave tequilana Weber inulin on postprandial ghrelin levels in obese patients. A randomized, double-blind, cross-over design was performed. A total of 14 patients were allocated into two groups: one group received a drink that contained 500 mL lemon water, 24 g of A. tequilana Weber inulin, and 75 g glucose and the other group received a placebo drink with 500 mL lemon drink and 75 g of glucose. After a 7-day washout period, the groups were crossed. The primary outcome measure was postprandial ghrelin levels between minute 240 and minute 270. A. tequilana Weber inulin did not change postprandial ghrelin concentration in obese patients.

  10. Different effects of ghrelin, des-acyl ghrelin and obestatin on gastroduodenal motility in conscious rats

    Institute of Scientific and Technical Information of China (English)

    Mineko Fujimiya; Aldhiro Asakawa; Koji Ataka; Ikuo Kato; Akio Inui

    2008-01-01

    Three peptides, ghrelin, des-acyl ghrelin and obestatin are derived from a common prohormone, preproghre-lin by posttranslational processing, originating from endocrine cells in the stomach. To examine the effects of these peptides, we applied the manometric mea-surement of gastrointestinal motility in freely moving conscious rat models. Ghrelin exerts stimulatory ef-fects on the motility of antrum and duodenum in both fed and fasted state of animals. Des-acyl ghrelin exerts inhibitory effects on the motility of antrum, but not on the motility of duodenum in the fasted state of ani-mals. Obestatin exerts inhibitory effects on the motility of antrum and duodenum in the fed state, but not in the fasted state of animals. NPY Y2 or Y4 receptors in the brain may mediate the action of ghrelin, CRF type 2 receptors in the brain mediate the action of des-acyl ghrelin, whereas CRF type 1 and type 2 receptors in the brain mediate the action of obestatin. Vagal affer-ent pathways might be involved in the action of ghre-lin, but not involved in the action of des-acyl ghrelin, whereas vagal afferent pathways might be partially involved in the action of obestatin.

  11. Metabolic aspects of the ghrelin system: Role of acylated and unacylated ghrelin in glucose homeostasis

    NARCIS (Netherlands)

    C. Gauna (Carlotta)

    2007-01-01

    textabstractIn the last decade the discovery of ghrelin, a gut peptide discovered in 1999 by Kojima and colleagues (1), has led to the identification of a complex system that introduced new perspectives in neuroendocrine and metabolic research. Ghrelin is a peptide-hormone of 28 amino acids, predomi

  12. Ghrelin, Des-Acyl Ghrelin, and Obestatin: Regulatory Roles on the Gastrointestinal Motility

    Directory of Open Access Journals (Sweden)

    Mineko Fujimiya

    2010-01-01

    Full Text Available Ghrelin, des-acyl ghrelin, and obestatin are derived from a common prohormone, preproghrelin by posttranslational processing, originating from endocrine cells in the stomach. To examine the regulatory roles of these peptides, we applied the manometric measurement of gastrointestinal motility in freely moving conscious rat or mouse model. Ghrelin exerts stimulatory effects on the motility of antrum and duodenum in both fed and fasted state of animals. Des-acyl ghrelin exerts inhibitory effects on the motility of antrum but not on the motility of duodenum in the fasted state of animals. Obestatin exerts inhibitory effects on the motility of antrum and duodenum in the fed state but not in the fasted state of animals. NPY Y2 and Y4 receptors in the brain may mediate the action of ghrelin, CRF type 2 receptor in the brain may mediate the action of des-acyl ghrelin, whereas CRF type 1 and type 2 receptors in the brain may mediate the action of obestatin. Vagal afferent pathways might be involved in the action of ghrelin, but not involved in the action of des-acyl ghrelin, whereas vagal afferent pathways might be partially involved in the action of obestatin.

  13. The influence of physical activity on ghrelin and IGF-1/IGFBP-3 levels in children and adolescents with type 1 diabetes mellitus.

    Science.gov (United States)

    Huber, Julia; Fröhlich-Reiterer, Elke Elisabeth; Sudi, Karl; Suppan, Elisabeth; Weinhandl, Gudrun; Jasser-Nitsche, Hildegard; Aigner, Reingard; Borkenstein, Martin Helmuth

    2010-09-01

    The aim of the study was to determine the influence of regular physical activity on ghrelin and IGF-1/IGFBP-3 levels during a diabetes camp. Twenty-eight children and adolescents (14 boys; mean age 12.1 yr) with type 1 diabetes mellitus (T1DM, mean duration of diabetes 4.8 yr) attending a 2-wk diabetes camp that features increased regular physical activities have been studied. Serum levels of ghrelin (total and acylated), growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor-bindng protein-3 (IGFBP-3) and insulin were measured in fasting state on day 1 and day 14. Improvement of metabolic control was documented by haemoglobin A1c (HbA1c). Glucose levels and insulin doses were determined daily. Mean insulin dosage decreased from 0.87 to 0.78 U/kg/d, mean HbA1c levels decreased from 8.6 to 8.3%, but the changes were not statistical. There was a significant decline in total ghrelin. IGFBP-3 and IGF-1 decreased also significantly. Total basal ghrelin was inversely related to the change in IGFBP-3. We hypothesize an association between ghrelin and metabolic control in T1DM. Higher ghrelin levels might be associated with poor metabolic control. The dynamic of IGFBP-3 levels appears to be under the influence of basal ghrelin concentrations in T1DM.

  14. Influence of digestive tract reconstruction techniques on plasma ghrelin level and body mass index after subtotal gastectomy%胃次全切除术后不同消化道重建方式对胃癌患者血浆ghrelin水平的影响

    Institute of Scientific and Technical Information of China (English)

    王海涛; 许军; 王荣朝; 张云; 卢麒丞

    2011-01-01

    目的 探讨胃次全切除术后不同的消化道重建方式对血浆ghrelin水平的影响,以及ghrelin与BMI之间的关系.方法 收集81例行根治性手术的T1~3N0M0远端胃癌患者,根据消化道重建方式的不同分为毕Ⅰ式组(30例)、毕Ⅱ式组(25例)和Roux-en-Y组(26例).分别在术前、术后1 d、1周、半年及1年测定血浆ghrelin水平及BMI.结果 术后1 d,毕Ⅰ式、毕Ⅱ式和Roux-en-Y 3组患者ghrelin水平分别为术前水平的(34.2±5.2)%、(37.7±4.7)%和(36.5±4.9)%;术后1周分别为(52.6±6.5)%、(48.3±5.7)%和(48.1±6.0)%,3组比较差异均无统计学意义(均P>0.05).术后半年,3组患者ghrelin水平分别为术前水平的(91.7±7.5)%、(80.4±8.1)%和(75.3±8.3)%;术后1年分别为(95.3±5.1)%、(84.5±6.3)%和(79.9±6.7)%;毕Ⅰ式组ghrelin水平显著高于其他两组(均P<0.01),毕Ⅱ式组高于Roux-en-Y组均(P<0.05).术后1年3组患者BMI分别下降了(2.1±1.1)%、(4.5±1.9)%和(5.7±1.8)%,差异有统计学意义(P<0.05);3组患者ghrelin下降幅度与BMI下降幅度均存在线性相关(均P<0.01).结论 符合解剖生理的毕Ⅰ式消化道重建更加有利于术后血浆ghrelin水平的代偿性恢复;胃次全切除术后血浆ghrelin水平的下降是导致患者体质量减轻的重要原因.%Objective To study the impact of digestive tract reconstruction techniques on plasma ghrelin level and body mass index (BMI) after subtotal gastectomy.Methods Eighty-one patients undergoing subtotal gastrectomy for T1-3N0M0 gastric cancer were divided into three groups according to digestive tract reconstruction techniques, which included Billroth I group (n=30), Billroth II group(n=25) and Roux-en-Y group(n=26). Plasma ghrelin level was determined by radioimmunoassay preoperatively and one day, one week, half a year, and one year after gastrectomy. BMI was similarly recorded.Results Plasma ghrelin levels of three groups decreased sharply to nadir one day after operation, which were

  15. Acute administration of unacylated ghrelin has no effect on Basal or stimulated insulin secretion in healthy humans.

    Science.gov (United States)

    Tong, Jenny; Davis, Harold W; Summer, Suzanne; Benoit, Stephen C; Haque, Ahrar; Bidlingmaier, Martin; Tschöp, Matthias H; D'Alessio, David

    2014-07-01

    Unacylated ghrelin (UAG) is the predominant ghrelin isoform in the circulation. Despite its inability to activate the classical ghrelin receptor, preclinical studies suggest that UAG may promote β-cell function. We hypothesized that UAG would oppose the effects of acylated ghrelin (AG) on insulin secretion and glucose tolerance. AG (1 µg/kg/h), UAG (4 µg/kg/h), combined AG+UAG, or saline were infused to 17 healthy subjects (9 men and 8 women) on four occasions in randomized order. Ghrelin was infused for 30 min to achieve steady-state levels and continued through a 3-h intravenous glucose tolerance test. The acute insulin response to glucose (AIRg), insulin sensitivity index (SI), disposition index (DI), and intravenous glucose tolerance (kg) were compared for each subject during the four infusions. AG infusion raised fasting glucose levels but had no effect on fasting plasma insulin. Compared with the saline control, AG and AG+UAG both decreased AIRg, but UAG alone had no effect. SI did not differ among the treatments. AG, but not UAG, reduced DI and kg and increased plasma growth hormone. UAG did not alter growth hormone, cortisol, glucagon, or free fatty acid levels. UAG selectively decreased glucose and fructose consumption compared with the other treatments. In contrast to previous reports, acute administration of UAG does not have independent effects on glucose tolerance or β-cell function and neither augments nor antagonizes the effects of AG.

  16. Ghrelin response to hedonic eating in underweight and short-term weight restored patients with anorexia nervosa.

    Science.gov (United States)

    Maria Monteleone, Alessio; Monteleone, Palmiero; Dalle Grave, Riccardo; Nigro, Massimiliano; El Ghoch, Marwan; Calugi, Simona; Cimino, Monica; Maj, Mario

    2016-01-30

    Recently, anorexia nervosa (AN) has been conceptualized as a reward-related disorder, and alterations in brain reward processes have been documented in both acute and recovered AN patients. However, the role of endogenous biochemical mediators, such as ghrelin, in the modulation of reward processes has been poorly investigated in this eating disorder. Hedonic eating, that is the consumption of food exclusively for pleasure and not to maintain energy homeostasis, is a useful paradigm to investigate the physiology of food-related reward. Therefore, we assessed the response of peripheral ghrelin to hedonic eating in 7 underweight and 7 recently weight-restored AN patients and compared it to that of previously studied healthy controls. We found that in satiated underweight patients with AN plasma ghrelin levels progressively decreased after the exposure and the consumption of both the favorite and unfavorite food whereas in satiated weight-restored AN patients and satiated healthy controls plasma ghrelin concentrations significantly increased after the exposure to the favorite food and after eating it, but decreased after the unfavorite food. These results suggest a derangement in the ghrelin modulation of food-related pleasurable and rewarding feelings, which might sustain the reduced motivation toward food intake of acute AN patients.

  17. Effects of gastric emptying on the postprandial ghrelin response

    NARCIS (Netherlands)

    Blom, W.A.M.; Lluch, A.; Vinoy, S.; Stafleu, A.; Berg, van den R.; Holst, J.J.; Kok, F.J.; Hendriks, H.F.J.

    2006-01-01

    Distension and chemosensitization of the stomach are insufficient to induce a ghrelin response, suggesting that postgastric feedback is required. This postgastric feedback may be regulated through insulin. We investigated the relation between gastric emptying rate and the postprandial ghrelin respon

  18. Ghrelin and its Association with Nutritional and Inflammatory Status ...

    African Journals Online (AJOL)

    Ghrelin, an orexigenic peptide hormone, ... Ghrelin is a recently identified 28 amino acid peptide hormone ... in patients with chronic kidney disease (CKD). ..... deviation, NS: Nonsignificant, n: Number of subjects, eGFR: Estimated growth factor ...

  19. Associations between serum ghrelin and knee symptoms, joint structures and cartilage or bone biomarkers in patients with knee osteoarthritis.

    Science.gov (United States)

    Wu, J; Wang, K; Xu, J; Ruan, G; Zhu, Q; Cai, J; Ren, J; Zheng, S; Zhu, Z; Otahal, P; Ding, C

    2017-09-01

    The roles of ghrelin in knee osteoarthritis (OA) are unclear. This study aimed to examine cross-sectional associations of ghrelin with knee symptoms, joint structures and cartilage or bone biomarkers in patients with knee OA. This study included 146 patients with symptomatic knee OA. Serum levels of ghrelin and cartilage or bone biomarkers including cartilage oligomeric matrix protein (COMP), cross linked C-telopeptide of type I collagen (CTXI), cross linked N-telopeptide of type I collagen (NTXI), N-terminal procollagen III propeptide (PIIINP), and matrix metalloproteinase (MMP)-3, 10, 13 were measured using Enzyme-linked immunosorbent assay (ELISA). Knee symptoms were assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Infrapatellar fat pad (IPFP) volume, IPFP signal intensity alternation, cartilage defects, bone marrow lesions (BMLs) and effusion-synovitis were assessed using the (MRI). Osteophytes and joint space narrowing (JSN) were assessed using the Osteoarthritis Research Society International atlas. After adjustment for potential confounders, ghrelin quartiles were positively associated with knee symptoms including pain, stiffness, dysfunction and total score (quartile 4 vs 1: β 24.19, 95% CI 8.13-40.25). Ghrelin quartiles were also significantly associated with increased IPFP signal intensity alteration (quartile 4 vs 1: OR 3.57, 95% CI 1.55-8.25) and NTXI, PIIINP, MMP3 and MMP13. Ghrelin was not significantly associated with other joint structures and biomarkers. Serum levels of ghrelin were significantly associated with increased knee symptoms, IPFP signal intensity alteration and serum levels of MMP3, MMP13, NTXI and PIIINP, suggesting that ghrelin may have a role to play in knee OA. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  20. Leptin and ghrelin concentration in hyperthyroid cats before and after radioactive iodine therapy compared to euthyroid control cats.

    Science.gov (United States)

    Marsilio, Sina; Glanemann, Barbara; Martin, Lucile; Szladovits, Balazs; Neiger, Reto

    2017-04-19

    Leptin and ghrelin, two peptide hormones with antagonistic effects on satiety and energy balance, could be involved in the pathogenesis of weight loss and polyphagia in cats with hyperthyroidism. Leptin generally decreases appetite and increases energy expenditure, while ghrelin exerts the opposite effects. Leptin and ghrelin were measured in 42 client owned hyperthyroid cats with a body condition score (BCS) ≤ 5/9 before (T0) and 4 weeks after radioactive iodine treatment (RAIT) (T1). Dependent on the serum total thyroxine concentration concentration at T1, cats were sub-classified as still hyperthyroid (ht-ht) (n = 4), euthyroid (ht-eu) (n = 10) or hypothyroid (ht-hypo) (n = 28). Results were compared to those of 22 healthy, euthyroid control cats with a comparable BCS (≤ 5/9) and age (≥ 8 years) to hyperthyroid cats. At T0, there were no significant differences between hyperthyroid and control cats for leptin (p = 0.06) or ghrelin concentrations (p = 0.27). At T1, leptin significantly decreased in ht-hypo cats compared to T0 (p = 0.0008) despite a significantly increased body weight in this group (p = 0.0001). Serum ghrelin concentrations did not differ between hyperthyroid cats with a history of polyphagia compared to non-polyphagic cats (p = 0.42). After RAIT, ghrelin concentration significantly increased in all hyperthyroid cats (p cats with thyroid dysfunction. Leptin fluctuations occurred independently of body weight in different states of thyroid dysfunction; increasing ghrelin concentrations after RAIT suggest a ghrelin-independent mechanism for polyphagia in hyperthyroid cats.

  1. Carob pulp preparation rich in insoluble dietary fibre and polyphenols increases plasma glucose and serum insulin responses in combination with a glucose load in humans.

    Science.gov (United States)

    Gruendel, Sindy; Otto, Baerbel; Garcia, Ada L; Wagner, Karen; Mueller, Corinna; Weickert, Martin O; Heldwein, Walter; Koebnick, Corinna

    2007-07-01

    Dietary fibre consumption is associated with improved glucose homeostasis. In contrast, dietary polyphenols have been suggested to exert both beneficial and detrimental effects on glucose and insulin metabolism. Recently, we reported that a polyphenol-rich insoluble dietary fibre preparation from carob pulp (carob fibre) resulted in lower postprandial acylated ghrelin levels after a liquid meal challenge test compared with a control meal without supplementation. The effects may, however, differ when a different food matrix is used. Thus, we investigated the effects of carob fibre on glucose, insulin and ghrelin responses in healthy humans in combination with a glucose load. In a randomized single-blind cross-over study involving twenty healthy subjects (aged 22-62 years), plasma glucose, total and acylated ghrelin, and serum insulin were repeatedly assessed before and after the ingestion of 200 ml water with 50 g glucose and 0, 5, 10 or 20 g carob fibre over a period of 180 min. The intake of 5 and 10 g carob fibre increased the plasma glucose by 47 % and 64 % (P carob-enriched glucose solution. Total ghrelin decreased only after 10 g carob fibre (P carob fibre, administered within a water-glucose solution, increases postprandial glucose and insulin responses, suggesting a deterioration in glycaemic control.

  2. Comprehensive Profiling of GPCR Expression in Ghrelin-Producing Cells.

    Science.gov (United States)

    Koyama, Hiroyuki; Iwakura, Hiroshi; Dote, Katsuko; Bando, Mika; Hosoda, Hiroshi; Ariyasu, Hiroyuki; Kusakabe, Toru; Son, Choel; Hosoda, Kiminori; Akamizu, Takashi; Kangawa, Kenji; Nakao, Kazuwa

    2016-02-01

    To determine the comprehensive G protein-coupled receptor (GPCR) expression profile in ghrelin-producing cells and to elucidate the role of GPCR-mediated signaling in the regulation of ghrelin secretion, we determined GPCR expression profiles by RNA sequencing in the ghrelin-producing cell line MGN3-1 and analyzed the effects of ligands for highly expressed receptors on intracellular signaling and ghrelin secretion. Expression of selected GPCRs was confirmed in fluorescence-activated cell-sorted fluorescently tagged ghrelin-producing cells from ghrelin-promoter CreERT2/Rosa-CAG-LSL-ZsGreen1 mice. Expression levels of GPCRs previously suggested to regulate ghrelin secretion including adrenergic-β1 receptor, GPR81, oxytocin receptor, GPR120, and somatostatin receptor 2 were high in MGN3-1 cells. Consistent with previous reports, isoproterenol and oxytocin stimulated the Gs and Gq pathways, respectively, whereas lactate, palmitate, and somatostatin stimulated the Gi pathway, confirming the reliability of current assays. Among other highly expressed GPCRs, prostaglandin E receptor 4 agonist prostaglandin E2 significantly stimulated the Gs pathway and ghrelin secretion. Muscarine, the canonical agonist of cholinergic receptor muscarinic 4, stimulated both the Gq and Gi pathways. Although muscarine treatment alone did not affect ghrelin secretion, it did suppress forskolin-induced ghrelin secretion, suggesting that the cholinergic pathway may play a role in counterbalancing the stimulation of ghrelin by Gs (eg, by adrenaline). In addition, GPR142 ligand tryptophan stimulated ghrelin secretion. In conclusion, we determined the comprehensive expression profile of GPCRs in ghrelin-producing cells and identified two novel ghrelin regulators, prostaglandin E2 and tryptophan. These results will lead to a greater understanding of the physiology of ghrelin and facilitate the development of ghrelin-modulating drugs.

  3. Vagal stimulation modulates inflammation through a ghrelin mediated mechanism in traumatic brain injury

    OpenAIRE

    Bansal, V; Ryu, SY; Lopez, N; Allexan, S; Krzyzaniak, M; Eliceiri, B; Baird, A.; Coimbra, R

    2012-01-01

    Traumatic brain injury (TBI) releases a cascade of inflammatory cytokines. Vagal nerve stimulation (VNS) and ghrelin have known anti-inflammatory effects; furthermore, ghrelin release is stimulated by acetylcholine. We hypothesized VNS decreases post-TBI inflammation through a ghrelin-mediated mechanism. TBI was created in five groups of mice: sham, TBI, TBI/ghrelin, TBI/VNS, and TBI/VNS/ghrelin receptor antagonist (GRa). Serum and tissue ghrelin, and serum TNF-αwere measured. Ghrelin increas...

  4. Acylation type determines ghrelin's effects on energy homeostasis in rodents

    DEFF Research Database (Denmark)

    Heppner, Kristy; Chaudhary, Nilika; Müller, Timo D;

    2012-01-01

    Ghrelin is a gastrointestinal polypeptide that acts through the ghrelin receptor (GHSR) to promote food intake and increase adiposity. Activation of GHSR requires the presence of a fatty-acid (FA) side chain on amino acid residue serine 3 of the ghrelin molecule. However, little is known about th...

  5. Oxytocin and dopamine stimulate ghrelin secretion by the ghrelin-producing cell line, MGN3-1 in vitro.

    Science.gov (United States)

    Iwakura, Hiroshi; Ariyasu, Hiroyuki; Hosoda, Hiroshi; Yamada, Go; Hosoda, Kiminori; Nakao, Kazuwa; Kangawa, Kenji; Akamizu, Takashi

    2011-07-01

    To understand the physiological role of ghrelin, it is crucial to study both the actions of ghrelin and the regulation of ghrelin secretion. Although ghrelin actions have been extensively revealed, the direct factors regulating ghrelin secretion by ghrelin-producing cells (X/A-like cells), however, is not fully understood. In this study, we examined the effects of peptide hormones and neurotransmitters on in vitro ghrelin secretion by the recently developed ghrelin-producing cell line MGN3-1. Oxytocin and vasopressin significantly stimulated ghrelin secretion by MGN3-1 cells. Because MGN3-1 cells express only oxytocin receptor mRNA, not vasopressin receptor mRNA, oxytocin is the likely regulator, with the effect of vasopressin mediated by a cross-reaction. We also discovered that dopamine stimulates ghrelin secretion from MGN3-1 cells in a similar manner to the previously known ghrelin stimulators, epinephrine and norepinephrine. MGN3-1 cells expressed mRNA encoding dopamine receptors D1a and D2. The dopamine receptor D1 agonist fenoldopam stimulated ghrelin secretion, whereas the D2, D3 agonist bromocriptine did not. Furthermore, the D1 receptor antagonist SKF83566 attenuated the stimulatory effect of dopamine. These results indicate that the stimulatory effect of dopamine on ghrelin secretion is mediated by the D1a receptor. In conclusion, we identified two direct regulators of ghrelin, oxytocin and dopamine. These findings will provide new direction for further studies seeking to further understand the regulation of ghrelin secretion, which will in turn lead to greater understanding of the physiological role of ghrelin.

  6. Pathophysiologic basis of anorexia: focus on the interaction between ghrelin dynamics and the serotonergic system.

    Science.gov (United States)

    Takeda, Hiroshi; Nakagawa, Koji; Okubo, Naoto; Nishimura, Mie; Muto, Shuichi; Ohnishi, Shunsuke; Sakamoto, Naoya; Hosono, Hidetaka; Asaka, Masahiro

    2013-01-01

    Anorexia is an important issue in the management of elderly patients with cancer because it contributes to the development of malnutrition, increases morbidity and mortality, and negatively affects patients' quality of life. This review summarizes the potential mechanisms of the development of anorexia in three animal models that mimic the situations commonly seen in elderly patients receiving chemotherapy. Cisplatin-induced anorexia is attributable to a decrease in peripheral and central ghrelin secretion caused by the stimulation of serotonin (5-hydroxytryptamine; 5-HT)2B and 5-HT2C receptors via 5-HT secretion. Age-associated anorexia is caused by an increase in plasma leptin, which results from disturbed reactivity of ghrelin in the hypothalamus and regulation of ghrelin secretion. Environmental change causes the activation of central 5-HT1B and 5-HT2C receptors and the melanocortin-4 receptor system, resulting in a decrease in circulating ghrelin levels which lowers food intake. New therapeutic approaches based on these pathophysiological mechanisms are warranted for the treatment of anorexia in cancer patients, especially elderly ones.

  7. Postprandial ghrelin suppression is exaggerated following major surgery; implications for nutritional recovery

    Directory of Open Access Journals (Sweden)

    Bloom Stephen R

    2007-10-01

    Full Text Available Abstract Meeting patients' nutritional requirements and preventing malnutrition is a challenge following major surgical procedures. The role of ghrelin in nutritional recovery after non-gastrointestinal major surgery is unknown. We used coronary artery bypass grafting (CABG as an example of anticipated good recovery post major surgery. Seventeen patients undergoing CABG (mean ± SEM: 70.1 ± 2.2 yrs, BMI 29.1 ± 1.4 kg/m2, 15 male underwent fasting and postprandial (45 mins after standard test breakfast blood sampling pre-operatively (day 0, post-operatively (day 6 and at follow-up (day 40. Changes in food intake, biochemical and anthropometric markers of nutritional status were recorded. A comparison was made to 17 matched healthy controls (70.6 ± 2.3 yrs, BMI 28.4 ± 1.3 kg/m2. We observed significantly increased post-operative and follow-up fasting ghrelin concentrations compared with pre-operatively (pre-op. 402 ± 42 pmol/L vs post-op. 642 ± 97 pmol/L vs follow-up 603 ± 94 pmol/L (ANOVA p p Our data support the hypothesis that prolonged changes in fasting and postprandial plasma ghrelin concentrations are associated with impaired nutritional recovery after CABG. These findings reinforce the need to investigate ghrelin in other patients groups undergoing major surgery.

  8. Effects of storage time on total protein and globulin concentrations in bovine fresh frozen plasma obtained for transfusion.

    Science.gov (United States)

    Proverbio, D; Spada, E; Baggiani, L; Bagnagatti De Giorgi, G; Roggero, N; Belloli, A; Pravettoni, D; Perego, R

    2015-01-01

    To evaluate the effects of storage conditions on total protein (TP) and globulin fractions in fresh frozen bovine plasma units prepared and stored for transfusion, TP and globulin fractions were evaluated in fresh plasma and at 1 month and 6 and 12 months after blood collection in plasma stored at -20°C. Significant differences in concentrations were found in the median concentration of total protein (P=0.0336), between 0 months and 1 month (P=0.0108), 0 and 6 months (P=0.0023), and 0 and 12 months (P=0.0027), in mean concentration (g/dL) of albumin (P=0.0394), between 0 months and 1 month (P=0.0131), 0 and 6 months (P=0.0035), and 0 and 12 months (P=0.0038), and beta-2 fraction (P=0.0401), between 0 and 6 months (P=0.0401) and 0 and 12 months (P=0.0230). This study suggests that total gamma globulin concentration in bovine frozen plasma is stable for 12 months at -20°C. Total protein, ALB, and beta-2 fraction have significantly different concentrations (g/dL) when compared to prestorage. This study has shown IgG protein fraction stability in bovine fresh frozen plasma collected for transfusion; therefore, bovine fresh frozen plasma seems to be suitable for the treatment of hypogammaglobulinemia (failure of passive transfer) in calves when stored for 12 months at -20°C.

  9. Elevation of Fasting Ghrelin in Healthy Human Subjects Consuming a High-Salt Diet: A Novel Mechanism of Obesity?

    Directory of Open Access Journals (Sweden)

    Yong Zhang

    2016-05-01

    Full Text Available Overweight/obesity is a chronic disease that carries an increased risk of hypertension, diabetes mellitus, and premature death. Several epidemiological studies have demonstrated a clear relationship between salt intake and obesity, but the pathophysiologic mechanisms remain unknown. We hypothesized that ghrelin, which regulates appetite, food intake, and fat deposition, becomes elevated when one consumes a high-salt diet, contributing to the progression of obesity. We, therefore, investigated fasting ghrelin concentrations during a high-salt diet. Thirty-eight non-obese and normotensive subjects (aged 25 to 50 years were selected from a rural community in Northern China. They were sequentially maintained on a normal diet for three days at baseline, a low-salt diet for seven days (3 g/day, NaCl, then a high-salt diet for seven days (18 g/day. The concentration of plasma ghrelin was measured using an immunoenzyme method (ELISA. High-salt intake significantly increased fasting ghrelin levels, which were higher during the high-salt diet (320.7 ± 30.6 pg/mL than during the low-salt diet (172.9 ± 8.9 pg/mL. The comparison of ghrelin levels between the different salt diets was statistically-significantly different (p < 0.01. A positive correlation between 24-h urinary sodium excretion and fasting ghrelin levels was demonstrated. Our data indicate that a high-salt diet elevates fasting ghrelin in healthy human subjects, which may be a novel underlying mechanism of obesity.

  10. Ghrelin suppresses nocturnal secretion of luteinizing hormone (LH) and thyroid stimulating hormone (TSH) in patients with major depression.

    Science.gov (United States)

    Kluge, Michael; Schmidt, Doreen; Uhr, Manfred; Steiger, Axel

    2013-09-01

    Major depression is associated with various endocrine disturbances. Apart from the well-known hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, also the function of the hypothalamic-pituitary-gonadal (HPG) axis and of the hypothalamic-pituitary-thyroid (HPT) axis may be altered compared to healthy subjects. The orexigenic hormone ghrelin is involved in mood regulation and may have antidepressant effects. In addition, it has been shown to suppress secretion of luteinizing hormone (LH) and thyroid stimulating hormone (TSH) in healthy subjects. Aim of this study was therefore to test the effect of ghrelin on the activity of the HPG and HPT axis in patients with major depression. Therefore, secretion profiles of LH and TSH were determined in 14 unmedicated patients with major depression (7 women) twice, receiving 50 μg ghrelin or placebo at 2200, 2300, 0000, and 0100 h. LH secretion after ghrelin injection as assessed by the AUC (4.05 ± 1.18 mlIU min/ml) was significantly (P = 0.049) lower than after placebo injection (4.75 ± 1.33 mlIU min/ml) during the predefined intervention period (2220-0200 h). In addition, LH pulses occurred significantly (P = 0.045) less frequently after ghrelin injection (3.2 ± 1.4) than after placebo injection (3.9 ± 1.7). Mean TSH plasma levels were significantly lower at 0240 h and from 0320 until 0420 h after ghrelin injection than after placebo injection. In conclusion, ghrelin suppressed nocturnal secretion of LH and TSH in patients with major depression. However, these effects were weaker than previously shown in healthy subjects.

  11. Wheat-fibre-induced changes of postprandial peptide YY and ghrelin responses are not associated with acute alterations of satiety

    DEFF Research Database (Denmark)

    Weickert, Martin O; Spranger, Joachim; Holst, Jens Juul

    2006-01-01

    of plasma peptide YY (PYY), serum ghrelin and satiety as secondary outcome measures of a study investigating effects of cereal fibres on parameters of glucose metabolism. Fourteen healthy women were studied on six occasions in a randomized, single-blind, controlled crossover design. After 24 h run...

  12. A novel human ghrelin variant (In1-ghrelin and ghrelin-O-acyltransferase are overexpressed in breast cancer: potential pathophysiological relevance.

    Directory of Open Access Journals (Sweden)

    Manuel D Gahete

    Full Text Available The human ghrelin gene, which encodes the ghrelin and obestatin peptides, contains 5 exons (Ex, with Ex1-Ex4 encoding a 117 amino-acid (aa preproprotein that is known to be processed to yield a 28-aa (ghrelin and/or a 23-aa (obestatin mature peptides, which possess biological activities in multiple tissues. However, the ghrelin gene also encodes additional peptides through alternative splicing or post-translational modifications. Indeed, we previously identified a spliced mRNA ghrelin variant in mouse (In2-ghrelin-variant, which is regulated in a tissue-dependent manner by metabolic status and may thus be of biological relevance. Here, we have characterized a new human ghrelin variant that contains Ex0-1, intron (In 1, and Ex2 and lacks Ex3-4. This human In1-ghrelin variant would encode a new prepropeptide that conserves the first 12aa of native-ghrelin (including the Ser3-potential octanoylation site but has a different C-terminal tail. Expression of In1-variant was detected in 22 human tissues and its levels were positively correlated with those of ghrelin-O-acyltransferase (GOAT; p = 0.0001 but not with native-ghrelin expression, suggesting that In1-ghrelin could be a primary substrate for GOAT in human tissues. Interestingly, levels of In1-ghrelin variant expression in breast cancer samples were 8-times higher than those of normal mammary tissue, and showed a strong correlation in breast tumors with GOAT (p = 0.0001, ghrelin receptor-type 1b (GHSR1b; p = 0.049 and cyclin-D3 (a cell-cycle inducer/proliferation marker; p = 0.009, but not with native-ghrelin or GHSR1a expression. Interestingly, In1-ghrelin variant overexpression increased basal proliferation of MDA-MB-231 breast cancer cells. Taken together, our results provide evidence that In1-ghrelin is a novel element of the ghrelin family with a potential pathophysiological role in breast cancer.

  13. Plasma and erythrocyte glutathione peroxidase activity, serum selenium concentration, and plasma total antioxidant capacity in cats with IRIS stages I-IV chronic kidney disease.

    Science.gov (United States)

    Krofič Žel, M; Tozon, N; Nemec Svete, A

    2014-01-01

    Serum selenium concentrations and the activity of plasma glutathione peroxidase (GPx) decrease with the progression of chronic kidney disease (CKD) in human patients. Selenium is considered a limiting factor for plasma GPx synthesis. Plasma total antioxidant capacity (TAC) is decreased in CKD cats in comparison to healthy cats. Serum selenium concentrations and plasma and erythrocyte GPx activity in cats with CKD are lower than in healthy cats. Serum selenium concentrations, the activity of enzymes, and plasma TAC progressively decrease with the progression of kidney disease according to IRIS (International Renal Interest Society) classification. Twenty-six client-owned cats in IRIS stages I-IV of CKD were compared with 19 client-owned healthy cats. A CBC, serum biochemical profile, urinalysis, plasma and erythrocyte GPx activity, serum selenium concentration, and plasma TAC were measured in each cat. Cats in IRIS stage IV CKD had a significantly higher (P = .025) activity of plasma GPx (23.44 ± 6.28 U/mL) than cats in the control group (17.51 ± 3.75 U/mL). There were no significant differences in erythrocyte GPx, serum selenium concentration, and plasma TAC, either among IRIS stages I-IV CKD cats or between CKD cats and healthy cats. Erythrocyte GPx activity, serum selenium concentration, and plasma TAC do not change in CKD cats compared with healthy cats. Selenium is not a limiting factor in feline CKD. Increased plasma GPx activity in cats with stage IV CKD suggests induction of antioxidant defense mechanisms. Antioxidant defense systems might not be exhausted in CKD in cats. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  14. Plasma zinc antioxidant vitamins, glutathione levels and total antioxidant activity in oral leukoplakia

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    Subhash Chandra Bose

    2012-01-01

    Full Text Available Background: Leukoplakia is a common, potentially premalignant lesion with malignant transformation rate from 1 to 17% with highest transformation rate for the lesions on the floor of the mouth, soft palate and tongue. One of the main etiological factors is consuming areca nut and its commercial preparations which generate high levels of reactive oxygen species during their metabolism. So the aim of this present study is to evaluate the plasma levels of antioxidant vitamins, antioxidant mineral zinc, glutathione and total antioxidant status (TAS in leukoplakia patients. Materials and Methods: For this cross-sectional study, we selected 23 newly diagnosed oral leukoplakia patients of both sexes within the age group 28-40 years and the same number of age and sex matched healthy individuals without having history of any systemic illness were selected as control group. In both the groups, we measured plasma antioxidant vitamins A, C, E, antioxidant mineral zinc, GSH and TAS. Student′s t test was applied and the P value <0.001 was considered as statistically significant. Results: We observed very low levels of antioxidant vitamins A, C, E, antioxidant mineral zinc and antioxidant metabolite GSH (P<0.001 and at the same time we also observed very poor (TAS (P<0.001 in leukoplakia patients when compared to patients in control group. Conclusion: The consumption of tobacco or areca quid which contains high copper levels creates an oxidative stress like environment during their metabolism, might play a major role in causation and propagation of oral leukoplakia.

  15. Characterization of adult ghrelin and ghrelin receptor knockout mice under positive and negative energy balance.

    Science.gov (United States)

    Sun, Yuxiang; Butte, Nancy F; Garcia, Jose M; Smith, Roy G

    2008-02-01

    Ghrelin and the ghrelin receptor (GH secretagogue receptor, GHS-R), are believed to have important roles in energy homeostasis. We describe results from the first studies to be conducted in congenic (N10) adult ghrelin(-/-) and Ghsr(-/-) mice under conditions of both positive (high-fat diet) and negative (caloric restriction) energy balance. In contrast to results from young N2 mutant mice, changes in body weight and energy expenditure are not clearly distinguishable across genotypes. Although respiratory quotient was lower in mice fed a high-fat diet, no differences were evident between littermate wild-type and null genotypes. With normal chow, a modest decrease trend in respiratory quotient was detected in ghrelin(-/-) mice but not in Ghsr(-/-) mice. Under caloric restriction, the weight loss of ghrelin(-/-) and Ghsr(-/-) mice was identical to wild-type littermates, but blood glucose levels were significantly lower. We conclude that adult congenic ghrelin(-/-) and Ghsr(-/-) mice are not resistant to diet-induced obesity but under conditions of negative energy balance show impairment in maintaining glucose homeostasis. These results support our hypothesis that the primary metabolic function of ghrelin in adult mice is to modulate glucose sensing and insulin sensitivity, rather than directly regulate energy intake and energy expenditure.

  16. Adipokines and ghrelin in gastric cancer cachexia

    Institute of Scientific and Technical Information of China (English)

    Mustafa Kerem; Zafer Ferahkose; Utku Tonguc Yilmaz; Hatice Pasaoglu; Ebru Ofluoglu; Abdulkadir Bedirli; Bulent Salman; Tevfik Tolga Sahin; Murat Akin

    2008-01-01

    AIM: To investigate the roles of the adipocytokines, ghrelin and leptin in gastric cancer cachexia.METHODS: Resistin, ghrelin, leptin, adiponectin, insulin and insulin-like growth factor (IGF-I), were measured in 30 healthy subjects, and 60 gastric cancer patients of which 30 suffered from cancer- induced cachexia and 30 served as a control group. The relationships between hormones, body mass index (BMI) loss ratio, age, gender, and Glasgow Prognostic Score (GPS) were investigated.RESULTS: Cachexia patients had higher tumor stage and GPS when compared with non-cachexia patients (P<0.05). Ghrelin, resistin, leptin, adiponectin and IGF-I, showed a significant correlation with BMI loss ratio and GPS (P < 0.05). A strong correlation was seen between GPS and BMI loss (R = -0.570, P < 0.0001). Multivariate analysis indicated that BMI loss was significantly independent as a predictor of ghrelin, resistin, leptin and IGF-I (P<0.05). Existence of an important significant relationship between resistin and insulin resistance was also noted.CONCLUSION: These results showed that serum ghrelin, leptin, adiponectin, and IGF-I play important roles in cachexia-related gastric cancers. No relationship was found between resistin and cancer cachexia. Also, because of the correlation between these parameters and GPS, these parameters might be used as a predictor factor.

  17. Circulating ghrelin level is higher in HNF1A-MODY and GCK-MODY than in polygenic forms of diabetes mellitus.

    Science.gov (United States)

    Nowak, Natalia; Hohendorff, Jerzy; Solecka, Iwona; Szopa, Magdalena; Skupien, Jan; Kiec-Wilk, Beata; Mlynarski, Wojciech; Malecki, Maciej T

    2015-12-01

    Ghrelin is a hormone that regulates appetite. It is likely to be involved in the pathophysiology of varying forms of diabetes. In animal studies, the ghrelin expression was regulated by the hepatocyte nuclear factor 1 alpha (HNF1A). Mutations of the HNF1A gene cause maturity onset diabetes of the young (MODY). We aimed to assess the circulating ghrelin levels in HNF1A-MODY and in other types of diabetes and to evaluate its association with HNF1A mutation status. Our cohort included 46 diabetic HNF1A gene mutation carriers, 55 type 2 diabetes (T2DM) subjects, 42 type 1 diabetes (T1DM) patients, and 31 glucokinase (GCK) gene mutation carriers with diabetes as well as 51 healthy controls. Plasma ghrelin concentration was measured using the immunoenzymatic assay with polyclonal antibody against the C-terminal fragment of its acylated and desacylated forms. Ghrelin concentrations were 0.75 ± 0.32, 0.70 ± 0.21, 0.50 ± 0.20, and 0.40 ± 0.16 ng/ml in patients with HNF1A-MODY, GCK-MODY, T1DM, and T2DM, respectively. The ghrelin levels were higher in HNF1A-MODY and GCK-MODY than in T1DM and T2DM (p diabetic controls (1.02 ± 0.29 ng/ml, p MODY groups and common diabetes types remained significant. Analysis by a HNF1A mutation type indicated that ghrelin concentration is similar in patients with different types of sequence differences. Plasma ghrelin level is higher in HNF1A-MODY and GCK-MODY than in the common polygenic forms of diabetes.

  18. Shifting the circadian rhythm of feeding in mice induces gastrointestinal, metabolic and immune alterations which are influenced by ghrelin and the core clock gene Bmal1.

    Science.gov (United States)

    Laermans, Jorien; Broers, Charlotte; Beckers, Kelly; Vancleef, Laurien; Steensels, Sandra; Thijs, Theo; Tack, Jan; Depoortere, Inge

    2014-01-01

    In our 24-hour society, an increasing number of people are required to be awake and active at night. As a result, the circadian rhythm of feeding is seriously compromised. To mimic this, we subjected mice to restricted feeding (RF), a paradigm in which food availability is limited to short and unusual times of day. RF induces a food-anticipatory increase in the levels of the hunger hormone ghrelin. We aimed to investigate whether ghrelin triggers the changes in body weight and gastric emptying that occur during RF. Moreover, the effect of genetic deletion of the core clock gene Bmal1 on these physiological adaptations was studied. Wild-type, ghrelin receptor knockout and Bmal1 knockout mice were fed ad libitum or put on RF with a normal or high-fat diet (HFD). Plasma ghrelin levels were measured by radioimmunoassay. Gastric contractility was studied in vitro in muscle strips and in vivo (13C breath test). Cytokine mRNA expression was quantified and infiltration of immune cells was assessed histologically. The food-anticipatory increase in plasma ghrelin levels induced by RF with normal chow was abolished in HFD-fed mice. During RF, body weight restoration was facilitated by ghrelin and Bmal1. RF altered cytokine mRNA expression levels and triggered contractility changes resulting in an accelerated gastric emptying, independent from ghrelin signaling. During RF with a HFD, Bmal1 enhanced neutrophil recruitment to the stomach, increased gastric IL-1α expression and promoted gastric contractility changes. This is the first study demonstrating that ghrelin and Bmal1 regulate the extent of body weight restoration during RF, whereas Bmal1 controls the type of inflammatory infiltrate and contractility changes in the stomach. Disrupting the circadian rhythm of feeding induces a variety of diet-dependent metabolic, immune and gastrointestinal alterations, which may explain the higher prevalence of obesity and immune-related gastrointestinal disorders among shift workers.

  19. Shifting the circadian rhythm of feeding in mice induces gastrointestinal, metabolic and immune alterations which are influenced by ghrelin and the core clock gene Bmal1.

    Directory of Open Access Journals (Sweden)

    Jorien Laermans

    Full Text Available BACKGROUND: In our 24-hour society, an increasing number of people are required to be awake and active at night. As a result, the circadian rhythm of feeding is seriously compromised. To mimic this, we subjected mice to restricted feeding (RF, a paradigm in which food availability is limited to short and unusual times of day. RF induces a food-anticipatory increase in the levels of the hunger hormone ghrelin. We aimed to investigate whether ghrelin triggers the changes in body weight and gastric emptying that occur during RF. Moreover, the effect of genetic deletion of the core clock gene Bmal1 on these physiological adaptations was studied. METHODS: Wild-type, ghrelin receptor knockout and Bmal1 knockout mice were fed ad libitum or put on RF with a normal or high-fat diet (HFD. Plasma ghrelin levels were measured by radioimmunoassay. Gastric contractility was studied in vitro in muscle strips and in vivo (13C breath test. Cytokine mRNA expression was quantified and infiltration of immune cells was assessed histologically. RESULTS: The food-anticipatory increase in plasma ghrelin levels induced by RF with normal chow was abolished in HFD-fed mice. During RF, body weight restoration was facilitated by ghrelin and Bmal1. RF altered cytokine mRNA expression levels and triggered contractility changes resulting in an accelerated gastric emptying, independent from ghrelin signaling. During RF with a HFD, Bmal1 enhanced neutrophil recruitment to the stomach, increased gastric IL-1α expression and promoted gastric contractility changes. CONCLUSIONS: This is the first study demonstrating that ghrelin and Bmal1 regulate the extent of body weight restoration during RF, whereas Bmal1 controls the type of inflammatory infiltrate and contractility changes in the stomach. Disrupting the circadian rhythm of feeding induces a variety of diet-dependent metabolic, immune and gastrointestinal alterations, which may explain the higher prevalence of obesity and

  20. Circulating motilin, ghrelin, and GLP-1 and their correlations with gastric slow waves in patients with chronic kidney disease.

    Science.gov (United States)

    Wu, Gao-Jue; Cai, Xu-Dong; Xing, Jie; Zhong, Guang-Hui; Chen, Jiande D Z

    2017-08-01

    Patients with chronic kidney disease (CKD) commonly complain upper gastrointestinal (GI) symptoms, especially anorexia. Hemodialysis (HD) has been noted to improve GI symptoms; however, the underlying mechanisms are unclear. This study was designed 1) to study effects of HD on GI symptoms and gastric slow waves; and 2) to investigate possible roles of ghrelin and glucagon-like peptide-1 (GLP-1): the study recruited 13 healthy controls, 20 CKD patients without HD (CKD group), and 18 CKD patients with HD (HD group). Dyspeptic symptoms, autonomic functions, gastric slow waves, and plasma level of ghrelin and GLP-1 were analyzed. First, the CKD patients with HD showed markedly lower scores of anorexia (0.6 ± 0.2 vs. 3.2 ± 0.4, P waves, compared with controls. Third, the CKD group exhibited a significantly lower ghrelin level compared with the HD group (26.8 ± 0.9 vs. 34.1 ± 2.3 ng/l, P waves was positively correlated with ghrelin (r = 0.385, P = 0.019) but negatively correlated with GLP-1 (r = -0.558, P waves in CKD patients. An increase in ghrelin and a decrease in GLP-1 might be involved in the HD-induced improvement in gastric slow waves. Copyright © 2017 the American Physiological Society.

  1. Ghrelin function in insulin release and glucose metabolism.

    Science.gov (United States)

    Dezaki, Katsuya

    2013-01-01

    Given its wide spectrum of biological activities such as growth hormone (GH) release, feeding stimulation, adiposity and cardiovascular actions, the discovery of ghrelin opened many new perspectives within neuroendocrine, metabolic and cardiovascular research, thus suggesting its possible clinical application. Circulating ghrelin is produced predominantly in the stomach, and its receptor GH secretagogue receptor (GHS-R) is expressed in a variety of central and peripheral tissues. Ghrelin, GHS-R and ghrelin O-acyltransferase (GOAT), the enzyme that promotes the acylation of the third serine residue of ghrelin, are all expressed in pancreatic islets, and this peptide is released into pancreatic microcirculations. Ghrelin inhibits insulin release in mice, rats and humans. The signal transduction mechanisms of ghrelin receptor in islet β-cells are very unique, being distinct from those utilized for GH release. Pharmacological and genetic blockade of islet-derived ghrelin markedly augments glucose-induced insulin release in vitro. Ablation of ghrelin, GHS-R or GOAT enhances insulin release and prevents impaired glucose tolerance in high-fat, diet-induced and leptin-deficient obese models. Thus, manipulation of the insulinostatic function of the ghrelin-GHS-R system, particularly that in islets, could optimize the amount of insulin release to meet the systemic demand. Ghrelin antagonism provides a novel strategy to treat type 2 diabetes with dysregulated insulin release.

  2. Ghrelin's second life: From appetite stimulator to glucose regulator

    Institute of Scientific and Technical Information of China (English)

    Pieter-Jan Verhulst; Inge Depoortere

    2012-01-01

    Ghrelin,a 28 amino acid peptide hormone produced by the stomach,was the first orexigenic hormone to be discovered from the periphery.The octanoyl modification at Ser3,mediated by ghrelin O-acyltransferase (GOAT),is essential for ghrelin's biological activity.Ghrelin stimulates food intake through binding to its receptor (GRLN-R) on neurons in the arcuate nucleus of the hypothalamus.Ghrelin is widely expressed throughout the body; accordingly,it is implicated in several other physiological functions,which include growth hormone release,gastric emptying,and body weight regulation.Ghrelin and GRLN-R expression are also found in the pancreas,suggesting a local physiological role.Accordingly,several recent studies now point towards an important role for ghrelin and its receptor in the regulation of blood glucose homeostasis,which is the main focus of this review.Several mechanisms of this regulation by ghrelin have been proposed,and one possibility is through the regulation of insulin secretion.Despite some controversy,most studies suggest that ghrelin exerts an inhibitory effect on insulin secretion,resulting in increased circulating glucose levels.Ghrelin may thus be a diabetogenic factor.Obesity-related type 2 diabetes has become an increasingly important health problem,almost reaching epidemic proportions in the world; therefore,antagonists of the ghrelin-GOAT signaling pathway,which will tackle both energy-and glucose homeostasis,may be considered as promising new therapies for this disease.

  3. Effects of exercise in the cold on Ghrelin, PYY, and food intake in overweight adults.

    Science.gov (United States)

    Crabtree, Daniel R; Blannin, Andrew K

    2015-01-01

    Exercise in cold water has been shown to simulate postexercise energy intake (EI) in normal-weight individuals. However, the effect of cold exercise on EI in overweight individuals has yet to be examined. The present study investigated the effect of brisk walking in a cold (8°C) and neutral (20°C) environment on postexercise EI and appetite hormone responses. Sixteen overweight participants (10 men and six women; age, 50.1 ± 11.6 yr; body mass index, 28.9 ± 4.2 kg·m) completed a 45-min treadmill walk at 8°C and 20°C in a randomized counterbalanced design. Participants were presented with an ad libitum buffet meal 45 min after exercise, and EI was covertly measured. Skin and rectal temperature were monitored throughout exercise and for 30 min after exercise, and concentrations of the appetite hormones total ghrelin, acylated ghrelin, and total peptide YY were assessed before and after exercise and before and after meal. EI was significantly greater after exercise in the cold (1299 ± 657 kcal (mean ± SD)) compared with that after exercise in the neutral environment (1172 ± 537 kcal (mean ± SD)) (P ghrelin concentrations and the acylated ghrelin AUC values were significantly greater during walking in the cold versus those during walking in the neutral condition (P exercise in the cold stimulates postexercise EI to a greater extent than exercise in a neutral environment.

  4. The effect of whisky and wine consumption on total phenol content and antioxidant capacity of plasma from healthy volunteers

    DEFF Research Database (Denmark)

    Duthie, GG; Pedersen, M W; PC, Morrice

    1998-01-01

    OBJECTIVE: To assess whether consumption of 100 ml of whisky or red wine by healthy male subjects increasedplasma total phenol content and antioxidant capacity. DESIGN: A Latin square arrangement to eliminate ordering effectswhereby, after an overnight fast, nine volunteers consumed 100 ml of red....... RESULTS: Within 30 min of consumption of the wine and whisky, there was a similar andsignificant increase in plasma total phenol content and antioxidant capacity as determined by the ferric reducing capacityof plasma (FRAP). No changes were observed following consumption of 'new make' spirit. CONCLUSIONS......:Consumption of phenolic-containing alcoholic beverages transiently raises total phenol concentration and enhances theantioxidant capacity of plasma. This is compatible with suggestions that moderate alcohol usage and increasedantioxidant intake decrease the risk of coronary heart disease....

  5. Obesity Impairs the Action of the Neuroendocrine Ghrelin System.

    Science.gov (United States)

    Zigman, Jeffrey M; Bouret, Sebastien G; Andrews, Zane B

    2016-01-01

    Ghrelin is a metabolic hormone that promotes energy conservation by regulating appetite and energy expenditure. Although some studies suggest that antagonizing ghrelin function attenuates body weight gain and glucose intolerance on a high calorie diet, there is little information about the metabolic actions of ghrelin in the obese state. In this review, we discuss the novel concept of obesity-induced central ghrelin resistance in neural circuits regulating behavior, and impaired ghrelin secretion from the stomach. Interestingly, weight loss restores ghrelin secretion and function, and we hypothesize that ghrelin resistance is a mechanism designed to protect a higher body weight set-point established during times of food availability, to maximize energy reserves during a time of food scarcity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. The Antidepressant-like Effects of Estrogen-mediated Ghrelin

    Science.gov (United States)

    Wang, Pu; Liu, Changhong; Liu, Lei; Zhang, Xingyi; Ren, Bingzhong; Li, Bingjin

    2015-01-01

    Ghrelin, one of the brain-gut peptides, stimulates food-intake. Recently, ghrelin has also shown to play an important role in depression treatment. However, the mechanism of ghrelin’s antidepressant-like actions is unknown. On the other hand, sex differences in depression, and the fluctuation of estrogens secretion have been proved to play a key role in depression. It has been reported that women have higher level of ghrelin expression, and ghrelin can stimulate estrogen secretion while estrogen acts as a positive feedback mechanism to up-regulate ghrelin level. Ghrelin may be a potential regulator of reproductive function, and estrogen may have additional effect in ghrelin’s antidepressantlike actions. In this review, we summarize antidepressant-like effects of ghrelin and estrogen in basic and clinical studies, and provide new insight on ghrelin’s effect in depression. PMID:26412072

  7. Is Ghrelin Synthesized in the Central Nervous System?

    Science.gov (United States)

    Cabral, Agustina; López Soto, Eduardo J.; Epelbaum, Jacques; Perelló, Mario

    2017-01-01

    Ghrelin is an octanoylated peptide that acts via its specific receptor, the growth hormone secretagogue receptor type 1a (GHSR-1a), and regulates a vast variety of physiological functions. It is well established that ghrelin is predominantly synthesized by a distinct population of endocrine cells located within the gastric oxyntic mucosa. In addition, some studies have reported that ghrelin could also be synthesized in some brain regions, such as the hypothalamus. However, evidences of neuronal production of ghrelin have been inconsistent and, as a consequence, it is still as a matter of debate if ghrelin can be centrally produced. Here, we provide a comprehensive review and discussion of the data supporting, or not, the notion that the mammalian central nervous system can synthetize ghrelin. We conclude that no irrefutable and reproducible evidence exists supporting the notion that ghrelin is synthetized, at physiologically relevant levels, in the central nervous system of adult mammals. PMID:28294994

  8. Total plasma homocysteine and methylenetetrahydrofolate reductase C677T polymorphism in patients with colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Sandra Battistelli; Aurelio Vittoria; Massimo Stefanoni; Camilla Bing; Franco Roviello

    2006-01-01

    AIM: To investigate the behaviour of total plasma homocysteine (tHcy) and its most common genetic determinant defect, the methylenetetrahydrofolate reductase C677T (C677TMTHFR) polymorphism in patients with early stage colorectal carcinoma.METHODS: tHcy was quantified by Abbott IMx immunoassay; screening for C677TMTHFR substitution was performed by PCR and restriction analysis.RESULTS: The frequency of the C/T and T/T genotypes of the C677TMTHFR gene polymorphism did not differ between the groups. The mean tHcy was statistically higher in cancer patients than in control subjects carrying the same C/C or C/T genotype, whereas there was no difference in the T/T homozygous carriers of the two groups. tHcy was significantly higher in the T/T homozygous carriers than in C/C and C/T genotype carriers.CONCLUSION: The statistically significant increase of tHcy observed in C/C and C/T genotype carriers among our cancer patients is related to substrate consumption dependent on the tumor cell proliferation rate, whereas the tHcy increase observed in T/T genotype carriers of both groups probably depends on the enzymatic deficit of the homocysteine conversion to methionine and/or on the folate deficiency.

  9. Proteomic analysis of plasma from rats following total parenteral nutrition-induced liver injury.

    Science.gov (United States)

    Tsai, Jai-Jen; Kuo, Hsing-Chun; Lee, Kam-Fai; Tsai, Tung-Hu

    2015-11-01

    Total parenteral nutrition (TPN) is provided as the primary nitrogen source to manage patients with intestinal failure who were not able to sustain themselves on enteral feeds. The most common complication of long-term TPN use is hepatitis. A proteomic approach was used to identify proteins that are differentially expressed in the plasma of rats following TPN-related acute liver injury. Six male rats were randomly assigned to either the saline infusion control group or the TPN infusion group. Our results demonstrate that TPN infusion in rats resulted in hepatic dysfunction and hepatocyte apoptosis. Five proteins that were differentially expressed between TPN infusion and normal rats were determined and validated in vivo. Fascinatingly, the proteomic differential displays, downregulated proteins included peroxiredoxin 2 (PRDX2), alpha-1-antiproteinase (A1AT), and fibrinogen gamma chain (FIBG), which were involved in oxidative stress, inflammatory respondence and cells apoptosis. After TPN infusion, two protein spots showed increased expression, namely, the glucagon receptor (GLR) protein and apolipoprotein A-1 (APOA1), which may mediate the effects of TPN administration on glycogen and lipid metabolism. In this study, proteomic analysis suggested TPN-related acute liver injury could be involved in limiting cellular protection mechanisms against oxidative stress-induced apoptosis. On the basis of the results, we also give molecular evidences replying TPN-related hepatitis.

  10. Maternal serum ratio of ghrelin to obestatin decreased in preeclampsia.

    Science.gov (United States)

    Wu, Weiguang; Fan, Xiaobin; Yu, Yuecheng; Wang, Yingchun

    2015-10-01

    Ghrelin, an endogenous for the growth hormone secretagogue receptor, has been shown to participate in blood pressure regulation. Obestatin, encoded by the same gene as ghrelin, is described as a physiological opponent of ghrelin. We hypothesized that ghrelin/obestatin imbalance played a role in the pathogenesis. This study was designed to determine the alterations of ghrelin and obestatin concentrations and ghrelin/obestatin ratio in maternal serum in preeclampsia. This retrospective case-control study included 31 preeclampsia and 31 gestational week-matched normal pregnancies. Ghrelin and obestatin concentrations in maternal serum were determined by radioimmunoassay, and the ghrelin/obestatin ratio was calculated. The ghrelin concentration and ghrelin/obestatin ratio in maternal serum were significantly lower in preeclampsia than in normal pregnancies (214.34±14.27pg/mL vs 251.49±16.15pg/mL, P=0.041, 1.07±0.09 vs 0.82±0.08, P=0.023). The obestatin concentration in maternal serum was significantly higher in preeclampsia than in normal pregnancies (276.35±15.38pg/mL vs 223.53±18.61pg/mL, P=0.019). The systolic blood pressure in preeclampsia was negatively correlated with ghrelin concentration and ghrelin/obestatin ratio (r=-0.549, P=0.003; r=-0.491, P=0.004) and was positively correlated with obestatin concentrations in preeclampsia (r=0.388, P=0.013). The findings of this study suggested disturbance of ghrelin and obestatin in maternal serum in preeclampsia, and ghrelin/obestatin imbalance might play a role in the pathogenesis of preeclampsia. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

  11. Rikkunshito ameliorates cachexia associated with bleomycin-induced lung fibrosis in mice by stimulating ghrelin secretion.

    Science.gov (United States)

    Tsubouchi, Hironobu; Yanagi, Shigehisa; Miura, Ayako; Mogami, Sachiko; Yamada, Chihiro; Iizuka, Seiichi; Hattori, Tomohisa; Nakazato, Masamitsu

    2014-10-01

    Cachexia is a frequent complication in patients with respiratory failure, such as lung fibrosis, and it is a determining factor for functional capacity, health status, and mortality. Reductions in body weight and skeletal muscle mass are key features of cachexia that are resistant to current therapies. Rikkunshito (RKT), a traditional Japanese herbal medicine, is widely used for the treatment for patients with gastrointestinal symptoms and known to stimulate ghrelin secretion. By using bleomycin (BLM)-induced lung fibrosis mice in this study, we tested our hypothesis that RKT administration could ameliorate pulmonary cachexia. After BLM administration, mice were provided with either RKT or distilled water on a daily basis. Compared with the BLM-injected mice, the RKT-treated mice had smaller reductions of food intake and body weight. Skeletal muscle weights were retained in the RKT-treated mice, in conjunction with reduced expressions of MuRF-1 and atrogin-1 in the lysates of skeletal muscle found in lung fibrosis. Rikkunshito administration restored the plasma concentrations of ghrelin in BLM-injected mice. The anticachectic efficacies of RKT administration in BLM-injected mice were canceled by the concurrent treatment of a ghrelin receptor antagonist. Rikkunshito administration did not decrease the degree of loss of body weight or food intake reduction in either ghrelin-deficient mice or growth hormone secretagogue receptor-deficient mice. Our results indicate that RKT administration exerts protective effects on pulmonary cachexia by ameliorating skeletal muscle wasting and food intake reduction as mediated by the ghrelin system and, thus, highlight RKT as a potential therapeutic agent for the management of lung fibrosis.

  12. Expression of ghrelin and insulin-like growth factor-1 in immature piglet model of chronic cyanotic congenital heart defects with decreased pulmonary blood flow

    Institute of Scientific and Technical Information of China (English)

    WANG Dong; LIU Ying-long; L(U) Xiao-dong; ZHU Yao-bin; LING Feng; LIU Ai-jun; LI Gang; XU Yu-lin

    2011-01-01

    Background Cyanotic patients have potential growth retardation and malnutrition due to hypoxemia and other reasons.Ghrelin is a novel endogenous growth hormone secretagogue that has effects on growth and cardiovascular activities.The aim of this study was to evaluate the plasma level and myocardial expression of ghrelin and insulin-like growth factor-1 (IGF-1) using an immature piglet model of chronic cyanotic congenital heart defects with decreased pulmonary blood flow. Methods Twelve weanling Chinese piglets underwent procedures of main pulmonary artery-left atrium shunt with pulmonary artery banding or sham operation as control. Four weeks later, hemodynamic parameters were measured.Enzyme-linked immunosorbent assay for plasma ghrelin and IGF-1 level measurement were performed. Ventricular ghrelin and IGF-1 mRNA expressions were measured by quantitative real-time polymerase chain reaction. Results Four weeks after surgical procedure, the cyanotic model produced lower arterial oxygen tension ((68.73 ±15.09) mmHg), arterial oxygen saturation ((82.35 ± 8.63)%), and higher arterial carbon dioxide tension ((51.83 ± 6.12)mmHg), hematocrit ((42.67 ± 3.83)%) and hemoglobin concentration ((138.17 ± 16.73) g/L) than the control piglets ((194.08 ± 98.79) mmHg, (96.43 ± 7.91)%, (36.9 ± 4.73) mmHg, (31.17 ± 3.71)%, (109.83 ± 13.75) g/L) (all P <0.05).Plasma ghrelin level was significantly higher in the cyanotic model group in comparison to the control (P=0.004), and the plasma IGF-1 level was significantly lower than control (P=0.030). Compared with control animals, the expression of ghrelin mRNAs in the ventricular myocardium was significantly decreased in the cyanotic model group (P=0.000), and the expression of IGF-1 mRNAs was elevated (P=0.001). Conclusions Chronic cyanotic congenital heart defects model was successfully established. Plasma ghrelin level and myocardial IGF-1 mRNA expression were significantly up-regulated, while plasma IGF-1 level and

  13. Anti-ghrelin antibodies in appetite suppression: recent advances in obesity pharmacotherapy

    Directory of Open Access Journals (Sweden)

    Altabas V

    2015-07-01

    Full Text Available Velimir Altabas, Vanja Zjačić-Rotkvić Department of Endocrinology, Diabetes and Metabolic Diseases, “Mladen Sekso”, Clinic for Internal Medicine, University Hospital Center “Sestre milosrdnice”, Zagreb, Croatia Abstract: Obesity is a medical condition caused by accumulated excess body fat with negative impact on patients' health, including decreased life expectancy. It has become a major health problem in most developed and developing countries, since the worldwide prevalence of obesity nearly doubled during the last 30 years. Consequently, novel treatments focusing on obesity are being investigated. Potential targets include several pathophysiological mechanisms involved in appetite control affecting multiple organ systems, like adipose tissue; some cell types in the stomach and gut; pancreas; thyroid gland; several hypothalamic areas; and centers located in the brainstem. One of the most important orexigenic neuropeptides is ghrelin, which is produced and secreted primarily by ghrelin cells located in the stomach and duodenum. In humans, plasma ghrelin levels rise when the stomach is empty and fall shortly after meal ingestion. In fat tissue, ghrelin increases fat storage. In the brain, it exerts its orexigenic action through activation of NPY/AgRP neurons in the arcuate nucleus. From the pharmacological point of view, it seems that opposing ghrelin activity could be used as a therapeutic principle in treating obesity. The principal idea of antiobesity drugs is to augment anorexigenic and lipolytic signaling, or to block orexigenic and lipogenic mediators. Recent studies have shown that therapeutic vaccines could be a new approach in the development of antiobesity medications. A vaccine should provoke an immune response to a specific causal factor for a particular disease. Several types of anti-ghrelin vaccines have been developed so far, with significant immune response in terms of rising anti-ghrelin antibodies. However, in the

  14. Ghrelin O-acyltransferase (GOAT), a specific enzyme that modifies ghrelin with a medium-chain fatty acid.

    Science.gov (United States)

    Kojima, Masayasu; Hamamoto, Akie; Sato, Takahiro

    2016-10-01

    In the gastric peptide hormone ghrelin, serine 3 (threonine 3 in frogs) is modified, primarily by n-octanoic acid; this modification is essential for ghrelin's activity. The enzyme that transfers n-octanoic acid to Ser3 of ghrelin is ghrelin O-acyltransferase (GOAT). GOAT, the only enzyme known to catalyze acyl modification of ghrelin, specifically modifies serine (or threonine) at the third position and does not modify other serine residues in ghrelin peptides. GOAT prefers n-hexanoyl-CoA over n-octanoyl-CoA as the acyl donor, although in the stomach the n-octanoyl form is the predominant form of acyl-modified ghrelin. GOAT is a promising target for drug development to treat metabolic diseases and eating disorders.

  15. Increase in plasma total antioxidant capacity of grazing Japanese Black heifers and cows in forestland in Japan.

    Science.gov (United States)

    Haga, Satoshi; Ishizaki, Hiroshi; Nakano, Miwa; Nakao, Seiji; Hirano, Kiyoshi; Yamamoto, Yoshito; Kitagawa, Miya; Sasaki, Hiroyuki; Kariya, Yoshihiro

    2014-02-01

    Blood total antioxidant capacity (TAC) has become a key bio-marker for animal health. Forest-grazing cattle are known to forage various native plants that have high TAC. This study evaluated differences of plasma TAC between forest-grazing (FG) and pasture-grazing cattle (PG). Experiment 1 monitored the plasma TAC levels of 32 Japanese Black cattle. The level in PG did not change throughout the grazing period. However, that in FG, which increased from summer, was significantly higher than that in PG through fall (P antioxidant parameters and the TAC in plants that the cattle consumed in late June and September. The plasma TAC levels in FG were significantly higher than those in PG in both periods (P pasture grasses. Results of this study show that plasma TAC of grazing Japanese Black cattle in forestland increase from summer through fall.

  16. Total plasma clearance versus urinary plasma clearance of (51)Cr-EDTA in patients with cirrhosis with and without fluid retention

    DEFF Research Database (Denmark)

    Henriksen, Ulrik Lütken; Hansen, Hanne B; Ring-Larsen, Helmer

    2015-01-01

    Abstract Background and aim. In patients with fluid retention, the total plasma clearance of (51)Cr-EDTA (ClP) may overestimate the glomerular filtration rate (GFR). The present study was therefore undertaken in order to compare ClP with the urinary plasma clearance of (51)Cr-EDTA (ClU) in patients...... with cirrhosis with and without fluid retention. Material and methods. A total of 136 patients with cirrhosis (24 without fluid retention, 112 with ascites) received a quantitative intravenous injection of (51)Cr-EDTA followed by plasma and quantitative urinary samples for 5 hours. ClP was determined from...... the injected dose relative to the plasma concentration-time area, extrapolated to infinity. ClU was determined as urinary excretion relative to the plasma concentration-time area up to voiding. Results. In patients without fluid retention, the difference between ClP and ClU (ClP - ClU = ClΔ) was mean 4.5 m...

  17. Role of ghrelin and leptin in the regulation of carbohydrate metabolism. Part I. Ghrelin 

    Directory of Open Access Journals (Sweden)

    Ewa Otto-Buczkowska

    2012-10-01

    Full Text Available Ghrelin is a polypeptide that is excreted by the secretory cells of the gastric and intestinal mucosa, the arcuate nucleus of the hypothalamus as well as by the epsilon cells (ε located in the pancreatic islets. It plays an important role in maintaining the energy balance of the organism and influences the endocrine function of the pancreas and glucose metabolism. It takes part in the regulation of glucose homeostasis through the modulation of insulin secretion and insulin sensitivity.Due to the broad spectrum of ghrelin’s biological effects, ways to modify them are presently being investigated. Much attention is focused on the enzyme called ghrelin O-acyl transferase (GOAT, which mediates the physiological functions of ghrelin. Acyl-ghrelin and des-acyl-ghrelin appear to have opposite glucoregulatory effects. The regulation of acylation by GOAT seems therefore to play a role in mediating glucose metabolism. The modulation of GOAT or ghrelin signaling may be a clinically relevant strategy to treat obesity and metabolic diseases such as type 2 diabetes. 

  18. X-ray plasma diagnostics for totally and partially photoionized plasmas such as warm absorbers in agn

    Directory of Open Access Journals (Sweden)

    Delphine Porquet

    2000-01-01

    Full Text Available Gracias a la nueva generaci on de satelites de rayos-X, como Chandra y XMM, se pueden obtener espectros de alta sensibilidad y resoluci on. En particular, se pueden separar las tres l neas m as intensas (resonantes, de intercombinaci on y prohibidas de iones de baja carga (baja Z como el He, en plasmas no solares. Basados en estas tres l neas, presentamos diagn osticos para densidad, procesos de ionizaci on y temperatura totalmente o parcialmente ionizados por fotoionizaci on. Estos poderosos diagn osticos pueden ser usados en plasmas calientes como los de AGN, galaxias con brotes de formaci on estelar, binarias de rayos-X, etc. En parti- cular, pueden ser usados en los absorbedores tibios que se ven en AGN (Porquet & Dubau 2000, que son herramientas importantes para entender las regiones centrales de diferentes tipos de AGN (Seyferts 1 y 2 y cuasares de bajo y alto corrimiento al rojo.

  19. IFCC reference measurement procedure for substance concentration determination of total carbon dioxide in blood, plasma or serum

    NARCIS (Netherlands)

    Burnett, RW; Covington, AK; Fogh-Andersen, N; Kulpmann, WR; Lewenstam, A; Mas, AHJ; VanKessel, AL; Zijlstra, WG

    2001-01-01

    A reference measurement procedure for substance concentration determination of total CO, in blood, plasma (the anticoagulant is usually heparin) or serum is described. The document covers the principle of the method, the materials and equipment needed and essential aspects of the procedure. The subs

  20. Ghrelin receptor in energy homeostasis and obesity pathogenesis.

    Science.gov (United States)

    Li, Ziru; Li, Yin; Zhang, Weizhen

    2013-01-01

    The ghrelin receptor, also known as growth hormone secretagogue receptor (GHS-R), was identified in porcine and rat anterior pituitary membranes, where the synthetic secretagogue MK-0677 causes amplified pulsatile growth hormone (GH) release. In addition to its function in the stimulation of GH secretion, ghrelin, the natural ligand of ghrelin receptor is now recognized as a peptide hormone with fundamental influence on energy homeostasis. Despite the potential existence of multiple subtypes of ghrelin receptor, the effects of ghrelin on energy metabolism, obesity, and diabetes are mediated by its classical receptor GHS-R1a, whose activation requires the n-octanoylation of ghrelin. Here we review the current understanding of the role of the ghrelin receptor in the regulation of energy homeostasis. An overview of the ghrelin receptor is presented first, followed by the discussion on its effects on food intake, glucose homeostasis, and lipid metabolism. Finally, potential strategies for treating obesity and diabetes via manipulation of the ghrelin/ghrelin receptor axis are explored. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Plasma nitrite levels, total antioxidant status, total oxidant status, and oxidative stress index in patients with tension-type headache and fibromyalgia.

    Science.gov (United States)

    Neyal, Munife; Yimenicioglu, Fatih; Aydeniz, Ali; Taskin, Abdullah; Saglam, Sadullah; Cekmen, Mustafa; Neyal, Abdurrahman; Gursoy, Savas; Erel, Ozcan; Balat, Ayse

    2013-06-01

    Tension-type headache (TTH) and fibromyalgia syndrome (FM) are worldwide seen chronic pain syndromes of unknown etiology. Despite the growing body of data on pathophysiology and generation mechanisms of pain; our knowledge on pain mechanisms in both FM and TTH is yet to be limited. We investigated the plasma nitrite levels, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) in 35 TTH, 33 FM patients and 31 healthy controls. The mean plasma nitrite levels and TAS levels were significantly low and OSI was found to be significantly high in TTH and FM groups compared to the control group (p=0.001, p=0.001, p=0.001 and p=0.001, respectively). The mean serum TOS levels were also significantly higher in FM group according to the control group (p=0.034), but there was not a significant difference between TTH and control groups (p=0.066). These results indicated that; FM and TTH patients revealed higher oxidative stress index and lower total nitrite levels than healthy controls. We conclude that oxidative stress may have a role in the pathophysiological mechanisms of TTH and FM, although, whether it is the cause or the consequence, is not clear. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Altered Lipid and Salt Taste Responsivity in Ghrelin and GOAT Null Mice

    OpenAIRE

    Huan Cai; Wei-Na Cong; Caitlin M Daimon; Rui Wang; Tschöp, Matthias H.; Jean Sévigny; Bronwen Martin; Stuart Maudsley

    2013-01-01

    Taste perception plays an important role in regulating food preference, eating behavior and energy homeostasis. Taste perception is modulated by a variety of factors, including gastric hormones such as ghrelin. Ghrelin can regulate growth hormone release, food intake, adiposity, and energy metabolism. Octanoylation of ghrelin by ghrelin O-acyltransferase (GOAT) is a specific post-translational modification which is essential for many biological activities of ghrelin. Ghrelin and GOAT are both...

  3. Cisplatin-induced anorexia and ghrelin.

    Science.gov (United States)

    Hattori, Tomohisa; Yakabi, Koji; Takeda, Hiroshi

    2013-01-01

    Cisplatin, a formidable anticancer treatment, is used for several varieties of cancer. There are, however, many cases in which treatment must be abandoned due to a decrease in the patient's quality of life from loss of appetite associated with vomiting and nausea. There is a moderate degree of improvement in prevention of cisplatin-induced nausea and vomiting when serotonin (5-HT) 3 receptor antagonists, neurokinin 1 receptor antagonists, and steroids-either alone or in combination-are administered. The mechanism of action for anorexia, which continues during or after treatment, is, however, still unclear. This anorexia is, similar to the onset of vomiting and nausea, caused by the action of large amounts of 5-HT released as a result of cisplatin administration on tissue 5-HT receptors. Among the 5-HT receptors, the activation of 5-HT2b and 5-HT2c receptors, in particular, seems to play a major role in cisplatin-induced anorexia. Following activation of these two receptors, there is reduced gastric and hypothalamic secretion of the appetite-stimulating hormone ghrelin. There is ample evidence of the usefulness of exogenous ghrelin, synthetic ghrelin agonists, and the endogenous ghrelin signal-enhancer rikkunshito, which are expected to play significant roles in the clinical treatment and prevention of anorexia in future.

  4. Total plasma homocysteine is associated with hypertension in Type I diabetic patients

    DEFF Research Database (Denmark)

    Neugebauer, S; Tarnow, L; Stehouwer, C D

    2002-01-01

    between plasma homocysteine concentrations, methylenetetrahydrofolate reductase gene polymorphism, hypertension, diabetic microvascular and macrovascular complications associated with kidney function. METHODS: Vascular complications, hypertension, methylenetetrahydrofolate reductase genotype (RFLP....../l in patients with normal GFR are not related to vascular complications, but to hypertension (8.6-11.3 micro mol/l: OR 1.9; >11.3 micro mol/l: OR 3.7). The risk for coronary heart disease (CHD) was also enhanced by a plasma homocysteine concentration greater than 11.3 micro mol/l (OR 5.9). Although the T allele...... was an independent determinant of plasma homocysteine, the methylenetetrahydrofolate reductase gene polymorphism was neither associated with diabetic vascular complications nor with hypertension. CONCLUSION/INTERPRETATION: Increased plasma homocysteine concentrations but not the T allele per se, enhance the risk...

  5. Multi-species sequence comparison reveals conservation of ghrelin gene-derived splice variants encoding a truncated ghrelin peptide.

    Science.gov (United States)

    Seim, Inge; Jeffery, Penny L; Thomas, Patrick B; Walpole, Carina M; Maugham, Michelle; Fung, Jenny N T; Yap, Pei-Yi; O'Keeffe, Angela J; Lai, John; Whiteside, Eliza J; Herington, Adrian C; Chopin, Lisa K

    2016-06-01

    The peptide hormone ghrelin is a potent orexigen produced predominantly in the stomach. It has a number of other biological actions, including roles in appetite stimulation, energy balance, the stimulation of growth hormone release and the regulation of cell proliferation. Recently, several ghrelin gene splice variants have been described. Here, we attempted to identify conserved alternative splicing of the ghrelin gene by cross-species sequence comparisons. We identified a novel human exon 2-deleted variant and provide preliminary evidence that this splice variant and in1-ghrelin encode a C-terminally truncated form of the ghrelin peptide, termed minighrelin. These variants are expressed in humans and mice, demonstrating conservation of alternative splicing spanning 90 million years. Minighrelin appears to have similar actions to full-length ghrelin, as treatment with exogenous minighrelin peptide stimulates appetite and feeding in mice. Forced expression of the exon 2-deleted preproghrelin variant mirrors the effect of the canonical preproghrelin, stimulating cell proliferation and migration in the PC3 prostate cancer cell line. This is the first study to characterise an exon 2-deleted preproghrelin variant and to demonstrate sequence conservation of ghrelin gene-derived splice variants that encode a truncated ghrelin peptide. This adds further impetus for studies into the alternative splicing of the ghrelin gene and the function of novel ghrelin peptides in vertebrates.

  6. Pediatric reference intervals for plasma free and total metanephrines established with a parametric approach: relevance to the diagnosis of neuroblastoma.

    Science.gov (United States)

    Franscini, Laura Crosazzo; Vazquez-Montes, Maria; Buclin, Thierry; Perera, Rafael; Dunand, Marielle; Grouzmann, Eric; Beck-Popovic, Maja

    2015-04-01

    Urine catecholamines, vanillylmandelic, and homovanillic acid are recognized biomarkers for the diagnosis and follow-up of neuroblastoma. Plasma free (f) and total (t) normetanephrine (NMN), metanephrine (MN) and methoxytyramine (MT) could represent a convenient alternative to those urine markers. The primary objective of this study was to establish pediatric centile charts for plasma metanephrines. Secondarily, we explored their diagnostic performance in 10 patients with neuroblastoma. We recruited 191 children (69 females) free of neuroendocrine disease to establish reference intervals for plasma metanephrines, reported as centile curves for a given age and sex based on a parametric method using fractional polynomials models. Urine markers and plasma metanephrines were measured in 10 children with neuroblastoma at diagnosis. Plasma total metanephrines were measured by HPLC with coulometric detection and plasma free metanephrines by tandem LC-MS. We observed a significant age-dependence for tNMN, fNMN, and fMN, and a gender and age-dependence for tMN, fNMN, and fMN. Free MT was below the lower limit of quantification in 94% of the children. All patients with neuroblastoma at diagnosis were above the 97.5th percentile for tMT, tNMN, fNMN, and fMT, whereas their fMN and tMN were mostly within the normal range. As expected, urine assays were inconstantly predictive of the disease. A continuous model incorporating all data for a given analyte represents an appealing alternative to arbitrary partitioning of reference intervals across age categories. Plasma metanephrines are promising biomarkers for neuroblastoma, and their performances need to be confirmed in a prospective study on a large cohort of patients. © 2015 Wiley Periodicals, Inc.

  7. Acute phase response of selenium status and glutathione peroxidase activity in blood plasma before and after total knee arthroplasty surgery.

    Science.gov (United States)

    Defi, Irma Ruslina; Yamazaki, Chiho; Kameo, Satomi; Kobayashi, Kenji; Nakazawa, Minato; Shinya, Yanagisawa; Sato, Naoki; Wada, Naoki; Shirakura, Kenji; Koyama, Hiroshi

    2011-12-01

    Several studies show the consistent results of the decrease in plasma or serum selenium (Se) after surgery, and the change is suggested to be a negative acute phase response of Se to the surgical inflammation. Plasma glutathione peroxidase (GPx), which is included in the acute phase response proteins, is a selenoenzyme. However, previous studies failed to show any changes in GPx activity before and after surgery. In the present study, we investigated the Se- and selenoenzyme responses that accompany the acute inflammatory reactions during and following major surgery. Patients who underwent elective total knee arthroplasty surgery due to knee osteoarthritis at the Department of Orthopaedic Surgery at Gunma University Hospital in Japan were studied. The plasma Se concentration was determined, and the activity of plasma GPx was measured. C-reactive protein (CRP), albumin, blood urea nitrogen (BUN), and white blood cell (WBC) count were also analysed. Increases in the inflammatory biomarkers of CRP and WBC showed inflammatory reactions with the surgery. A significant increase in plasma GPx activity (p production of other series of acute phase proteins, the present results suggest that there is a redistribution of plasma Se to GPx that occurs as an acute phase response, and the source of Se for GPx could be, at least partly, from albumin.

  8. 老年人血浆ghrelin和瘦素水平改变与老年性厌食的关联%Relationship of changes of plasma ghrelin and leptin levels in old people and anorexia aging

    Institute of Scientific and Technical Information of China (English)

    齐健; 邱闻勇

    2007-01-01

    目的 研究老年人与摄食相关的激素ghrelin、瘦素、胰岛素的变化和相互关系,以及它们对老年人的食欲和摄食的影响.方法 用放射免疫法测定健康年轻人(18~25岁)和老年人(60~78岁)血浆ghrelin、瘦素和胰岛素浓度.结果 老年组血浆ghrelin浓度低于年轻组(P=0.027),与BMI负相关(r=-0.772,P<0.01).老年组血浆瘦素浓度高于年轻组(P<0.001),与BMI正相关(r=0.703,P<0.01).血浆ghrelin与瘦素负相关(r=-0.636,P<0.01).老年组血浆胰岛素浓度与年轻组差异无显著性(P=0.186),血浆胰岛素浓度与BMI、血浆ghrelin及瘦素浓度均无明显相关.结论 老年人循环中食欲减退的信号(瘦素)增强,而促进食欲的信号(ghrelin)减弱,可能是对BMI随年龄增长而产生的适应性反应,由此引起的饱感延长、饥饿感受抑可能是老年性厌食的诱因.

  9. Standard test method for analysis of total and isotopic uranium and total thorium in soils by inductively coupled plasma-mass spectrometry

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2008-01-01

    1.1 This test method covers the measurement of total uranium (U) and thorium (Th) concentrations in soils, as well as the determination of the isotopic weight percentages of 234U, 235U, 236U, and 238U, thereby allowing for the calculation of individual isotopic uranium activity or total uranium activity. This inductively coupled plasma-mass spectroscopy (ICP-MS) method is intended as an alternative analysis to methods such as alpha spectroscopy or thermal ionization mass spectroscopy (TIMS). Also, while this test method covers only those isotopes listed above, the instrumental technique may be expanded to cover other long-lived radioisotopes since the preparation technique includes the preconcentration of the actinide series of elements. The resultant sample volume can be further reduced for introduction into the ICP-MS via an electrothermal vaporization (ETV) unit or other sample introduction device, even though the standard peristaltic pump introduction is applied for this test method. The sample preparatio...

  10. Effects of acute recombinant human TSH (rhTSH on serum ghrelin levels.

    Directory of Open Access Journals (Sweden)

    Cristina eCiuoli

    2011-12-01

    Full Text Available Recent findings showed the presence of a reciprocal relationship between thyroid hormones and ghrelin, although the exact mechanism is not known. Design: Our study is addressed to evaluate the effect of acute exogenous rhTSH administration on serum ghrelin levels in athyreotic patients on replacement l-thyroxine therapy. The study group included fifty patients (16 males and 34 females submitted to total thyroidectomy and 131-iodine remnant ablation for differentiated thyroid cancer on l-thyroxine therapy. Mean age was 47.5 ± 16.5 years and mean BMI was 25.6 ± 5.01 kg/m². rhTSH was administrated at the dosage of 0.9 mg i.m once daily for two consecutive days. Blood samples were taken between 08.00 and 09.00 after a overnight fasting for measurement of TSH, FT3, FT4 and ghrelin before the first administration of rhTSH and for measurement of TSH and ghrelin 24 h, 48 h, 72 h and 96 h after the first administration of rhTSH. Results: Mean ± SD values of basal TSH were 0.54 ± 0.77 µU/ml without significant difference between females and males. As expected, after rhTSH administration TSH concentrations increased at 24 h and 48 h with peak TSH values ranging from 20.20 to 313 µU/ml (mean ± SD 98.4±66.7µU/ml. Mean ± SD values of basal ghrelin were 1085 ± 373 pg/ml without significant difference between males and females. After rhTSH administration ghrelin concentrations decreased significantly (p<0.01 at 24 h (mean ± SD 934 ±314 pg/ml p<0.01 and returned to pre-treatment levels at 96 h. Conclusion: Our study demonstrates that acute exogenous TSH administration has a suppressive effect on ghrelin secretion independent from changes in thyroid status.

  11. Involvement of Astrocytes in Mediating the Central Effects of Ghrelin

    Directory of Open Access Journals (Sweden)

    Laura M. Frago

    2017-03-01

    Full Text Available Although astrocytes are the most abundant cells in the mammalian brain, much remains to be learned about their molecular and functional features. Astrocytes express receptors for numerous hormones and metabolic factors, including the appetite-promoting hormone ghrelin. The metabolic effects of ghrelin are largely opposite to those of leptin, as it stimulates food intake and decreases energy expenditure. Ghrelin is also involved in glucose-sensing and glucose homeostasis. The widespread expression of the ghrelin receptor in the central nervous system suggests that this hormone is not only involved in metabolism, but also in other essential functions in the brain. In fact, ghrelin has been shown to promote cell survival and neuroprotection, with some studies exploring the use of ghrelin as a therapeutic agent against metabolic and neurodegenerative diseases. In this review, we highlight the possible role of glial cells as mediators of ghrelin’s actions within the brain.

  12. Review of novel aspects of the regulation of ghrelin secretion.

    Science.gov (United States)

    Al Massadi, Omar; Lear, Pamela V; Muller, Timo D; Lopez, Miguel; Dieguez, Carlos; Tschop, Matthias H; Nogueiras, Ruben

    2014-01-01

    The role of ghrelin in regulating metabolism and energy balance has been a subject of intense focus ever since its discovery. Ghrelin regulates energy balance in the short term by induction of appetite and in the longer term by increasing body weight and adiposity. It is the only known peripheral orexigenic hormone and one of the most potent endogenous orexigenic factors discovered to date. However, whilst extensively studied, the mechanism of ghrelin secretion is not well understood. A better understanding of the pathways controlling ghrelin secretion could be useful in the development of new therapeutic approaches to appetite-related disorders. Here, we discuss current knowledge of the processes that control ghrelin secretion, focusing on neural, chemical and hormonal stimuli. In addition, we share our view on the potential of targeting ghrelin for the treatment of eating disorders such as obesity, anorexia nervosa and cachexia.

  13. Involvement of Astrocytes in Mediating the Central Effects of Ghrelin

    Science.gov (United States)

    Frago, Laura M.; Chowen, Julie A.

    2017-01-01

    Although astrocytes are the most abundant cells in the mammalian brain, much remains to be learned about their molecular and functional features. Astrocytes express receptors for numerous hormones and metabolic factors, including the appetite-promoting hormone ghrelin. The metabolic effects of ghrelin are largely opposite to those of leptin, as it stimulates food intake and decreases energy expenditure. Ghrelin is also involved in glucose-sensing and glucose homeostasis. The widespread expression of the ghrelin receptor in the central nervous system suggests that this hormone is not only involved in metabolism, but also in other essential functions in the brain. In fact, ghrelin has been shown to promote cell survival and neuroprotection, with some studies exploring the use of ghrelin as a therapeutic agent against metabolic and neurodegenerative diseases. In this review, we highlight the possible role of glial cells as mediators of ghrelin’s actions within the brain. PMID:28257088

  14. Relationship between ghrelin, Helicobacter pylori and gastric mucosal atrophy in hemodialysis patients.

    Science.gov (United States)

    Ichikawa, Hitomi; Sugimoto, Mitsushige; Sakao, Yukitoshi; Sahara, Shu; Ohashi, Naro; Kato, Akihiko; Sugimoto, Ken; Furuta, Takahisa; Andoh, Akira; Sakao, Tadashi; Yasuda, Hideo

    2016-12-21

    To investigate the relationship between plasma ghrelin level, Helicobacter pylori (H. pylori) infection status and the severity of atrophy in hemodialysis patients. One hundred eights patients who received hemodialysis and 13 non-hemodialysis H. pylori-negative controls underwent gastroduodenoscopy to evaluate the severity of gastric atrophy. Serum levels of pepsinogen (PG) were measured as serum markers of gastric atrophy. H. pylori infection was evaluated by anti-H. pylori IgG antibody, rapid urease test and culture test. We classified H. pylori infection status as non-infection, present infection and past infection. In addition, plasma acyl-ghrelin and desacyl-ghrelin levels were measured by enzyme-linked immunosorbent assay. Infection rate of H. pylori was 45.4% (49/108). Acyl-ghrelin level in the non-infection group (39.4 ± 23.0 fmol/mL) was significantly higher than in the past (23.4 ± 19.9 fmol/mL, P = 0.005) and present infection groups (19.5 ± 14.0 fmol/mL, P atrophy (both P atrophy (24.5 ± 23.1 fmol/mL, 20.2 ± 14.9 fmol/mL and 18.3 ± 11.8 fmol/mL) than in those with non-atrophy (39.4 ± 22.2 fmol/mL, P = 0.039, P = 0.002 and P atrophy related to H. pylori infection.

  15. Effects of fruit and vegetable consumption on total antioxidant capacity of fasting and postprandial plasma samples

    DEFF Research Database (Denmark)

    Ravn-Haren, Gitte; Dragsted, L. O.; Pedersen, A.

    2001-01-01

    Fruits and vegetables are known to protect against cancer and heart disease. This is often ascribed to their high content of antioxidants. We have therefore tested whether a daily intake of fruits and vegetables corresponding to the recommended 600 g had any effect on the antioxidant activity of ...... of fasting and postprandial plasma samples. Antioxidant activity was determined by the Trolox Equivalent Antioxidant Capacity (TEAC) assay and the Ferric Reducing Ability of Plasma (FRAP) assay, which have been reported to be affected by the presence of dietary antioxidants....

  16. Effect of ghrelin on autonomic activity in healthy volunteers.

    Science.gov (United States)

    Soeki, Takeshi; Koshiba, Kunihiko; Niki, Toshiyuki; Kusunose, Kenya; Yamaguchi, Koji; Yamada, Hirotsugu; Wakatsuki, Tetsuzo; Shimabukuro, Michio; Minakuchi, Kazuo; Kishimoto, Ichiro; Kangawa, Kenji; Sata, Masataka

    2014-12-01

    Ghrelin is a novel growth hormone (GH)-releasing peptide originally isolated from the stomach. Recently, we have shown that ghrelin suppresses cardiac sympathetic activity and prevents early left ventricular remodeling in rats with myocardial infarction. In the present study, we evaluated the effect of ghrelin on autonomic nerve activity in healthy human subjects. An intravenous bolus of human synthetic ghrelin (10μg/kg) was administered to 10 healthy men (mean age, 33 years). Holter monitoring assessment was performed before and during 2h after the ghrelin therapy. The standard deviation of normal RR intervals (SDNN), square root of the mean of the sum of the squares of differences between adjacent RR intervals (rMSSD), high-frequency power (HF), and low-frequency power (LF) were analyzed. Blood samples were also obtained before and after the therapy. A single administration of ghrelin decreased both heart rate and blood pressure. Interestingly, ghrelin significantly decreased the LF and LF/HF ratio of heart rate variability and increased the SDNN, rMSSD, and HF. Ghrelin also elicited a marked increase in circulating GH, but not insulin-like growth factor-1. These data suggest that ghrelin might suppress cardiac sympathetic nerve activity and stimulate cardiac parasympathetic nerve activity. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Ghrelin in the fetal pancreas - a digital quantitation study

    DEFF Research Database (Denmark)

    Hasselby, Jane Preuss; Maroun, Lisa Leth; Federspiel, Birgitte Hartnack

    2012-01-01

    Hasselby JP, Maroun LL, Federspiel BH, Vainer B. Ghrelin in the fetal pancreas - a digital quantitation study. APMIS 2011. Ghrelin is a hormone produced by specialized neuroendocrine cells located in the fetal pancreas. In the adult, ghrelin has multiple effects, but in the fetus the role....... Immunohistochemical staining was performed, and the expression was quantitated using an automated digital image analysis system. The results showed ghrelin-producing cells as scattered single cells in ductular structures and acini throughout the gestation. From midgestation they were also found in the periphery...

  18. Nitrite-induced methemoglobinaemia affects blood ionized and total magnesium level by hydrolysis of plasma adenosine triphosphate in rat.

    Science.gov (United States)

    Rahman, Md Mizanur; Kim, Shang-Jin; Kim, Gi-Beum; Hong, Chul-Un; Lee, Young-Up; Kim, Sung-Zoo; Kim, Jin-Shang; Kang, Hyung-Sub

    2009-11-01

    The objective of this study was to evaluate the effects of sodium nitrite (NaNO(2))-induced methemoglobinaemia on plasma ATP (adenosine triphosphate) and corresponding changes of blood-ionized magnesium (iMg(2+)) as well as total magnesium (tMg(2+)) in a time-dependent manner. This study was performed on male Sprague-Dawley rats to which NaNO(2) was injected (10 mg/kg i.p.) to induce methemoglobinaemia. Methemoglobin (MetHb) in blood was measured before (0 min.) and after 10, 30, 60 and 120 min. of NaNO(2) injection. At respective time points, the tMg(2+), blood ions and gases were measured by atomic absorption spectrometry and ion selective electrode, respectively. Haematological parameters were checked by automatic blood cell count, and blood films were observed under light microscope. Plasma ATP was measured by bioluminescence assay using a luminometer, and plasma proteins were measured by an automatic analyser. Blood cell count (RBC, WBC and platelet), haematocrit, and haemoglobin were found to be decreased with the advancement of MetHb concentration. With the gradual increase of MetHb concentration, the plasma ATP decreased and blood iMg(2+) and plasma tMg(2+) increased significantly as time passed by in comparison with the pre-drug values. A significant decrease of the ratio of ionized calcium to iMg(2+), Na(+) and increase of K(+) was observed. In conclusion, NaNO(2)-induced methemoglobinaemia is a cause of hydrolysis of plasma ATP which is responsible for the increase of blood iMg(2+) and plasma tMg(2+) in rats.

  19. The effect of an induced copper deficiency on the total plasma ...

    African Journals Online (AJOL)

    decline in the plasma copper concentration from 160 fLg/dlto 56 fLg/dlwas achieved. Further indications ... that the need for copper is higher for reproduction than for normal body maintenance. Die effek van 'n ..... Trace elements in Human and.

  20. Changes in total plasma and serum N-glycome composition and patient-controlled analgesia after major abdominal surgery.

    Science.gov (United States)

    Gudelj, Ivan; Baciarello, Marco; Ugrina, Ivo; De Gregori, Manuela; Napolioni, Valerio; Ingelmo, Pablo M; Bugada, Dario; De Gregori, Simona; Đerek, Lovorka; Pučić-Baković, Maja; Novokmet, Mislav; Gornik, Olga; Saccani Jotti, Gloria; Meschi, Tiziana; Lauc, Gordan; Allegri, Massimo

    2016-08-09

    Systemic inflammation participates to the complex healing process occurring after major surgery, thus directly affecting the surgical outcome and patient recovery. Total plasma N-glycome might be an indicator of inflammation after major surgery, as well as an anti-inflammatory therapy response marker, since protein glycosylation plays an essential role in the inflammatory cascade. Therefore, we assessed the effects of surgery on the total plasma N-glycome and the association with self-administration of postoperative morphine in two cohorts of patients that underwent major abdominal surgery. We found that plasma N-glycome undergoes significant changes one day after surgery and intensifies one day later, thus indicating a systemic physiological response. In particular, we observed the increase of bisialylated biantennary glycan, A2G2S[3,6]2, 12 hours after surgery, which progressively increased until 48 postoperative hours. Most changes occurred 24 hours after surgery with the decrease of most core-fucosylated biantennary structures, as well as the increase in sialylated tetraantennary and FA3G3S[3,3,3]3 structures. Moreover, we observed a progressive increase of sialylated triantennary and tetraantennary structures two days after surgery, with a concomitant decrease of the structures containing bisecting N-acetylglucosamine along with bi- and trisialylated triantennary glycans. We did not find any statistically significant association between morphine consumption and plasma N-glycome.

  1. N- and O-linked glycosylation of total plasma glycoproteins in galactosemia.

    Science.gov (United States)

    Liu, Ying; Xia, Baoyun; Gleason, Tyler J; Castañeda, Uriel; He, Miao; Berry, Gerard T; Fridovich-Keil, Judith L

    2012-08-01

    Classic galactosemia is a potentially lethal metabolic disorder that results from profound impairment of the enzyme galactose-1-phosphate uridylyltransferase (GALT); despite decades of research, the underlying mechanism of pathophysiology remains unclear. Previous studies of plasma and tissue samples from patients with classic galactosemia have revealed defects of protein and lipid glycosylation, however, the underlying bases for these defects and their clinical significance, if any, has remained unclear. As a step toward addressing these questions we characterized both the N- and O-linked glycomes of plasma proteins from neonates, infants, children, and adults with galactosemia using mass spectrometry and asked (1) whether similar or disparate defects exist for N-linked and O-linked modifications, (2) what factors correlate with the severity of these defects in different patients, and perhaps most important, (3) whether there is any apparent relationship between chronic glycosylation defects and long-term outcome in patients. We found that some but not all of the galactosemic neonates tested exhibited abnormal N- and O-linked glycosylation of plasma proteins. The types of abnormalities seen were similar between N- and O-linked moieties, but the extent of the defects varied between patients. Age, gender, GALT genotype, and predicted residual GALT activity all failed to explain the extent of the glycosylation defect in the samples studied. Dietary galactose restriction markedly normalized both the N- and O-linked glycosylation patterns for all infants tested; however, any remaining glycosylation defects evident in the plasma of older children or adults on galactose-restricted diets showed no correlation with clinical outcome. These data cannot rule out the possibility that subtle or localized glycosylation defects, not detectable by our methods or not reflected in plasma, may contribute to acute or long-term outcome severity.

  2. Taking Two to Tango: A Role for Ghrelin Receptor Heterodimerization in Stress and Reward

    Directory of Open Access Journals (Sweden)

    Harriet eSchellekens

    2013-08-01

    Full Text Available The gut hormone, ghrelin, is the only known peripherally derived orexigenic signal. It activates its centrally expressed receptor, the growth hormone secretagogue receptor (GHS-R1a, to stimulate food intake. The ghrelin signalling system has recently been suggested to play a key role at the interface of homeostatic control of appetite and the hedonic aspects of food intake, as a critical role for ghrelin in dopaminergic mesolimbic circuits involved in reward signalling has emerged. Moreover, enhanced plasma ghrelin levels are associated with conditions of physiological stress, which may underline the drive to eat calorie-dense ‘comfort-foods’ and signifies a role for ghrelin in stress-induced food reward behaviours. These complex and diverse functionalities of the ghrelinergic system are not yet fully elucidated and likely involve crosstalk with additional signalling systems. Interestingly, accumulating data over the last few years has shown the GHS-R1a receptor to dimerize with several additional G-protein coupled receptors (GPCRs involved in appetite signalling and reward, including the GHS-R1b receptor, the melanocortin 3 receptor (MC3, dopamine receptors (D1 and D2, and more recently, the serotonin 2C receptor (5-HT2C. GHS-R1a dimerization was shown to affect downstream signalling and receptor trafficking suggesting a potential novel mechanism for fine-tuning GHS-R1a receptor mediated activity. This review summarizes ghrelin’s role in food reward and stress and outlines the GHS-R1a dimer pairs identified to date. In addition, the downstream signalling and potential functional consequences of dimerization of the GHS-R1a receptor in appetite and stress-induced food reward behaviour are discussed. The existence of multiple GHS-R1a heterodimers has important consequences for future pharmacotherapies as it significantly increases the pharmacological diversity of the GHS-R1a receptor and has the potential to enhance specificity of novel

  3. Effect of oral glucose administration on rebound growth hormone release in normal and obese women: the role of adiposity, insulin sensitivity and ghrelin.

    Directory of Open Access Journals (Sweden)

    Lara Pena-Bello

    Full Text Available Metabolic substrates and nutritional status play a major role in growth hormone (GH secretion. Uncovering the mechanisms involved in GH secretion following oral glucose (OG administration in normal and obese patients is a pending issue.The aim of this study was to investigate GH after OG in relation with adiposity, insulin secretion and action, and ghrelin secretion in obese and healthy women, to further elucidate the mechanism of GH secretion after OG and the altered GH secretion in obesity.We included 64 healthy and obese women. After an overnight fast, 75 g of OG were administered; GH, glucose, insulin and ghrelin were obtained during 300 minutes. Insulin secretion and action indices and the area under the curve (AUC were calculated for GH, glucose, insulin and ghrelin. Univariate and multivariate linear regression analyses were employed.The AUC of GH (μg/L•min was lower in obese (249.8±41.8 than in healthy women (490.4±74.6, P=0.001. The AUC of total ghrelin (pg/mL•min was lower in obese (240995.5±11094.2 than in healthy women (340797.5±37757.5, P=0.042. There were significant correlations between GH secretion and the different adiposity, insulin secretion and action, and ghrelin secretion indices. After multivariate analysis only ghrelin AUC remained a significant predictor for fasting and peak GH.

  4. Ghrelin in Diabetes and Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Leena Pulkkinen

    2010-01-01

    Full Text Available Metabolic syndrome is a cluster of related risk factors for cardiovascular disease, type 2 diabetes and liver disease. Obesity, which has become a global public health problem, is one of the major risk factors for development of metabolic syndrome and type 2 diabetes. Obesity is a complex disease, caused by the interplay between environmental and genetic factors. Ghrelin is one of the circulating peptides, which stimulates appetite and regulates energy balance, and thus is one of the candidate genes for obesity and T2DM. During the last years both basic research and genetic association studies have revealed association between the ghrelin gene and obesity, metabolic syndrome or type 2 diabetes

  5. Ghrelin improves burn-induced delayed gastrointestinal transit in rats.

    Science.gov (United States)

    Sallam, H S; Oliveira, H M; Gan, H T; Herndon, D N; Chen, J D Z

    2007-01-01

    Delayed gastrointestinal transit is common in patients with severe burn. Ghrelin is a potent prokinetic peptide. We aimed at testing the effect of ghrelin on burn-induced delayed gastrointestinal transit in rats. Gastric emptying (GE), intestinal transit (IT), and colonic transit (CT) studies were performed in male Sprague-Dawley rats. Rats were randomized into two main groups as follows: sham injury and ghrelin-treated burn injury with doses of 0, 2, 5, and 10 nmol/rat ip 6 h after burn. Sham/burn injury was induced under anesthesia. Rats received a phenol red meal 20 min following ghrelin injection. Based on the most effective ghrelin dose, 1 mg/kg sc atropine was given 30 min before the ghrelin in one group of rats for each study. The rats in each group were killed 30-90 min later; their stomachs, intestines, and colons were harvested immediately, and the amount of phenol red recovered was measured. Percentage of gastric emptying (GE%) and geometric center for IT and CT were calculated. We found 1) severe cutaneous burn injury significantly delayed GE, IT, and CT compared with sham injury (P CT; 3) the most effective dose of ghrelin was 2 nmol/rat; and 4) atropine blocked the prokinetic effects of ghrelin on GE% and IT. In conclusion, ghrelin normalizes burn-induced delayed GE and IT but has no effect on CT in rats. The prokinetic effects of ghrelin are exerted via the cholinergic pathway. Ghrelin may have a therapeutic potential for burn patients with delayed upper gastrointestinal transit.

  6. Ghrelin receptor gene polymorphisms are associated with female metabolic syndrome in Chinese population

    Institute of Scientific and Technical Information of China (English)

    LI Wei-ju; ZHEN Yi-song; SUN Kai; XUE Hao; SONG Xiao-dong; WANG Yi-bo; FAN Xiao-han; HAN Yun-feng; HUI Ru-tai

    2008-01-01

    Background The ghrelin plays an important role in the regulation of food intake and energy homeostasis.Therefore,the ghrelin receptor gene (GHSR) is an excellent candidate for studying metabolic syndrome.This study aimed to investigate whether polymorphisms in ghrelin receptor gene are associated with metabolic syndrome in Chinese population.Methods Subjects consisted of 698 patients aged 41 to 80 years,diagnosed as metabolic syndrome by International Diabetes Federation (IDF) 2005 criteria,and 762 age-and gender-matched controls.Three variants within the GHSR were selected and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).Odds ratios were estimated using a case-control study design by controlling confounding factors.Results The NA genotype (rs2922126) in the promoter was associated with metabolic syndrome (OR 1.41,95%CI 1.03-1.94),increased waist circumference (OR 1.75,95%CI 1.26-2.42),and increased fast blood glucose (OR 1.49,95%CI 1.07-2.06) in women.The A/A genotype (rs509030) in the intron was associated with lower plasma high density lipoprotein in women (OR 1.37,95%CI 1.02-1.84).Conclusion The polymorphisms within GHSR might be a genetic risk factor for metabolic syndrome in women.

  7. Plasma total homocysteine (THCY) level and other biochemical risk factors in hypertensives with and without cardiovascular events

    Institute of Scientific and Technical Information of China (English)

    Akande AA; Salisu OT; Omotoso ABO; Kolo PM

    2009-01-01

    Objective:The aim of this study is to assess the correlation between traditional cardiovascular risk factors and elevated plasma tHcy level in Nigerian hypertensive. Methods: Thirty-six hypertensive patients were recruited with 36 age and sex-matched controls. The age, sex and anthropometric measurements including height, weight and body mass index (BMI) were taken. Plasma total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), tri-glycerides and tHey were analyzed. The results of the two groups were compared. Results: The mean total cholesterol and LDL-C were significantly higher in the subjects than in the controls (P=0.01 and 0.03 respectively). On the other hand, means of HDL-C and triglycerides were not significantly different between the two groups (P = 0.06 and O. 68 respectively). Mean total plasma tHey was (12. 95±4.9)μmol/L in hypertensive patients when compared with (11.29±3.6)μmol/L in the controls (P =0.09), however the mean they was significantly higher in hypertensive patients who had stroke or myocardial infarction than those without these complications (one way Anova F = 3.63, P =0.04). Significant positive correlation was seen between tHcy and systolic blood pressure, diastolic blood pressure, BMI and LDL-C. Conclusion:The study suggests that elevated plasma tH-ey may predict occurrence of cardiovascular complications in hypertensive individuals.

  8. Integrating GHS into the Ghrelin System

    Directory of Open Access Journals (Sweden)

    Johannes D. Veldhuis

    2010-01-01

    Full Text Available Oligopeptide derivatives of metenkephalin were found to stimulate growth-hormone (GH release directly by pituitary somatotrope cells in vitro in 1977. Members of this class of peptides and nonpeptidyl mimetics are referred to as GH secretagogues (GHSs. A specific guanosine triphosphatate-binding protein-associated heptahelical transmembrane receptor for GHS was cloned in 1996. An endogenous ligand for the GHS receptor, acylghrelin, was identified in 1999. Expression of ghrelin and homonymous receptor occurs in the brain, pituitary gland, stomach, endothelium/vascular smooth muscle, pancreas, placenta, intestine, heart, bone, and other tissues. Principal actions of this peptidergic system include stimulation of GH release via combined hypothalamopituitary mechanisms, orexigenesis (appetitive enhancement, insulinostasis (inhibition of insulin secretion, cardiovascular effects (decreased mean arterial pressure and vasodilation, stimulation of gastric motility and acid secretion, adipogenesis with repression of fat oxidation, and antiapoptosis (antagonism of endothelial, neuronal, and cardiomyocyte death. The array of known and proposed interactions of ghrelin with key metabolic signals makes ghrelin and its receptor prime targets for drug development.

  9. Ghrelin response to carbohydrate-enriched breakfast is related to insulin

    NARCIS (Netherlands)

    Blom, W.A.M.; Stafleu, A.; Graaf, de C.; Kok, F.J.; Schaafsma, G.; Hendriks, H.F.J.

    2005-01-01

    Ghrelin plays an important role in the regulation of food intake. Little is known about how ghrelin concentrations are modified by dietary factors. Objective: We examined the effects of both amount and type of carbohydrate on ghrelin concentrations and all correlations among the variables ghrelin, g

  10. Early weight regain after gastric bypass does not affect insulin sensitivity but is associated with higher ghrelin levels

    Science.gov (United States)

    Tamboli, Robyn A.; Breitman, Igal; Marks-Shulman, Pam A.; Jabbour, Kareem; Melvin, Willie; Williams, Brandon; Clements, Ronald H.; Feurer, Irene D.; Abumrad, Naji N.

    2014-01-01

    Objectives We sought to determine: 1) if early weight regain between one and two years after RYGB is associated with worsened hepatic and peripheral insulin sensitivity, and 2) if preoperative levels of ghrelin and leptin are associated with early weight regain after RYGB. Design and Methods Hepatic and peripheral insulin sensitivity and ghrelin and leptin plasma levels were assessed longitudinally in 45 subjects before RYGB and at one month, six months, one year, and two years post operatively. Weight regain was defined as ≥ 5% increase in body weight between one and two years after RYGB. Results Weight regain occurred in 33% of subjects, with an average increase in body weight of 10 ± 5 % (8.5 ± 3.3 kg). Weight regain was not associated with worsening of peripheral or hepatic insulin sensitivity. Subjects with weight regain after RYGB had higher preoperative and postoperative levels of ghrelin compared to those who maintained or lost weight during this time. Conversely, the trajectories of leptin levels corresponded with the trajectories of fat mass in both groups. Conclusions Early weight regain after RYGB is not associated with a reversal of improvements in insulin sensitivity. Higher preoperative ghrelin levels might identify patients that are more susceptible to weight regain after RYGB. PMID:24777992

  11. Early weight regain after gastric bypass does not affect insulin sensitivity but is associated with elevated ghrelin.

    Science.gov (United States)

    Tamboli, Robyn A; Breitman, Igal; Marks-Shulman, Pam A; Jabbour, Kareem; Melvin, Willie; Williams, Brandon; Clements, Ronald H; Feurer, Irene D; Abumrad, Naji N

    2014-07-01

    We sought to determine: (1) if early weight regain between 1 and 2 years after Roux-en-Y gastric bypass (RYGB) is associated with worsened hepatic and peripheral insulin sensitivity, and (2) if preoperative levels of ghrelin and leptin are associated with early weight regain after RYGB. Hepatic and peripheral insulin sensitivity and ghrelin and leptin plasma levels were assessed longitudinally in 45 subjects before RYGB and at 1 month, 6 months, 1 year, and 2 years postoperatively. Weight regain was defined as ≥5% increase in body weight between 1 and 2 years after RYGB. Weight regain occurred in 33% of subjects, with an average increase in body weight of 10 ± 5% (8.5 ± 3.3 kg). Weight regain was not associated with worsening of peripheral or hepatic insulin sensitivity. Subjects with weight regain after RYGB had higher preoperative and postoperative levels of ghrelin compared to those who maintained or lost weight during this time. Conversely, the trajectories of leptin levels corresponded with the trajectories of fat mass in both groups. Early weight regain after RYGB is not associated with a reversal of improvements in insulin sensitivity. Higher preoperative ghrelin levels might identify patients that are more susceptible to weight regain after RYGB. Copyright © 2014 The Obesity Society.

  12. Speed associated with plasma pH, oxygen content, total protein and urea in an 80 km race.

    Science.gov (United States)

    Hoffman, R M; Hess, T M; Williams, C A; Kronfeld, D S; Griewe-Crandell, K M; Waldron, J E; Graham-Thiers, P M; Gay, L S; Splan, R K; Saker, K E; Harris, P A

    2002-09-01

    To test the hypothesis that endurance performance may be related quantitatively to changes in blood, we measured selected blood variables then determined their reference ranges and associations with speed during an 80 km race. The plan had 46 horses in a 2 x 2 factorial design testing a potassium-free electrolyte mix and a vitamin supplement. Blood samples were collected before the race, at 21, 37, 56 and 80 km, and 20 min after finishing, for assay of haematocrit, plasma pH, pO2, pCO2, [Na+], [K+], [Ca++], [Mg++], [Cl-], lactate, glucose, urea, cortisol, alpha-tocopherol, ascorbate, creatine kinase, aspartate amino transferase, lipid hydroperoxides, total protein, albumin and creatinine, and erythrocyte glutathione and glutathione peroxidase. Data from 34 finishers were analysed statistically. Reference ranges for resting and running horses were wide and overlapping and, therefore, limiting with respect to evaluation of individual horses. Speed correlations were most repeatable, with variables reflecting blood oxygen transport (enabling exercise), acidity and electrolytes (limiting exercise) and total protein (enabling then, perhaps, limiting). Stepwise regressions also included plasma urea concentration (limiting). The association of speed with less plasma acidity and urea suggests the potential for fat adaptation and protein restriction in endurance horses, as found previously in Arabians performing repeated sprints. Conditioning horses fed fat-fortified and protein-restricted diets may not only improve performance but also avoid grain-associated disorders.

  13. Relationship between plasma total homocysteine level and dietary caffeine and vitamin B6 intakes in pregnant women.

    Science.gov (United States)

    Shiraishi, Mie; Haruna, Megumi; Matsuzaki, Masayo; Ota, Erika; Murayama, Ryoko; Sasaki, Satoshi; Yeo, SeonAe; Murashima, Sachiyo

    2014-06-01

    A high total homocysteine (tHcy) level during pregnancy is a risk factor for adverse perinatal outcomes, such as fetal growth restriction and preeclampsia. Caffeine is assumed to increase tHcy levels by acting as a vitamin B6 antagonist. The objective of this study was to examine a relationship between circulating tHcy levels and dietary caffeine and vitamin B6 intakes in pregnant Japanese women. A total of 321 healthy women with singleton pregnancies were recruited in metropolitan Tokyo, from June to December 2008, resulting in the final number included in the study as 254. Dietary caffeine intakes did not correlate with plasma tHcy levels. When we analyzed the data according to caffeinated beverages, caffeinated tea consumption was positively associated with plasma tHcy levels only among the women with a high intake of vitamin B6 , after controlling for confounding factors (P = 0.029). No correlation between coffee consumption and plasma tHcy levels was found. Pregnant Japanese women might need to cut down the consumption of caffeinated tea as well as take sufficient vitamin B6 in order to prevent the tHcy levels from increasing.

  14. Ghrelin对败血症休克的影响%Effect of ghrelin on septic shock in rats

    Institute of Scientific and Technical Information of China (English)

    常林; 杜军保; 高连如; 庞永正; 唐朝枢

    2003-01-01

    目的:研究ghrelin对大鼠晚期败血症休克的防治作用.方法:用盲肠结扎并穿刺法制备大鼠败血症休克模型,在术后即刻和8小时分别从股静脉和皮下注射ghrelin 10 nmol/kg.术后18 h测定大鼠的血流动力学指标、血浆ghrelin、乳酸、葡萄糖浓度及心肌ATP含量.结果:与败血症休克组比较,ghrelin治疗组大鼠血压升高了33%,+LYdp/dtmax和-LVdp/dtmax值分别增加了27%和33%,而LVEDP降低了33%,血糖水平升高了54%,血浆乳酸浓度降低了40%,心肌ATP含量增加了22%(P<0.01).死亡率由44%降到25%.败血症休克大鼠血浆ghrelin水平比假手术组(149±23)pm0l/L增加了51%(P<0.01),血浆ghrelin水平与动脉血压和血糖值呈显著负相关(相关系数分别为-0.721和-0.811,P<0.01).结论:ghrelin治疗可以部分纠正败血症休克大鼠的血流动力学紊乱和代谢障碍.%AIM: To study the role of ghrelin in the late stage of septic shock in rats. METHODS: The rat model of septic shock was made by caecal ligation and perforation. At the time of operation ghrelin 10 nmol/kg was infused through femoral vein followed by a sc injection at 8 h after operation. Hemodynamic parameters including heart rate (HR), mean arterial blood pressure (MABP), LVdp/dtmax, and left ventricular end-diastolic pressure (LVEDP) in survival rats were measured at 18 h after surgery. Plasma glucose and lactate concentrations, plasma ghrelin level and myocardial ATP content were assayed. The mortality rate in rats with septic shock was also observed.RESULTS: Compared to that of septic shock group, MABP of rats in ghrelin-treated group increased by 33 % (P<0.01). The values of +LVdp/dtmax and -LVdp/dtmaxincreased by 27 % and 33 %, respectively (P<0.01), but LVEDP decreased by 33 % (P<0.01). The plasma glucose concentration and myocardial ATP content increased by 53 % and 22 %, respectively, but plasma lactate concentration decreased by 40 % in ghrelin-treated rats (P<0.01).The

  15. Effect of ghrelin on inflammatory response in lung contusion.

    Science.gov (United States)

    Guven, Berrak; Gokce, Mertol; Saydam, Ozkan; Can, Murat; Bektas, Sibel; Yurtlu, Serhan

    2013-02-01

    The purpose of this study was to investigate the effects of ghrelin on inflammatory response and tissue damage following trauma-induced acute lung injury. Thirty male wistar albino rats (300-400 g) were randomly assigned into three groups: control group (n = 6), lung contusion plus saline (saline-treated, n = 12), and lung contusion plus ghrelin (ghrelin-treated, n = 12). Saline- or ghrelin-treated traumatic rats were sacrificed at two time points (24 and 72 hours) after lung contusion. Blood was collected for the analysis of serum adenosine deaminase (ADA). Tissue transforming growth factor-beta 1 (TGF-β1) and matrix metalloproteinase-2 (MMP-2) levels were measured by enzyme-linked immunosorbent assay and histopathological examination was performed on the lung tissue samples. Our results indicated that ghrelin significantly reduced morphologic damages. Serum ADA activities were significantly decreased after lung contusion and this decline started early with ghrelin treatment. TGF-β1 and MMP-2 levels in lung tissue were elevated at 72 hours after lung contusion and treatment with ghrelin significantly increased TGF-β1 level and reduced MMP-2 level. In conclusion, our study demonstrates that acute lung injury initiated proinflammatory responses and ghrelin administration showed an anti-inflammatory effect in lung contusion.

  16. Ghrelin expression in dissociated cultures, of the rat neocortex

    NARCIS (Netherlands)

    Stoyanova, Irina I.; Wiertz, Remy W.F.; Rutten, Wim L.C.

    2009-01-01

    Ghrelin is a hormone, initially described as a gastric peptide stimulating appetite and growth hormone secretrion, which also has an important role in the regulation of many other processes including higher brain functions. Ghrelin has been described in situ in different part of the brain, but so fa

  17. The effects of ghrelin on colonic anastomosis healing in rats

    Directory of Open Access Journals (Sweden)

    Canan Ceran

    2013-01-01

    Full Text Available OBJECTIVES: In addition to its roles in the stimulation of growth hormone secretion and the regulation of appetite and metabolism, ghrelin exerts immunomodulatory, anti-inflammatory and antioxidant actions in several organ systems. In this study, we investigated the effects of ghrelin on the healing of experimental colonic anastomoses. METHODS: Wistar rats were randomly divided into two groups (n = 10 in each. A segment of colon was excised, and an end-to-end anastomosis was performed in the distal colon. The Ghrelin Group received 10 ng/kg/day IP ghrelin for seven days postoperatively, whereas the Control Group received an identical volume of saline. On the seventh postoperative day, the anastomotic bursting pressures and hydroxyproline levels were measured, and adhesion formation around the anastomoses was examined. Histopathological analyses were performed to evaluate inflammatory cell infiltration, fibroblast infiltration, collagen density and neovascularization. RESULTS: In the Ghrelin Group, the bursting pressure and hydroxyproline levels were significantly higher than in the Control Group. The adhesion formation scores were lower in the Ghrelin Group than in the Control Group. Although the inflammatory cell infiltration was diminished in the Ghrelin Group, the degrees of fibroblast infiltration, collagen density and neovascularization were not significantly different between the groups. CONCLUSION: Our results indicate that ghrelin improves the healing of colonic anastomoses in rats.

  18. Obesity, food intake and exercise: Relationship with ghrelin

    National Research Council Canada - National Science Library

    Gul Tiryaki-Sonmez; Serife Vatansever; Burcin Olcucu; Brad Schoenfeld

    2015-01-01

    ... – and long-term energy homeostasis. In the presence of increased obesity, decreased physical activity, and high food consumption, the relationship between exercise, appetite, food intake and ghrelin levels has important implications. In this review, we discuss the effect of acute and chronic exercise performance on appetite, food intake and ghrelin and their relationships.

  19. Ghrelin receptor regulates adipose tissue inflammation in aging

    Science.gov (United States)

    Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth ho...

  20. Protective and therapeutic effects of ghrelin in the gut.

    Science.gov (United States)

    Warzecha, Z; Dembinski, A

    2012-01-01

    Ghrelin, a peptide predominantly produced in the stomach exhibits numerous physiological functions, including stimulation of growth hormone release, food intake and gastric empting, and regulation of energy expenditure. This peptide exhibits also some protective and healing-promoting effects. This review summarizes the recent findings concerning animal and human data showing protective and therapeutic effects of ghrelin in the gut.

  1. The role of ghrelin in GH secretion and GH disorders.

    Science.gov (United States)

    Nass, Ralf; Gaylinn, Bruce D; Thorner, Michael O

    2011-06-20

    In humans, growth hormone (GH) is secreted from the anterior pituitary in a pulsatile pattern. The traditional view is that this secretory pattern is driven by two counter regulatory neurohormones, GHRH and somatostatin. Ghrelin, the natural ligand for the growth hormone (GH)-secretagogue receptor (GHS-R), is produced in the stomach. Ghrelin is the strongest GH secretagogue known to date, but the role of endogenous ghrelin in the regulation of circulating GH levels remains controversial. The following review examines the evidence suggesting that endogenous ghrelin may be a key regulator of GH peak amplitude and discusses studies of diseases with altered GH levels, where it is found that in these states GH and ghrelin levels change in a similar way.

  2. INFLUENCE OF CHRONIC EXERCISE ON RED CELL ANTIOXIDANT DEFENSE, PLASMA MALONDIALDEHYDE AND TOTAL ANTIOXIDANT CAPACITY IN HYPERCHOLESTEROLEMIC RABBITS

    Directory of Open Access Journals (Sweden)

    Mohsen Alipour

    2006-12-01

    Full Text Available Despite the knowledge on the antiatherogenic effects of exercise, the mechanism by which exercise reduces atherogenic risk remains unknown. In this study, we investigated the hypothesis that chronic exercise-induced oxidative stress may increase plasma total antioxidant capacity and antioxidant defense in the red cells. For 8 weeks, 60 male Dutch rabbits were fed rabbit chow with or without the addition of 2% cholesterol. The animals were further divided into rest and exercise groups (n = 15 for each group. Animals in exercise groups ran on a rodent treadmill at 15 m/min for 10 to 60 minutes gradually for 5 days per week for a total of 8 weeks. At the end of experiments, blood samples were collected and glutathione peroxidase (GPX, superoxide dismutase (SOD, and catalase (CAT activities were determined in red blood cells. Total antioxidant capacity (TAC, malondialdehyde (MDA and total thiol (T-SH levels were measured in plasma. Thoracic aorta and carotid arteries were isolated for histological examination to evaluate atherosclerosis. Eight weeks of chronic exercise reduced atherogenic diet-induced atherosclerotic lesions in all the arteries studied, along with positive changes in cholesterol profile, especially increase of serum HDL-C level. Plasma MDA, TAC and T-SH concentrations were enhanced by exercise in both control and hypercholesterolemic diet groups. Erythrocyte catalase activity was significantly increased by chronic exercise (p < 0.05, whereas total SOD activity rose with exercise only in the control group. Surprisingly, GPX activity was significantly reduced (P < 0.05 in response to exercise in the control group and also in the high cholesterol diet group. Exercise is a useful tool for the prevention and regression of atherosclerosis which is evident by our findings of the enhancement of plasma TAC and positive change in serum cholesterol profile. However, the effect of exercise on red cell antioxidant activities is limited in the

  3. Plasma total oxidant and antioxidant status after oral glucose tolerance and mixed meal tests in patients with polycystic ovary syndrome.

    Science.gov (United States)

    Kucukaydın, Zehra; Duran, Cevdet; Basaran, Mustafa; Camlica, Fatos; Erdem, Sami Said; Basaran, Ahmet; Kutlu, Orkide; Burnik, Ferda Sevimli; Elmas, Halis; Gonen, Mustafa Sait

    2016-10-01

    Insulin resistance (IR) and increased oxidative stress (OS) are the characteristics of polycystic ovary syndrome (PCOS). In this study, we aimed to evaluate the effects of oral glucose tolerance (OGTT) and mixed meal tests (MMT) on plasma total oxidant (TOS) and total antioxidant status (TAS) in patients with PCOS and the relationship between these parameters and IR, calculated via homeostasis of model assessment-IR (HOMA-IR) and Matsuda's insulin sensitivity index (ISI) derived from OGTT and MMT. Twenty-two patients with PCOS, and age- and body mass index (BMI)-matched 20 women as controls were enrolled into the study. Five-hour OGTT and MMT were performed on different days, and before and after these tests, plasma TOS and TAS levels were investigated. IR was calculated with HOMA-IR and Matsuda's ISI. HOMA-IR levels were higher in patients with PCOS, compared to controls, while Matsuda's ISI derived from OGTT and MMT was higher in controls. Plasma TOS levels before OGTT and MMT were higher in patients with PCOS than controls, while TAS levels were similar. After OGTT, plasma TOS levels became decreased at 5th hour, when compared to baseline values in PCOS group. Likewise, the same decrement was found in controls, but the decrement was not significant. After OGTT and MMT at 5th hour, no changes were observed in TAS levels, compared to baseline. Matsuda's ISIs derived from OGTT and MMT can be used instead of each other, and interestingly, we found a decrease in TOS levels after OGTT in patients with PCOS.

  4. Regulation of appetite in lean and obese adolescents after exercise: role of acylated and desacyl ghrelin.

    Science.gov (United States)

    Mackelvie, Kerry J; Meneilly, Graydon S; Elahi, Dariush; Wong, Alfred C K; Barr, Susan I; Chanoine, Jean-Pierre

    2007-02-01

    Increased physical activity is an integral part of weight loss programs in adolescents. We hypothesized that exercise could affect appetite-regulating hormones and the subjective desire to eat, which could partly explain the poor success rate of the existing interventions. The objective of this study was to investigate prospectively the effects of exercise on acylated ghrelin (AG) and desacyl ghrelin (DG) concentrations and on appetite. The setting for this study was a tertiary care center. Normal-weight [NW; body mass index (mean +/- se), 20.7 +/- 0.5 kg/m2] and overweight (OW; body mass index, 32.4 +/- 1.7) male adolescents (n = 17/group, age 15.3 +/- 0.2 yr) were studied. Those studied participated in 5 consecutive days of aerobic exercise (1 h/d). Changes in AG and DG concentrations and in appetite during a test meal were studied. Exercise did not significantly affect insulin sensitivity or body weight. Fasting total (AG and DG) ghrelin concentrations were lower in OW (600 +/- 33 pg/ml) compared with NW (764 +/- 33 pg/ml, P exercise. In contrast, there was a differential effect of exercise on both AG and DG (P exercise, and this increase was greater in NW compared with OW adolescents (P Exercise differentially affects AG and DG in NW and OW male adolescents. Our data suggest that total ghrelin does not adequately reflect AG and DG concentrations and that the influence of exercise-induced hormonal changes should be considered to ensure success in weight management.

  5. Struktur Mikroanatomi Hati dan Kadar Kolesterol Total Plasma Darah Tikus Putih Strain Wistar Pasca Suplementasi Minyak Lemuru dan Minyak Sawit

    Directory of Open Access Journals (Sweden)

    Ngudy Jaka Surasa

    2014-09-01

    Full Text Available Mengkonsumsi minyak lemuru dan minyak sawit secara terus menerus, diduga dapat menyebabkan kerusakan mikroanatomi hati. Penelitian ini bertujuan untuk mengetahui struktur mikroanatomi hati dan kadar kolesterol total plasma darah tikus putih strain Wistar paska suplementasi minyak lemuru dan minyak sawit. Penelitian ini merupakan penelitian eksperimental, dengan rancangan acak lengkap. Penelitian menggunakan 25 ekor tikus usia ± 3 bulan. Masing-masing diberi minyak sawit dan minyak lemuru sebanyak 0%+0%, 5%+5%, 10%+10%, 15%+15%, dan 20%+20% secara per oral selama 28 hari. Data kadar kolesterol total plasma darah, berat badan tikus dan berat hati tikus dianalisis secara kuantitatif menggunakan ANAVA satu arah, dengan tingkat kesalahan 5%. Hasil penelitian menunjukkan bahwa pemberian minyak sawit dan minyak lemuru bersifat toksik terhadap hati dan dapat menurunan kadar kolesterol total plasma darah. Sifat toksik minyak lemuru dan minyak sawit terhadap hati dapat dilihat dari adanya perubahan struktur mikroanatomi hati, makroskopis hati tikus, dan berat hati tikus. Kerusakan struktur mikroanatomi hati yang ditemukan berupa kerusakan sel hati (nekrosis hati serta melebarnya sinusoid. Kesimpulan penelitian ini adalah pemberian minyak sawit dan minyak lemuru mengakibatkan kerusakan mikroanatomi berupa nekrosis sel hati, sehingga mempengaruhi makroskopis hati (perubahan tekstur dan warna, berat hati, dan mempengaruhi berat badan tikus.Consuming lemuru oil and palm oil continuously could be expected to cause damage to the liver micro-anatomy. This study aimed to determine the micro-anatomy structure of liver and blood plasma total cholesterol level of white rats Wistar strain by post-oil supplementation of lemuru and palm oil. This research was experimental, with a completely randomized design. The research used 25 mice aged ± 3 months. Each was given a palm oil and lemuru oil as much as 0%+0%, 5%+5%, 10%+10%, 15%+15%, and 20%+20% orally for 28 days

  6. Regulation of gastroduodenal motility: acyl ghrelin, des-acyl ghrelin and obestatin and hypothalamic peptides.

    Science.gov (United States)

    Fujimiya, Mineko; Ataka, Koji; Asakawa, Akihiro; Chen, Chih-Yen; Kato, Ikuo; Inui, Akio

    2012-01-01

    Real-time measurements for gut motility in conscious rats or mice combined with intracerebroventricular or intravenous injection of peptide agonists or antagonists allow us to understand the regulatory mechanism of gastrointestinal motility. Neuropeptide Y (NPY) in the arcuate nucleus in the hypothalamus stimulates the fasted motility in the duodenum, while urocortin in the paraventricular nucleus inhibits fed and fasted motility in the antrum and duodenum. Acyl ghrelin exerts stimulatory effects on the motility of the antrum and duodenum in both the fed and fasted state of animals. NPY Y2 and Y4 receptors in the brain may mediate the action of acyl ghrelin, and vagal afferent pathways might be involved in this mechanism. Des-acyl ghrelin exerts inhibitory effects on the motility of the antrum but not on the motility of the duodenum in the fasted state of animals. CRF type 2 receptor in the brain may mediate the action of des-acyl ghrelin, and vagal afferent pathways might not be involved in this mechanism. Obestatin exerts inhibitory effects on the motility of the antrum and duodenum in the fed state but not in the fasted state of animals. CRF type 1 and type 2 receptors in the brain may mediate the action of obestatin, and vagal afferent pathways might be partially involved in this mechanism.

  7. Diurnal variation in total plasma tryptophan in controls and in depression.

    Science.gov (United States)

    Candito, M; Souêtre, E; Iordache, A; Pringuey, D; Ardisson, J L; Chambon, P; Darcourt, G

    1990-01-01

    Circadian rhythms of total tryptophan were investigated by assays of hourly blood samples over 25 h. The study population consisted of four endogenously depressed patients investigated in the absence of any treatment and six healthy controls. The abnormalities detected by statistical analyses in untreated depression consisted mainly of amplitude reduction; the phase positions of the depressed patients were similar to those of the controls.

  8. Dietary factors associated with plasma high molecular weight and total adiponectin levels in apparently healthy women

    NARCIS (Netherlands)

    Yannakoulia, Mary; Yiannakouris, Nikos; Melistas, Labros; Fappa, Evaggelia; Vidra, Nikoletta; Kontogianni, Meropi D; Mantzoros, Christos S

    2008-01-01

    OBJECTIVE: Our aim was to investigate associations between dietary factors and high molecular weight (HMW) as well as total adiponectin in a sample of apparently healthy adult Mediterranean women. DESIGN AND METHODS: Two hundred and twenty women were enrolled in this study. Anthropometric and body

  9. Role of ghrelin in regulating rabbit ovarian function and the response to LH and IGF-I.

    Science.gov (United States)

    Sirotkin, Alexander V; Rafay, Ján; Kotwica, Ján; Darlak, Krzysztof; Valenzuela, Francisco

    2009-04-01

    The aim of these in vivo and in vitro studies was to examine the role of ghrelin in the control of plasma hormone concentrations, the proliferation, apoptosis and secretory activity of ovarian granulosa cells and the response of these cells to hormonal treatments. Female rabbits were injected with ghrelin (10 microg/animal/day for one week before ovulation induced by 25IU PMSG and 0.25IU LHRH). On the day of ovulation, blood samples were collected and analyzed for concentrations of progesterone (P(4)), testosterone (T), estradiol (E(2)), estrone-sulphate (ES), insulin-like growth factor I (IGF-I) and leptin (L) by RIA. Some control and ghrelin-treated animals were killed in the periovulatory period, their ovaries were weighed and granulosa cells were isolated and cultured for 2d. Cell proliferation (expression of PCNA) and apoptosis (expression of TdT) were evaluated by immunocytochemistry and TUNEL respectively. Secretion of P(4), T, E(2), IGF-I, and prostaglandin F (PGF) by granulosa cells cultured with and without LH or IGF-I (1, 10 or 100 ng/ml medium) was assessed by RIA. The remaining control and treated animals were kept until parturition, while the number, viability and body weight of pups were recorded. Ghrelin treatment increased rabbit plasma T and decreased ES concentrations but did not influence P(4), E(2), IGF-I or L. Granulosa cells from ghrelin-treated animals showed higher expression of PCNA and lower expression of TdT, than those from control animals. They also secreted less P(4), T, E(2), IGF-I and PGF than granulosa cells from untreated animals. Treatment of cultured granulosa cells with ghrelin (1, 10 or 100 ng/ml medium) either increased (at 1 ng/ml) or decreased (at 10 ng/ml) P(4) secretion, increased (at 100 ng/ml) or decreased (at 10 ng/ml) IGF-I secretion, decreased T (at 1 and 10 ng/ml) and OT (at 1 ng/ml) secretion, and increased (at 100 ng/ml) PGF secretion. LH treatment of cells from control animals stimulated P(4) (at 1 and 10 ng

  10. Comparison of the effects of human and chicken ghrelin on chicken ovarian hormone release.

    Science.gov (United States)

    Sirotkin, Alexander V; Harrath, Abdel Halim; Grossmann, Roland

    2016-11-01

    The aim of the present experiments was to examine the species-specific and cell-specific effects of ghrelin on chicken ovarian hormone release. For this purpose, we compared the effects of chicken and human ghrelin on the release of estradiol (E), testosterone (T), progesterone (P) and arginine-vasotocin (AVT) by cultured fragments of chicken ovarian follicles and on the release of T and AVT by cultured ovarian granulosa cells. In cultured chicken ovarian fragments, both human and chicken ghrelin promoted E release. T output was stimulated by chicken ghrelin but not by human ghrelin. No effect of either human or chicken ghrelin on P release was observed. Human ghrelin promoted but chicken ghrelin suppressed AVT release by chicken ovarian fragments. In cultured ovarian granulosa cells, human ghrelin inhibited while chicken ghrelin stimulated T release. Both human and chicken ghrelin suppressed AVT output by chicken granulosa cells. These data confirm the involvement of ghrelin in the control of ovarian secretory activity and demonstrate that the effect of ghrelin is species-specific. The similarity of avian ghrelin on avian ovarian granulosa cells and ovarian fragments (containing both granulosa and theca cells) suggests that ghrelin can influence chicken ovarian hormones primarily by acting on granulosa cells.

  11. Chronic central administration of Ghrelin increases bone mass through a mechanism independent of appetite regulation.

    Directory of Open Access Journals (Sweden)

    Hyung Jin Choi

    Full Text Available Leptin plays a critical role in the central regulation of bone mass. Ghrelin counteracts leptin. In this study, we investigated the effect of chronic intracerebroventricular administration of ghrelin on bone mass in Sprague-Dawley rats (1.5 μg/day for 21 days. Rats were divided into control, ghrelin ad libitum-fed (ghrelin ad lib-fed, and ghrelin pair-fed groups. Ghrelin intracerebroventricular infusion significantly increased body weight in ghrelin ad lib-fed rats but not in ghrelin pair-fed rats, as compared with control rats. Chronic intracerebroventricular ghrelin infusion significantly increased bone mass in the ghrelin pair-fed group compared with control as indicated by increased bone volume percentage, trabecular thickness, trabecular number and volumetric bone mineral density in tibia trabecular bone. There was no significant difference in trabecular bone mass between the control group and the ghrelin ad-lib fed group. Chronic intracerebroventricular ghrelin infusion significantly increased the mineral apposition rate in the ghrelin pair-fed group as compared with control. In conclusion, chronic central administration of ghrelin increases bone mass through a mechanism that is independent of body weight, suggesting that ghrelin may have a bone anabolic effect through the central nervous system.

  12. Analysis of bioethanol samples through Inductively Coupled Plasma Mass Spectrometry with a total sample consumption system

    Science.gov (United States)

    Sánchez, Carlos; Lienemann, Charles-Philippe; Todolí, Jose-Luis

    2016-10-01

    Bioethanol real samples have been directly analyzed through ICP-MS by means of the so called High Temperature Torch Integrated Sample Introduction System (hTISIS). Because bioethanol samples may contain water, experiments have been carried out in order to determine the effect of ethanol concentration on the ICP-MS response. The ethanol content studied went from 0 to 50%, because higher alcohol concentrations led to carbon deposits on the ICP-MS interface. The spectrometer default spray chamber (double pass) equipped with a glass concentric pneumatic micronebulizer has been taken as the reference system. Two flow regimes have been evaluated: continuous sample aspiration at 25 μL min- 1 and 5 μL air-segmented sample injection. hTISIS temperature has been shown to be critical, in fact ICP-MS sensitivity increased with this variable up to 100-200 °C depending on the solution tested. Higher chamber temperatures led to either a drop in signal or a plateau. Compared with the reference system, the hTISIS improved the sensitivities by a factor included within the 4 to 8 range while average detection limits were 6 times lower for the latter device. Regarding the influence of the ethanol concentration on sensitivity, it has been observed that an increase in the temperature was not enough to eliminate the interferences. It was also necessary to modify the torch position with respect to the ICP-MS interface to overcome them. This fact was likely due to the different extent of ion plasma radial diffusion encountered as a function of the matrix when working at high chamber temperatures. When the torch was moved 1 mm plasma down axis, ethanolic and aqueous solutions provided statistically equal sensitivities. A preconcentration procedure has been applied in order to validate the methodology. It has been found that, under optimum conditions from the point of view of matrix effects, recoveries for spiked samples were close to 100%. Furthermore, analytical concentrations for real

  13. Determination of total tin in canned food using inductively coupled plasma atomic emission spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Perring, Loic; Basic-Dvorzak, Marija [Department of Quality and Safety Assurance, Nestle Research Centre, P.O. Box 44, Vers chez-les-Blanc, 1000, Lausanne (Switzerland)

    2002-09-01

    Tin is considered to be a priority contaminant by the Codex Alimentarius Commission. Tin can enter foods either from natural sources, environmental pollution, packaging material or pesticides. Higher concentrations are found in processed food and canned foods. Dissolution of the tinplate depends on the of food matrix, acidity, presence of oxidising reagents (anthocyanin, nitrate, iron and copper) presence of air (oxygen) in the headspace, time and storage temperature. To reduce corrosion and dissolution of tin, nowadays cans are usually lacquered, which gives a marked reduction of tin migration into the food product. Due to the lack of modern validated published methods for food products, an ICP-AES (Inductively coupled plasma-atomic emission spectroscopy) method has been developed and evaluated. This technique is available in many laboratories in the food industry and is more sensitive than atomic absorption. Conditions of sample preparation and spectroscopic parameters for tin measurement by axial ICP-AES were investigated for their ruggedness. Two methods of preparation involving high-pressure ashing or microwave digestion in volumetric flasks were evaluated. They gave complete recovery of tin with similar accuracy and precision. Recoveries of tin from spiked products with two levels of tin were in the range 99{+-}5%. Robust relative repeatabilities and intermediate reproducibilities were <5% for different food matrices containing >30 mg/kg of tin. Internal standard correction (indium or strontium) did not improve the method performance. Three emission lines for tin were tested (189.927, 283.998 and 235.485 nm) but only 189.927 nm was found to be robust enough with respect to interferences, especially at low tin concentrations. The LOQ (limit of quantification) was around 0.8 mg/kg at 189.927 nm. A survey of tin content in a range of canned foods is given. (orig.)

  14. Diurnal Intermittent Fasting during Ramadan: The Effects on Leptin and Ghrelin Levels

    Science.gov (United States)

    Alzoghaibi, Mohammed A.; Pandi-Perumal, Seithikurippu R.; Sharif, Munir M.; BaHammam, Ahmed S.

    2014-01-01

    We aimed to assess the effect of Islamic intermittent fasting, during and outside of Ramadan, on plasma levels of leptin and ghrelin while controlling for several potential confounding variables. Eight healthy male volunteers with a mean age of 26.6±4.9 years reported to the sleep disorders center (SDC) at King Saud University on four occasions: 1) adaptation; 2) 4 weeks before Ramadan while performing Islamic fasting for 1 week (baseline fasting) (BLF); 3) 1 week before Ramadan (non-fasting baseline) (BL); and 4) during the second week of Ramadan while fasting. Plasma leptin and ghrelin levels were measured using enzyme-linked immunoassays at 22:00, 02:00, 04:00, 06:00, and 11:00. During BLF, there were significant reductions in plasma leptin concentrations at 22:00 and 02:00 compared with the baseline concentrations (at 22:00: 194.2±177.2 vs. 146.7±174.5; at 02:00: 203.8±189.5 vs. 168.1±178.1; pfasting may be the result of the changes in meal times during fasting. PMID:24637892

  15. Solid-Sampling Electrothermal Vaporization Inductively Coupled Plasma Optical Emission Spectrometry for Direct Determination of Total Oxygen in Coal.

    Science.gov (United States)

    Vogt, Thomas; Bauer, Daniela; Nennstiel, David; Otto, Matthias

    2015-10-20

    A new analytical method for direct determination of total oxygen contents in eight coal samples of the Argonne Premium Coal (APC) series and in the NIST SRM 1632d is presented. The development of a suitable calibration procedure, optimization of measurement conditions, and the application of a tailored data processing for handling of plasma effects and high blanks enable the quantification of oxygen simultaneously with other trace, minor, or major elements in whole coal samples by means of electrothermal vaporization inductively coupled plasma optical emission spectrometry (ETV-ICP OES). For comparison, the oxygen contents were determined by a direct oxygen analyzer. The obtained oxygen values of the APC and the reference material NIST SRM 1632d were compared to data in the literature. The precision of the ETV-ICP OES was within ±3.5%, and the recovery better than 92%. With this good accuracy, the developed direct solid sampling method ETV-ICP OES is well suited for the fast determination of oxygen in coals, varying in rank from lignite to semianthracite, in a content range of about 100 ppm up to 27% using 1.5 mg sample weight. This direct analysis method represents an accurate, advantageous alternative to currently used methods for estimation of total oxygen contents in coals.

  16. B-type natriuretic peptide modulates ghrelin, hunger, and satiety in healthy men.

    Science.gov (United States)

    Vila, Greisa; Grimm, Gabriele; Resl, Michael; Heinisch, Birgit; Einwallner, Elisa; Esterbauer, Harald; Dieplinger, Benjamin; Mueller, Thomas; Luger, Anton; Clodi, Martin

    2012-10-01

    Chronic heart failure is accompanied by anorexia and increased release of B-type natriuretic peptide (BNP) from ventricular cardiomyocytes. The pathophysiological mechanisms linking heart failure and appetite regulation remain unknown. In this study, we investigated the impact of intravenous BNP administration on appetite-regulating hormones and subjective ratings of hunger and satiety in 10 healthy volunteers. Participants received in a randomized, placebo-controlled, crossover, single-blinded study (subject) placebo once and 3.0 pmol/kg/min human BNP-32 once administered as a continuous infusion during 4 h. Circulating concentrations of appetite-regulating peptides were measured hourly. Subjective ratings of hunger and satiety were evaluated by visual analog scales. BNP inhibited the fasting-induced increase in total and acylated ghrelin concentrations over time (P = 0.043 and P = 0.038, respectively). In addition, BNP decreased the subjective rating of hunger (P = 0.009) and increased the feeling of satiety (P = 0.012) when compared with placebo. There were no significant changes in circulating peptide YY, glucagon-like peptide 1, oxyntomodulin, pancreatic polypeptide, leptin, and adiponectin concentrations. In summary, our results demonstrate that BNP exerts anorectic effects and reduces ghrelin concentrations in men. These data, taken together with the known cardiovascular properties of ghrelin, support the existence of a heart-gut-brain axis, which could be therapeutically targeted in patients with heart failure and obesity.

  17. Altered distribution of Ghrelin protein in mice molar development.

    Science.gov (United States)

    Liu, Bo; Han, Xiuchun; Feng, Wei; Cui, Jian; Hasegawa, Tomoka; Amizuka, Norio; Xu, Xin; Li, Minqi

    2016-05-01

    Ghrelin, an appetite-stimulating hormone, plays diverse regulatory functions in cell growth, proliferation, differentiation and apoptosis during mammalian development. There is limited information currently available regarding Ghrelin expression during mammalian tooth development, thus we aimed to establish the spatiotemporal expression of Ghrelin during murine molar odontogenesis. Immunohistochemistry was performed to detect the expression pattern of Ghrelin in mandible molar from E15.5 to PN7 during murine tooth development. The results showed that Ghrelin initially expressed in the inner enamel epithelium and the adjacent mesenchymal cells below, further with persistent expression in the ameloblasts and odontoblasts throughout the following developmental stages. In addition, Ghrelin was also present in Hertwig's epithelial root sheath at the beginning of tooth root formation. These results suggest that Ghrelin was present in tooth organs throughout the stages of tooth development, especially in ameloblasts and odontoblasts with little spatiotemporal expression differences. However, the potential regulatory roles of this hormone in tooth development still need to be validated by functional studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Ghrelin and leptin pathophysiology in chronic kidney disease.

    Science.gov (United States)

    Gunta, Sujana S; Mak, Robert H

    2013-04-01

    Ghrelin is an orexigenic hormone with additional effects on the regulation of inflammation and the cardiovascular system. It may play an important role in the pathogenesis of cachexia/protein-energy wasting (PEW), inflammation and cardiovascular complications in chronic kidney disease (CKD). There are three circulating gene products of ghrelin, namely, acyl ghrelin, des-acyl ghrelin and obestatin, each with individual distinct functions. Perturbations of these circulating ghrelin proteins impact the overall milieu of CKD. Leptin is an anorexigenic hormone which is secreted from the adipocytes and interacts with ghrelin and other appetite-regulating hormones. Leptin also plays a role in regulating inflammation and the cardiovascular system. Indeed, ghrelin and leptin may play yin-and-yang roles in CKD pathophysiology. Clinical trials involving the use of the mimetics or antagonists of these hormones are limited to short-term phase I/II studies. Further understanding of their interactions in CKD pathophysiology is needed for potential large-scale clinical trials, which may impact the quality of life and survival of patients with CKD.

  19. The endocrine effects of acylated and des-acylated ghrelin

    Directory of Open Access Journals (Sweden)

    St-Pierre DH

    2012-08-01

    Full Text Available David E Andrich,1 Katherine Cianflone,2 Alain-Steve Comtois,1 Simon Lalonde,1 David H St-Pierre11Department of Kinesiology, Université du Québec à Montréal (UQAM, Montreal, Canada; 2Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, CanadaAbstract: Acylated ghrelin is one of the few peptides known whose isolation and characterization follow the description of its receptor and its basic biological functions. Characterized initially for its somatotrophic properties, ghrelin was shown later to exert various effects on other important physiological functions in mammals, such as appetite, gastric acid secretion, gut motility, insulin sensitivity, adiposity, and energy expenditure. Further, ghrelin influences cardiac function, reproduction, and the immune system as well. Here we present an overview of the discovery and subsequent development of ghrelin as an important peptide hormone involved in the control of energy metabolism in humans and other mammals. Recently reported effects of acylated ghrelin on glucose/lipid uptake, de novo lipogenesis, gluconeogenesis, lipid-droplet formation, fatty acid transport into mitochondria, and mitochondrial activity are particularly emphasized and discussed.Keywords: Acylated ghrelin, des-acylated ghrelin, physiological functions, adipogenesis

  20. Low serum levels of ghrelin are associated with gallstone disease

    Institute of Scientific and Technical Information of China (English)

    Nahum Méndez-Sánchez; Martha H Ramos; Héctor A Baptista-González; Misael Uribe; Guadalupe Ponciano-Rodríguez; Luisa Bermejo-Martínez; Antonio R Villa; Norberto C Chávez-Tapia; Daniel Zamora-Valdés; Raúl Pichardo-Bahena; Blanca Barredo-Prieto; Martha H Uribe-Ramos

    2006-01-01

    AIM: To explore the role of ghrelin in gallstone disease.METHODS: We carried out a cross-sectional study in 150 subjects, 38 with gallstones (cases) and 112 controls. We also did a real-time PCR-RT study in twenty gallbladder samples each. Body mass index (BMI),serum insulin, ghrelin, and serum lipids were measured.Logistic regression analyses (univariate and multivariate) were conducted to estimate the probability of gallstone disease associated with serum ghrelin concentrations.RESULTS: Cases were statistically different from controls in gender distribution (P = 0.01), age (53 vs 44 yr, P = 0.002), BMI (28 vs 25; P = 0.004), and glucose (5.26 vs 4.98 mmol/L; P = 0.05). The prevalence of ghrelin serum levels above the third tercile was lower in subjects without metabolic syndrome (P < 0.05). In a multivariate model, we found a protective effect, when ghrelin values were higher than the median value (OR = 0.27, 95%CI 0.09-0.82, P = 0.02). Twenty (20%) gallbladder specimens expressed ghrelin mRNA.CONCLUSION: Serum ghrelin concentrations are associated with a protective effect of GD.

  1. Ghrelin and its therapeutic potential for cachectic patients.

    Science.gov (United States)

    Ashitani, Jun-ichi; Matsumoto, Nobuhiro; Nakazato, Masamitsu

    2009-10-01

    The discovery of ghrelin has resulted in the development of approaches to appetite, enabling a better understanding of the mechanisms regulating appetite through molecular analyses. Ghrelin is a 28-amino acid peptide that was isolated from the stomach only a decade ago, and has recently been investigated as a potential therapeutic endogenous agent. This peptide increases appetite, adjusts energy balance, suppresses inflammation, and enhances the release of growth hormone from the pituitary gland. Although many bioactive substances such as peptide YY, leptin, adiponectin and obestatin are involved in appetite control, ghrelin is the only known peptide to signal starvation information from a peripheral organ to the central nervous system, contributing to an increase in appetite. Clinical trials have revealed the effectiveness of ghrelin in increasing lean body mass and activity in cachectic patients. As shown in clinical research on humans and basic research using animal models, cachexia often occurs in response to excess release of proinflammatory cytokines and induces further appetite loss, which aggravates the physiological status of underlying diseases. Ghrelin functions as a protector against the vicious cycle of the cachectic paradigm through orexigenic, anabolic and anti-inflammatory effects, so administration of ghrelin may be able to improve quality of life in cachectic patients. We show here a significant role of ghrelin in the pathophysiology of cachectic diseases and the possibility of clinical applications.

  2. Sulfated gastrin stimulates ghrelin and growth hormone release but inhibits insulin secretion in cattle.

    Science.gov (United States)

    Zhao, Hongqiong; Yannaing, Swe; Thanthan, Sint; Kuwayama, Hideto

    2011-11-01

    This study was designed to determine the effects of gastrin on the circulating levels of ghrelin, growth hormone (GH), insulin, glucagon and glucose in ruminants. Two experiments were done in eight Holstein steers. Animals were randomly assigned to receive intravenous bolus injections: (1) 0.1% bovine serum albumin in saline as vehicle, 0.8, 4.0 and 20.0 μg/kg body weight (BW) of bovine sulfated gastrin-34; (2) vehicle, 0.53 μg/kg BW of bovine sulfated gastrin-17 alone or combined with 20.0 μg/kg BW of [D-Lys(3)]-GHRP-6, the selective antagonist of GHS-R1a. Blood samples were collected from -10 to 150 min relative to injection time. Concentrations of acyl and total ghrelin in response to gastrin-34 injection were significantly increased in a dose-dependent manner. Concentrations of GH were also markedly elevated by gastrin-34 injection; however, the effect of 20.0 μg/kg was weaker than that of 4.0 μg/kg. The three doses of gastrin-34 equally decreased insulin levels within 15 min and maintained the level until the time of last sampling. Gastrin-34 had no effect (P > 0.05) on the levels of glucagon and glucose. Levels of acyl ghrelin increased after administration of gastrin-17 alone or combined with [D-Lys(3)]-GHRP-6; however, [D-Lys(3)]-GHRP-6 did not block the elevation of GH by gastrin-17. The present results indicate that sulfated gastrin stimulates both ghrelin and GH release, but the GHS-R1a may not contribute to the release of GH by gastrin. Moreover, sulfated gastrin seems to indirectly maintain the homeostasis of blood glucose through the down-regulation of insulin in ruminants.

  3. Menstrual irregularities and energy deficiency in physically active women: the role of ghrelin, PYY and adipocytokines.

    Science.gov (United States)

    Scheid, Jennifer L; De Souza, Mary Jane

    2010-01-01

    Menstrual cycle irregularities are often observed among physically active women and athletes who participate in physical activity ranging from recreational to competitive exercise training. Further, such irregularities have been casually linked to an energy deficiency where caloric intake is inadequate for exercise energy expenditure resulting in a suppressive effect on growth and reproduction. Adaptations consistent with chronic energy deficiency, including reductions in resting energy expenditure and total triiodothyronine, have been observed in exercising women with functional hypothalamic amenorrhea (FHA). Gut peptides and adipocytokines also appear to be altered in exercising women with FHA and have been hypothesized to be involved in the etiology of FHA. Ghrelin concentrations are elevated in exercising women with FHA. Interestingly, while fasting ghrelin, an orexigenic peptide, is elevated in women with FHA, PYY, an orexigenic peptide, is paradoxically also elevated in women with anorexia nervosa and exercising women with FHA. Leptin, an adipocytokine, is also suppressed in FHA associated with exercise and anorexia. A critical leptin concentration threshold is suggested to be necessary for regular menses to occur. Ghrelin, PYY, and leptin all have the ability to cross the blood brain barrier and, in the hypothalamus, can modulate appetite and food intake, and are hypothesized to affect the hypothalamic-pituitary-ovarian axis. Future studies are needed to determine if ghrelin, PYY, or leptin play a direct role in the regulation of the hypothalamic-pituitary-ovarian axis, and if these signals can be altered by improving energy status secondary to increasing caloric intake and initiate the reversal of amenorrhea. Copyright © 2010 S. Karger AG, Basel.

  4. Increased peptide YY blood concentrations, not decreased acyl-ghrelin, are associated with reduced hunger and food intake in healthy older women: Preliminary evidence.

    Science.gov (United States)

    Hickson, Mary; Moss, Charlotte; Dhillo, Waljit S; Bottin, Jeanne; Frost, Gary

    2016-10-01

    With ageing there is frequently a loss of appetite, termed anorexia of ageing, which can result in under-nutrition. We do not know how appetite control alters with ageing. The objective of this study was to investigate whether differences in the release of, and response to, gastrointestinal appetite hormones is altered in young compared to old healthy volunteers. We hypothesised that an increase in PYY and GLP-1 or a decrease ghrelin may result in a decreased appetite. A comparative experimental design, using a cross-sectional sample of ages from a healthy population, matched for sex and BMI was used. The study compared total ghrelin, acyl-ghrelin, PYY, GLP-1 and subjective appetite responses to ingestion of a standardised 2781kj (660 kcal) test meal. 31 female volunteers aged between 21 and 92yrs took part. Multiple linear regression showed that both age and sex had an independent effect on energy intake. Subjective appetite scores showed that hunger, pleasantness to eat, and prospective food intake were significantly lower in the older age groups. PYY incremental area under the curve (IAUC) was greater in the oldest old compared to younger ages f(3,27) = 2.9, p = 0.05. No differences in GLP-1, ghrelin or acyl-ghrelin were observed in the older compared to younger age groups. Our data suggest that there may be increases in postprandial PYY(3-36) levels in female octogenarians, potentially resulting in reduced appetite. There does not appear to be any change in ghrelin or acyl-ghrelin concentrations with ageing.

  5. Reference interval determination of total plasma homocysteine in an Indian population.

    Science.gov (United States)

    Lahiri, Kapil D; Datta, Himadri; Das, Harendra N

    2014-01-01

    Hyperhomocysteinemia has been shown to be an independent risk factor for cardiovascular disease as well as retinal vascular occlusion. Because of the epidemiological, dietary, genetic and environmental diversity among the different countries, each country should establish the reference interval of homocysteine of their own population for recommending appropriate medical decision limits. Hence a total of 1,288 apparently healthy subjects including 636 male and 652 female were enrolled in the present study to determine the reference intervals of homocysteine in an Indian population. Results of the study were presented as mean, standard deviation, median and 2.5th and 97.5th percentile with the 0.90 confidence interval of each percentile values of homocysteine along with decade-wise changes.

  6. A high-protein diet increases postprandial but not fasting plasma total homocysteine concentrations: A dietary controlled, crossover trial in healthy volunteers

    NARCIS (Netherlands)

    Verhoef, P.; Vliet, T. van; Olthof, M.R.; Katan, M.B.

    2005-01-01

    Background: A high plasma concentration of total homocysteine (tHcy) is associated with increased risk of cardiovascular disease. A high protein intake and hence a high intake of methionine-the sole dietary precursor of homocysteine-may raise plasma tHcy concentrations. Objectives: We studied whethe

  7. Evaluation of immunohistochemical expression of ghrelin-producing rectal cells in Wistar rats receiving the cafeteria diet.

    Science.gov (United States)

    Lyra, Humberto Fenner; Schiavon, Leonardo de Lucca; Vieira, Daniella Serafin Couto; Teive, André Muller; Costa, Aline; Onzi, Tiago Rafael; Nau, Angélica Luciana; d'Acampora, Armando José

    2013-08-01

    To investigate the impact of cafeteria diet on ghrelin expression in rectal tissue and identify the morphologic cell type. Twenty-four male Wistar rats were divided into four subgroups of six animals each: RC1 (rat chow 1) and CAF1 (cafeteria diet 1) for a period of 30 days; RC2 (rat chow 2) and CAF2 (cafeteria diet 2) for a period of 60 days. The animal and rectal weight, the number and the type of immunoreactive ghrelin cells were recorded and compared between the subgroups. The statistical study was established by ANOVA and Student's t test. There was no difference in the total of immunoreactive cells (p=0.685) between the subgroups nor between weight and presence or absence of ghrelin expression (p=0.993). All the immunoreactive cells identified were closed-type. The cafeteria diet did not have influence on the amount of immunoreactive rectal cells of ghrelin and only one type (closed-type) of immunoreactive cells was expressed in the rectum.

  8. Effects of ghrelin on food intake and neuroendocrine function in sheep.

    Science.gov (United States)

    Sugino, T; Hasegawa, Y; Kurose, Y; Kojima, M; Kangawa, K; Terashima, Y

    2004-07-01

    Ghrelin, a novel acylated peptide, is the endogenous ligand for growth hormone secretagogue (GHS) receptor. Ghrelin is produced mainly in the oxyntic glands of the stomach, but also produced in the intestines, kidneys, hypothalamus and pituitary gland. Circulating ghrelin levels have been shown to rise before a meal and fall afterwards, suggesting that anticipation of a meal may stimulate secretion. In some species, ghrelin administration has been shown to stimulate growth hormone (GH) secretion, and to cause weight gain by increasing food intake and reducing metabolic utilization of fat. Furthermore, intracerebroventricular and intravascular administration of ghrelin increases gastric acid output in a dose-dependent manner. Thus, ghrelin may play an important role in controlling feeding behavior and energy homeostasis. We have investigated the role of ghrelin in the control of feeding and neuroendocrine function in ruminants using sheep as an experimental model. This mini review describes mechanisms regulating ghrelin secretion at feeding time, and also focuses on the neuroendocrine functions of ghrelin.

  9. The regulation of circulating ghrelin - with recent updates from cell-based assays.

    Science.gov (United States)

    Iwakura, Hiroshi; Kangawa, Kenji; Nakao, Kazuwa

    2015-01-01

    Ghrelin is a stomach-derived orexigenic hormone with a wide range of physiological functions. Elucidation of the regulation of the circulating ghrelin level would lead to a better understanding of appetite control in body energy homeostasis. Earlier studies revealed that circulating ghrelin levels are under the control of both acute and chronic energy status: at the acute scale, ghrelin levels are increased by fasting and decreased by feeding, whereas at the chronic scale, they are high in obese subjects and low in lean subjects. Subsequent studies revealed that nutrients, hormones, or neural activities can influence circulating ghrelin levels in vivo. Recently developed in vitro assay systems for ghrelin secretion can assess whether and how individual factors affect ghrelin secretion from cells. In this review, on the basis of numerous human, animal, and cell-based studies, we summarize current knowledge on the regulation of circulating ghrelin levels and enumerate the factors that influence ghrelin levels.

  10. Total iodine in infant formula and nutritional products by inductively coupled plasma/mass spectrometry: First Action 2012.14.

    Science.gov (United States)

    Pacquette, Lawrence H; Levenson, Alan M; Thompson, Joseph J; Dowell, Dawn

    2013-01-01

    After an assessment of data generated from a single-laboratory validation study published in the Journal of AOAC INTERNATIONAL 95, 169-176 (2012), a method for determining the total level of iodine in infant formula and nutritional products was presented for consideration for adoption by AOAC during the AOAC Annual Meeting held September 30-October 3, 2012 in Las Vegas, NV. An Expert Review Panel on Infant Formula and Adult Nutritionals concluded that the method met the established standard method performance requirements, and approved the method as AOAC Official First Action. The method involves digestion of the sample with nitric acid in a closed vessel microwave oven, followed by determination by inductively coupled plasma/MS using tellurium as the internal standard. The method LOQ for total iodine was 1.5 microg/100 g, but a practical LOQ was used at 5 microg/100 g total iodine. The analytical range of the method was 5-100 microg/100 g total iodine. The recoveries from 15 spiked nutritional products ranged from 90 to 105%.

  11. Genetic manipulation of the ghrelin signaling system in male mice reveals bone compartment specificity of acylated and unacylated ghrelin in the regulation of bone remodeling

    Science.gov (United States)

    Ghrelin receptor-deficient (Ghsr-/-) mice that lack acylated ghrelin (AG) signaling retain a metabolic response to unacylated ghrelin (UAG). Recently, we showed that Ghsr-deficiency affects bone metabolism. The aim of this study was to further establish the impact of AG and UAG on bone metabolism. W...

  12. Ghrelin and melatonin as biomarkers in patients with giardiasis

    Directory of Open Access Journals (Sweden)

    Saleem Khteer Al-Hadraawy

    2016-05-01

    Full Text Available Giardia is the most frequently reported intestinal parasite worldwide. The aim of this study was to investigate the ghrelin, melatonin, glucose and cholesterol concentration in male patients infected with Giardia lamblia. We enrolled 66 patients with Giardiasis and the control groups consisted of healthy subjects (n = 30. The results demonstrated that there was a significant decrease (P < 0.05 in ghrelin levels, while the melatonin, glucose and cholesterol levels were significantly increased (P < 0.05 in giardiasis patients as compared to the healthy group. The obtained results suggest that ghrelin and melatonin could serve as biomarkers in patients infected with G. lamblia.

  13. Glutamine-supplemented total parenteral nutrition attenuates plasma interleukin-6 in surgical patients with lower disease severity

    Institute of Scientific and Technical Information of China (English)

    Ming-Tsan Lin; Sung-Pao Kung; Sung-Ling Yeh; Koung-Yi Liaw; Ming-Yang Wang; Ming-Liang Kuo; Po-Houng Lee; Wei-Jao Chen

    2005-01-01

    AIM: To evaluate whether the effect of Gln dipeptideenriched total parenteral nutrition (TPN) on postoperative cytokine alteration depended on the disease severity of surgical patients.METHODS: Forty-eight patients with major abdominal surgery were allocated to two groups to receive isonitrogenous (0.228 g nitrogen/kg per d) and isocaloric(30 kcal/kg per d) TPN for 6 d. Control group (Conv)using conventional TPN solution received 1.5 g amino adds/kg per day, whereas the test group received 0.972 g amino acids/kg per day and 0.417 g L-alanyl-L-glutamine(Ala-Gln)/kg per day. Blood samples were collected on d 1 and d 6 postoperatively for plasma interleukin (IL)-2,IL-6, IL-8, and interferon (IFN)-γ analysis.RESULTS: Plasma IL-2 and IFN-γ were not detectable.IL-6 concentrations were significantly lower on the 6th postoperative day in the Ala-Gln group than those in the Conv group in patients with APACHE Ⅱ≤6, whereas no difference was noted in patients with APACHE Ⅱ>6. There was no difference in IL-8 levels between the two groups.No difference in cumulative nitrogen balance was observed on d 2-5 after the operation between the two groups(Ala-Gln -3.2±1.6 g vs Conv -6.5±2.7 g). A significant inverse correlation was noted between plasma IL-6 levels and cumulative nitrogen balance postoperatively in the Ala-Gln group, whereas no such correlation was observed in the Conv group.CONCLUSION: TPN supplemented with Gln dipeptide had no effect on plasma IL-8 levels after surgery. However,Gln supplementation had a beneficial effect on decreasing systemic IL-6 production after surgery in patients with low admission illness severity, and lower plasma IL-6 may improve nitrogen balance in patients with abdominal surgery when Gln was administered.

  14. Ghrelin differentially modulates the GH secretory response to GHRH between the fed and fasted states in sheep.

    Science.gov (United States)

    Takahashi, H; Kurose, Y; Suzuki, Y; Kojima, M; Yamaguchi, T; Yoshida, Y; Ogino, M; Hodate, K; Azuma, Y; Sugino, T; Kojima, M; Kangawa, K; Hasegawa, Y; Kobayashi, S

    2009-07-01

    The effect of energy balance on the growth hormone (GH) secretory responsiveness to growth hormone-releasing hormone (GHRH) has not been determined in ruminant animals. Therefore, we examined the effects of intravenous injections of 0, 3.3, and 6.6 microg ghrelin/kg body weight (BW), with and without GHRH at 0.25 microg/kg BW, on GH secretory responsiveness in both the fed and fasted sheep. The injections were carried out at 48 h (Fasting state) and 3h (Satiety state) after feeding. Blood samples were taken every 10 minutes, from 30 minutes before to 120 minutes after the injection. Low (3.3 microg/kg BW) and high (6.6 microg/kg BW) doses of ghrelin stimulated GH secretion significantly (Pghrelin stimulated GH secretion significantly (PGhrelin and GHRH exerted a synergistic effect in the Satiety state, but not in the Fasting state. Plasma ghrelin levels were maintained significantly (Pghrelin administration. Plasma free fatty acid (FFA) concentrations were significantly (Pghrelin differentially modulates GH secretory response to GHRH according to feeding states in ruminant animals.

  15. 甲状腺毒症小鼠外周循环中Ghrelin水平的影响因素分析%Effects of Thyrotoixicosis on Circulating Ghrelin Levels in Mice

    Institute of Scientific and Technical Information of China (English)

    李玉姝; 刘通; 付志民; 单忠艳; 滕卫平

    2012-01-01

    Objective To investigate whether thyroitoxicosis would induce changes of plasma ghrelin concentrations in mice and the influencing factors. Methods C57B1/6 mice were treated with thyroxin to induce thyroitoxicosis in experimental group,and then they were further divided into ad libtum, mild and server food restricted groups. Serum glucose,lipid,leptin,GH,IGF-1 and insulin were measured. Plasma ghrelin and Desacyl ghrelin were also detected by EDSA. Results Although the thyroid hormone was in the same level,plasma ghrelin levels showed opposite changes between ad libtum and food restricted thyroitoxicosis mice. Comparing with the control group, Desacyl ghrelin was significantly lower in ad libtum thyroitoxicosis mice,and acylated ghrelin was significantly higher in food restricted thyroitoxicosis mice (P < 0.05). Plasma ghrelin showed a positive correlation with blood glucose and a negative correlation with final body weight,serum insulin,leptin and HOMA-IR index (P < 0.05). Multiple regression analysis showed that glucose and leptin were the predictors for acylated ghrelin levels in thyroid dysfunction. Conclusion These results suggested that thyroid hormone might not be the primary factor regulating ghrelin secretion. The combination of altered metabolic parameters related to glucose metabolic and insulin resistance might be responsible for the alteration of ghrelin concentrations in the situation of thyroid dysfunction.%目的 探讨甲状腺毒症小鼠循环中Ghrelin水平变化及其影响因素.方法 实验组C57BL6小鼠给予左旋甲状腺激素,每日皮下注射,连续2周诱发小鼠甲状腺毒症,对照组仅注射生理盐水.检测小鼠给药前后体质量、摄食量并采血和留尿.测定空腹血糖、血脂、胰岛素、瘦素水平和甲状腺功能等.实验组小鼠进一步分为自由摄食组、轻度限制摄食组及重度限制摄食组.ELISA方法测定血浆辛酰化和去辛酰化Ghrelin水平.结果 与对照组比较,自由

  16. Molecular Cloning of Ghrelin and Characteristics of Ghrelin-Producing Cells in the Gastrointestinal Tract of the Common Marmoset (Callithrix jacchus).

    Science.gov (United States)

    Takemi, Shota; Sakata, Ichiro; Apu, Auvijit Saha; Tsukahara, Shinji; Yahashi, Satowa; Katsuura, Goro; Iwashige, Fumihiro; Akune, Atsushi; Inui, Akio; Sakai, Takafumi

    2016-10-01

    Ghrelin was first isolated from human and rat as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R). In the present study, we determined the ghrelin cDNA sequence of the common marmoset (Callithrix jacchus), a small-bodied New World monkey, and investigated the distribution of ghrelin-producing cells in the gastrointestinal tract and localization profiles with somatostatin-producing cells. The marmoset ghrelin cDNA coding region was 354 base pairs, and showed high homology to that in human, rhesus monkey, and mouse. Marmoset ghrelin consists of 28 amino acids, and the N-terminal region is highly conserved as found in other mammalian species. Marmoset preproghrelin and mature ghrelin have 86.3% and 92.9% homology, respectively, to their human counterparts. Quantitative RT-PCR analysis showed that marmoset ghrelin mRNA is highly expressed in the stomach, but it is not detected in other tissues of the gastrointestinal tract. In addition, a large number of ghrelin mRNA-expressing cells and ghrelin-immunopositive cells were detected in the mucosal layer of the stomach, but not in the myenteric plexus. Moreover, all the ghrelin cells examined in the stomach were observed to be closed-type. Double staining showed that somatostatin-immunopositive cells were not co-localized with ghrelin-producing cells; however, a subset of somatostatin-immunopositive cells is directly adjacent to ghrelin-immunopositive cells. These findings suggest that the distribution of ghrelin cells in marmoset differs from that in rodents, and thus the marmoset may be a more useful model for the translational study of ghrelin in primates. In conclusion, we have clarified the expression and cell distribution of ghrelin in marmoset, which may represent a useful model in translational study.

  17. Anti-obesity and anti-hyperglycemic effects of cinnamaldehyde via altered ghrelin secretion and functional impact on food intake and gastric emptying.

    Science.gov (United States)

    Camacho, Susana; Michlig, Stephanie; de Senarclens-Bezençon, Carole; Meylan, Jenny; Meystre, Julie; Pezzoli, Maurizio; Markram, Henry; le Coutre, Johannes

    2015-01-21

    Cinnamon extract is associated to different health benefits but the active ingredients or pathways are unknown. Cinnamaldehyde (CIN) imparts the characteristic flavor to cinnamon and is known to be the main agonist of transient receptor potential-ankyrin receptor 1 (TRPA1). Here, expression of TRPA1 in epithelial mouse stomach cells is described. After receiving a single-dose of CIN, mice significantly reduce cumulative food intake and gastric emptying rates. Co-localization of TRPA1 and ghrelin in enteroendocrine cells of the duodenum is observed both in vivo and in the MGN3-1 cell line, a ghrelin secreting cell model, where incubation with CIN up-regulates expression of TRPA1 and Insulin receptor genes. Ghrelin secreted in the culture medium was quantified following CIN stimulation and we observe that octanoyl and total ghrelin are significantly lower than in control conditions. Additionally, obese mice fed for five weeks with CIN-containing diet significantly reduce their cumulative body weight gain and improve glucose tolerance without detectable modification of insulin secretion. Finally, in adipose tissue up-regulation of genes related to fatty acid oxidation was observed. Taken together, the results confirm anti-hyperglycemic and anti-obesity effects of CIN opening a new approach to investigate how certain spice derived compounds regulate endogenous ghrelin release for therapeutic intervention.

  18. Are hungry sheep more pessimistic? The effects of food restriction on cognitive bias and the involvement of ghrelin in its regulation.

    Science.gov (United States)

    Verbeek, Else; Ferguson, Drewe; Lee, Caroline

    2014-01-17

    Food restriction is considered to be a welfare issue in extensively reared animals. However, the effects of food restriction on the affective state, and its physiological regulation, are unknown. In Experiment 1, we aimed to assess the effects of increased plasma concentrations of acyl-ghrelin on judgement bias (an indicator of affective states) by fasting sheep for 24h or by ghrelin administration. In Experiment 2, we aimed to assess the effects of chronic food restriction on judgement bias and attention bias towards a food-related cue. For the judgement bias test, sheep were trained in an arena to approach a positive location cue associated with conspecifics and not approach a negative location cue associated with a dog. Three non-trained, non-reinforced ambiguous location cues were situated between the positive and negative locations. Attention bias towards a food-related cue was assessed by placing an empty food bucket against the wall of the arena halfway between the entry point and the positive location. In Experiment 1, sheep were divided into three treatments; 24h fast, ghrelin administration or control. Judgement bias, locomotor activity and plasma cortisol concentrations were assessed. The ghrelin treated group tended to express a more pessimistic bias compared to the control group (Pbias (Pbias and attention bias towards a food-related cue which may indicate altered affective states of sheep.

  19. Prospective Study of Surgical Treatment of Acromegaly: Effects on Ghrelin, Weight, Adiposity, and Markers of CV Risk

    Science.gov (United States)

    Reyes-Vidal, Carlos; Fernandez, Jean Carlos; Bruce, Jeffrey N.; Crisman, Celina; Conwell, Irene M.; Kostadinov, Jane; Geer, Eliza B.; Post, Kalmon D.

    2014-01-01

    Context: Although epidemiological studies have found that GH and IGF-1 normalization reduce the excess mortality of active acromegaly to expected rates, cross-sectional data report some cardiovascular (CV) risk markers to be less favorable in remission than active acromegaly. Objective: The objective of the study was to test the hypothesis that remission of acromegaly after surgical therapy increases weight and adiposity and some CV risk markers and these changes are paralleled by a rise in ghrelin. Design: Forty-two adults with untreated, active acromegaly were studied prospectively. Changes in outcome measures from before to after surgery were assessed in 26 subjects achieving remission (normal IGF-1) and 16 with persistent active acromegaly (elevated IGF-1) after surgery. Setting: The study was conducted at tertiary referral centers for pituitary tumors. Main Outcome Measures: Endocrine, metabolic, and CV risk parameters, anthropometrics, and body composition by dual-energy X-ray absorptiometry were measured. Results: Remission increased total ghrelin, body weight, waist circumference, C-reactive protein, homocysteine, high-density lipoprotein, and leptin and reduced systolic blood pressure, homeostasis model assessment score, triglycerides, and lipoprotein (a) by 6 months and for 32 ± 4 months after surgery. The ghrelin rise correlated with the fall in the levels of GH, IGF-1, and insulin and insulin resistance. Weight, waist circumference, and ghrelin did not increase significantly in the persistent active acromegaly group. Total body fat, trunk fat, and perentage total body fat increased by 1 year after surgery in 15 remission subjects: the increase in body fat correlated with the rise in total ghrelin. Conclusions: Although most markers of CV risk improve with acromegaly remission after surgery, some markers and adiposity increase and are paralleled by a rise in total ghrelin, suggesting that these changes may be related. Understanding the mechanisms and

  20. Interactions of Gastrointestinal Peptides: Ghrelin and Its Anorexigenic Antagonists

    Directory of Open Access Journals (Sweden)

    Anna-Sophia Wisser

    2010-01-01

    Full Text Available Food intake behaviour and energy homeostasis are strongly regulated by a complex system of humoral factors and nerval structures constituting the brain-gut-axis. To date the only known peripherally produced and centrally acting peptide that stimulates food intake is ghrelin, which is mainly synthesized in the stomach. Recent data indicate that the orexigenic effect of ghrelin might be influenced by other gastrointestinal peptides such as cholecystokinin (CCK, bombesin, desacyl ghrelin, peptide YY (PYY, as well as glucagon-like peptide (GLP. Therefore, we will review on the interactions of ghrelin with several gastrointestinal factors known to be involved in appetite regulation in order to elucidate the interdependency of peripheral orexigenic and anorexigenic peptides in the control of appetite.

  1. Interactions of Gastrointestinal Peptides: Ghrelin and Its Anorexigenic Antagonists

    Science.gov (United States)

    Wisser, Anna-Sophia; Habbel, Piet; Wiedenmann, Bertram; Klapp, Burghard F.; Mönnikes, Hubert; Kobelt, Peter

    2010-01-01

    Food intake behaviour and energy homeostasis are strongly regulated by a complex system of humoral factors and nerval structures constituting the brain-gut-axis. To date the only known peripherally produced and centrally acting peptide that stimulates food intake is ghrelin, which is mainly synthesized in the stomach. Recent data indicate that the orexigenic effect of ghrelin might be influenced by other gastrointestinal peptides such as cholecystokinin (CCK), bombesin, desacyl ghrelin, peptide YY (PYY), as well as glucagon-like peptide (GLP). Therefore, we will review on the interactions of ghrelin with several gastrointestinal factors known to be involved in appetite regulation in order to elucidate the interdependency of peripheral orexigenic and anorexigenic peptides in the control of appetite. PMID:20798884

  2. Interactions of gastrointestinal peptides: ghrelin and its anorexigenic antagonists.

    Science.gov (United States)

    Wisser, Anna-Sophia; Habbel, Piet; Wiedenmann, Bertram; Klapp, Burghard F; Mönnikes, Hubert; Kobelt, Peter

    2010-01-01

    Food intake behaviour and energy homeostasis are strongly regulated by a complex system of humoral factors and nerval structures constituting the brain-gut-axis. To date the only known peripherally produced and centrally acting peptide that stimulates food intake is ghrelin, which is mainly synthesized in the stomach. Recent data indicate that the orexigenic effect of ghrelin might be influenced by other gastrointestinal peptides such as cholecystokinin (CCK), bombesin, desacyl ghrelin, peptide YY (PYY), as well as glucagon-like peptide (GLP). Therefore, we will review on the interactions of ghrelin with several gastrointestinal factors known to be involved in appetite regulation in order to elucidate the interdependency of peripheral orexigenic and anorexigenic peptides in the control of appetite.

  3. Ghrelin drives GH secretion during fasting in man

    NARCIS (Netherlands)

    A.F. Muller (Alex); S.W.J. Lamberts (Steven); L.J. Hofland (Leo); M. Bidlingmaier (Martin); C.J. Strasburger; E. Ghigo (Ezio); A-J. van der Lely (Aart-Jan); J.A.M.J.L. Janssen (Joseph); P.M. van Koetsveld (Peter)

    2002-01-01

    textabstractOBJECTIVES: In humans, fasting leads to elevated serum GH concentrations. Traditionally, changes in hypothalamic GH-releasing hormone and somatostatin release are considered as the main mechanisms that induce this elevated GH secretion during fasting. Ghrelin is an

  4. Oral 'hydrogen water' induces neuroprotective ghrelin secretion in mice.

    Science.gov (United States)

    Matsumoto, Akio; Yamafuji, Megumi; Tachibana, Tomoko; Nakabeppu, Yusaku; Noda, Mami; Nakaya, Haruaki

    2013-11-20

    The therapeutic potential of molecular hydrogen (H₂) is emerging in a number of human diseases and in their animal models, including in particular Parkinson's disease (PD). H₂ supplementation of drinking water has been shown to exert disease-modifying effects in PD patients and neuroprotective effects in experimental PD model mice. However, H₂ supplementation does not result in detectable changes in striatal H₂ levels, indicating an indirect effect. Here we show that H₂ supplementation increases gastric expression of mRNA encoding ghrelin, a growth hormone secretagogue, and ghrelin secretion, which are antagonized by the β1-adrenoceptor blocker, atenolol. Strikingly, the neuroprotective effect of H₂ water was abolished by either administration of the ghrelin receptor-antagonist, D-Lys(3) GHRP-6, or atenolol. Thus, the neuroprotective effect of H₂ in PD is mediated by enhanced production of ghrelin. Our findings point to potential, novel strategies for ameliorating pathophysiology in which a protective effect of H₂ supplementation has been demonstrated.

  5. Association of cord blood des-acyl ghrelin with birth weight, and placental GHS-R1 receptor expression in SGA, AGA, and LGA newborns.

    Science.gov (United States)

    González-Domínguez, Martha I; Lazo-de-la-Vega-Monroy, Maria-Luisa; Zaina, Silvio; Sabanero, Myrna; Daza-Benítez, Leonel; Malacara, Juan Manuel; Barbosa-Sabanero, Gloria

    2016-07-01

    Although ghrelin in cord blood has been associated to birth weight, its role in fetal and postnatal growth has not been elucidated. The aim of this study was to analyze total ghrelin, acyl ghrelin (AG), and des-acyl ghrelin (DAG) in cord blood of newborns with idiopathic birth weight alterations, and to evaluate protein expression of placental GHS-R1, in order to investigate their correlation with birth weight and placental weight. We performed a cross-sectional comparative study in umbilical cord blood and placentas from healthy mothers of SGA, AGA, and LGA (small, adequate and large for gestational age) term newborns (n = 20 per group). Cord blood total ghrelin, AG, and DAG were measured by ELISA, and placental GHS-R1 expression was evaluated by Western blot. Cord blood DAG was higher in SGA compared to AGA newborns (902.1 ± 109.1 and 597.4 ± 58.2 pg/ml, respectively, p = 0.01) while LGA and AGA showed similar values (627.2 ± 76.4 pg/ml for LGA, p = 0.80). DAG negatively correlated with birthweight (r = -0.31, p = 0.02) and placental weight (r = -0.33, p = 0.02). No differences in AG or total ghrelin were found. GHS-R1 protein in placenta was not differentially expressed among SGA, AGA, and LGA. Our results suggest a role of DAG in intrauterine growth. Further studies are needed in order to elucidate the mechanisms by which DAG participates in fetal growth.

  6. Exploratory Study of Total and Free Prednisolone Plasma Exposure and Cushingoid Appearance, Quality of Life and Biochemical Toxicity in Adult Male Kidney Transplant Recipients

    DEFF Research Database (Denmark)

    Bergmann, Troels K; Isbel, Nicole M; Ostini, Remo

    2015-01-01

    associated with free prednisolone plasma exposure with a Spearman correlation coefficient of 0.30 (p value 0.02). The correlation coefficient was 0.24 (p value 0.08) for neck to upper arm circumference ratio and free prednisolone plasma exposure. The clinical Cushingoid phenotype as determined by the Visual...... of 54 years and median time post-transplantation of 75 months. Median prednisolone dose was 5 mg. Mean area under the plasma concentration-time curve was 239